Liver disease Gastrointestinal course hepatic
ritakhater2
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Mar 02, 2025
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About This Presentation
Gastrointestinal course hepatic
Slide Content
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels of
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels ofdisease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
WITH
LIVER DISEASE
APPROACH TO THE PATIENT
WITH
LIVER DISEASE
•A diagnosis of liver disease usually can be
made accurately by a
–careful history
–physical examination
–application of a few laboratory tests
–radiologic examinations
–Liver biopsy considered the standard in evaluation
of liver disease
Loading…
•The liver is the largest organ of the body,
weighing 1–1.5 kg and representing 1.5–2.5%
of the lean body mass.
•It receives a dual blood supply;
–20% of the blood flow from the hepatic artery
–80% from the portal vein
Liver structure and function
•The majority of cells in the liver are
hepatocytes, which constitute 2/3 of the mass
of the liver.
•The remaining cell types are
–Kupffer cells
–Stellate cells
–endothelial cells
–blood vessels, bile ductular cells, and supporting
structures.
Loading…
Liver structure and function
•Hepatocytes perform numerous and vital roles
in maintaining homeostasis and health. These
functions include the
–synthesis of most essential serum proteins
–production of bile and its carriers
–regulation of nutrients
–metabolism and conjugation of lipophilic
Liver structure and function
•The most commonly used liver “function” tests
are measurements of
–serum bilirubin: measure of hepatic conjugation
and excretion
–albumin, and prothrombin time. measures of
protein synthesis.
Liver Diseases
•there are many causes of liver disease they
generally present clinically in a few distinct
patterns, classified as
–Hepatocellular
–cholestatic
–mixed.
Liver Diseases
–In hepatocellular diseases predominate features of
•liver injury
•Inflammation
•necrosis.
–In cholestatic diseases; features of inhibition of
bile flow predominate.
–In a mixed pattern, features of both hepatocellular
and cholestatic injury are present
Liver Diseases
•The pattern of onset and prominence of
symptoms can rapidly suggest a diagnosis,
particularly if major risk factors are considered
such as
–the age of the patient
–sex of the patient
–history of exposure
Liver Diseases
•Typical presenting symptoms of liver disease
include
–Jaundice
–fatigue
–itching
–right upper quadrant pain
–nausea, poor appetite
–abdominal distention
–intestinal bleeding.
Loading…
Liver Diseases
•many patients are diagnosed with liver disease
–who have no symptoms
–who have been found to have abnormalities in
biochemical liver tests
•Liver tests makes relatively simple to
demonstrate the presence of liver injury as well
as to rule it out
Liver Diseases
•Evaluation of patients with liver disease should
be directed at
–establishing the etiologic diagnosis
–estimating the disease severity (grading)
–establishing the disease stage (staging).
Liver Diseases
•Diagnosis should focus on the
–category of disease such as
•hepatocellular,
•cholestatic,
•mixed injury
–Specific etiologic diagnosis.
–Grading
•active or inactive
•mild, moderate, or severe.
–Staging
•acute or chronic
•early or late
Clinical History
•The clinical history should focus
–on the symptoms of liver disease
•nature
•patterns of onset
•progression
–potential risk factors for liver disease.
Clinical History
•The symptoms of liver disease include
constitutional symptoms such as
–fatigue, weakness, malaise
–nausea, poor appetite,
–abdominal pain, and bloating
–more liver-specific symptoms of
•jaundice, dark urine, light stools,
•itching
•Symptoms can also suggest the presence of
–cirrhosis, end-stage liver disease,
Clinical History
•Fatigue
–is the most common and most characteristic
symptom.
–arises after activity or exercise
–rarely present or severe in the morning after
adequate rest
–often intermittent and variable in severity
•Nausea
–occurs with more severe liver disease
–may accompany fatigue or be provoked by odors
of food or eating fatty foods.
Clinical History
•Right upper quadrant discomfort or ache
–marked by tenderness over the liver area.
–arises from stretching or irritation of Glisson’s
capsule
–Severe pain is most typical of
•gallbladder disease,
•liver abscess,
•severe venoocclusive disease
•Exceptional in acute hepatitis.
•Itching
–occurs with acute liver disease
Clinical History
•Jaundice
–hallmark symptom of liver disease
–most reliable marker of severity.
–rarely detectable with a bilirubin level <2.5
mg/dL).
Clinical History
•Major risk factors for liver disease include
details of:
–Alcohol use
–medications
–Personal habits
–sexual activity
–Travel
–exposure to jaundiced or other high-risk persons
–injection drug use
–Recent surgery or recent transfusion
–accidental exposure to blood or needle stick
Clinical History
•For assessing the risk of viral hepatitis, a
careful history
–sexual activity
–family history of hepatitis, liver disease, and liver
cancer
–History of injection drug use
–Transfusion with blood or blood products
Clinical History
•A history of alcohol intake
–consumption associated with an increased rate of
alcoholic liver disease
•22–30 g per day in women
•33–45 g per day in men.
–patients with alcoholic cirrhosis have much higher
daily intake and drunk excessively for ≥10 years
Clinical History
•Familial causes of liver disease include
–Wilson’s disease
–hemochromatosis
–α1 antitrypsin deficiency
–uncommon inherited pediatric liver diseases.
•severe liver disease in childhood or
adolescence with a family history of liver
disease or neuropsychiatric disturbance:
Wilson’s disease.
Physical Examination
• In many patients, the physical examination is
normal unless the disease is acute or severe
and advanced.
•Typical physical findings in liver disease are
–icterus,, Hepatomegaly, hepatic tenderness,
Splenomegaly, Spider angiomata , palmar
erythema,
•Signs of advanced disease include
–muscle wasting, ascites, edema, dilated abdominal
Laboratory Testing
•Blood tests used for initial assessment of liver
disease includes measuring levels ofdisease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.
disease includes measuring levels of
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
–serum alanine and aspartate aminotransferases
(ALT and AST),
–alkaline phosphatase (AlkP),
–direct and total serum bilirubin
–albumin and prothrombin time.
•The pattern of abnormalities generally points to
–hepatocellular versus cholestatic liver disease
Laboratory Testing
•Other laboratory tests:
–γ-glutamyl transpeptidase (gGT)
–hepatitis serology
–autoimmune markers to diagnose
•primary biliary cholangitis (AMA)
•Sclerosing cholangitis (peripheral antineutrophil
cytoplasmic antibody; P-ANCA)
•Autoimmune hepatitis (antinuclear, smooth-muscle, and
liver-kidney microsomal antibody).
Loading…
Diagnostic Imaging
•There are many modalities available for
imaging the liver. US, CT, and MRI
•US and CT have a high sensitivity for detecting
biliary duct dilatation
•All three modalities can detect a fatty liver
•MRCP and ERCP are the procedures of choice
for visualization of the biliary tree.
Diagnostic Imaging
•Elastography measure hepatic stiffness as a
means of assessing hepatic fibrosis.
•Interventional radiologic techniques allow
–biopsy of solitary lesions
–performance of radiofrequency ablation and
chemoembolization of cancerous lesions
–insertion of drains into hepatic abscess
–measurement of portal pressure
–creation of vascular shunts in patients with portal
Liver Biopsy
•standard in the evaluation of patients with liver
disease
•liver biopsy is necessary for diagnosis but is
more often useful in
–assessing the severity (grade) and stage of liver
damage
–predicting prognosis
–monitoring response to treatment.
•Noninvasive means of assessing disease
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Diagnosis of Liver Disease
Important Diagnostic Tests in Common Liver
Diseases
Grading and Staging of Liver
Disease
•Grading refers to an assessment of the severity
or activity of liver disease, whether
•acute or chronic
•active or inactive
•mild, moderate, or severe.
•Liver biopsy is the most accurate means of
assessing
–severity particularly in chronic liver disease.
–Stage of disease as early or advanced, precirrhotic,
and cirrhotic
Grading and Staging of Liver
Disease
Grading and Staging of Liver
Disease
•Cirrhosis can also be staged clinically; Child-
Pugh classification with a scoring system of 5–
15:
–scores of 5 and 6 being Child-Pugh class A
“compensated cirrhosis”
–scores of 7–9 indicating class B
–10–15 indicating class C
Liver Diseases
•Inherited hyperbilirubinemia
–Gilbert’s syndrome
–Crigler-Najjar syndrome, types I and II
–Dubin-Johnson syndrome
–Rotor syndrome
•Viral hepatitis
–Hepatitis A
–Hepatitis B
–Hepatitis C
–Hepatitis D
Liver Diseases
•Immune and autoimmune liver diseases
–Primary biliary cholangitis
–Autoimmune hepatitis
–Sclerosing cholangitis
–Overlap syndromes
–Graft-versus-host disease
–Allograft rejection
•Genetic liver diseases
–Antitrypsin deficiency
Liver Diseases
•Alcoholic liver disease
–Acute fatty liver
–Acute alcoholic hepatitis
–Cirrhosis
•Nonalcoholic fatty liver
–Steatosis
–Steatohepatitis
•Acute fatty liver of pregnancy
Liver Diseases
•Liver involvement in systemic diseases
–Sarcoidosis
–Amyloidosis
–Glycogen storage diseases
–Celiac disease
–Tuberculosis
–Mycobacterium avium intracellulare
Liver Diseases
•Cholestatic syndromes
–Benign postoperative cholestasis
–Jaundice of sepsis
–Total parenteral nutrition (TPN)-induced jaundice
–Cholestasis of pregnancy
–Cholangitis and cholecystitis
–Extrahepatic biliary obstruction (stone, stricture,
cancer)
–Biliary atresia
–Caroli’s disease
–Cryptosporidiosis
Liver Diseases
•Drug-induced liver disease
–Hepatocellular patterns (isoniazid, acetaminophen)
–Cholestatic patterns (methyltestosterone)
–Mixed patterns (sulfonamides, phenytoin)
–Micro- and macrovesicular steatosis (methotrexate,
fialuridine)
•Vascular injury
–Venoocclusive disease
–Budd-Chiari syndrome
Liver Diseases
•Mass lesions
–Hepatocellular carcinoma
–Cholangiocarcinoma
–Adenoma
–Focal nodular hyperplasia
–Metastatic tumors
–Abscess
–Cysts
–Hemangioma
EVALUATION OF LIVER
FUNCTION
EVALUATION OF LIVER
FUNCTION
•Several biochemical tests are useful in the
evaluation and management of patients with
hepatic dysfunction.
•These tests can be used to
–(1) detect the presence of liver disease,
–(2) distinguish among different types of liver
disorders
–(3) gauge the extent of known liver damage
–(4) follow the response to treatment
EVALUATION OF LIVER
FUNCTION
•Liver tests can be normal in patients with
serious liver disease and abnormal in patients
with diseases that do not affect the liver.
•Liver tests rarely suggest a specific diagnosis;
rather, they suggest a general category of liver
disease, such as hepatocellular or cholestatic.
•The liver carries out thousands of biochemical
functions, laboratory tests measure only a
limited number of these functions
•aminotransferases or alkaline phosphatase, do
not measure liver function at all
EVALUATION OF LIVER
FUNCTION
•Tests usually employed in clinical practice
include
–Bilirubin
–Aminotransferases
–alkaline phosphatase
–Albumin
–prothrombin time.
EVALUATION OF LIVER
FUNCTION
•Tests Based on Detoxification And
excretory Functions
•Tests that Measure Biosynthetic Function of
the Liver
•Coagulation Factors
•Other Diagnostic Tests
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
•Blood ammonia
•Serum enzymes
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Bilirubin, a breakdown product of the porphyrin
ring of heme-containing proteins, is found in the
blood in two fractions—conjugated and
unconjugated.
•The unconjugated fraction, also termed the indirect
fraction , is insoluble in water and is bound to albumin
in the blood.
•The conjugated (direct) bilirubin fraction is water
soluble and can therefore excreted by the kidney.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–Elevation of the unconjugated fraction of bilirubin
is rarely due to liver disease.
–An isolated elevation of unconjugated bilirubin is
seen
•in hemolytic disorders
•in a number of genetic conditions such as Griggler-
Najjar and Gilbert’s syndromes.
Tests Based on Detoxification And
excretory Functions
•Serum bilirubin
–conjugated hyperbilirubinemia almost always
implies liver or biliary tract disease.
–In most liver diseases, both conjugated and
unconjugated fractions of the bilirubin tend to be
elevated.
–degree of elevation of the serum bilirubin is
important in a number of conditions
•In viral hepatitis, the higher the serum bilirubin, the
greater the hepatocellular damage.greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
greater the hepatocellular damage.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
•Total serum bilirubin correlates with poor outcomes in
alcoholic hepatitis
Tests Based on Detoxification And
excretory Functions
•Blood ammonia
–The liver plays a role in the detoxification of
ammonia by converting it to urea,
–Some physicians use the blood ammonia for
detecting encephalopathy
or
–for monitoring hepatic synthetic function
–There is very poor correlation between
•the presence or the severity of acute encephalopathy and
elevation of blood ammonia;
Tests Based on Detoxification And
excretory Functions
•Serum enzymes
can be grouped into three categories:
–(1) enzymes whose elevation in serum reflects
damage to hepatocytes
–(2) enzymes whose elevation in serum reflects
cholestasis
–(3) enzyme tests that do not fit precisely into either
pattern
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–The aminotransferases are sensitive indicators of
liver cell injury and in recognizing acute
hepatocellular diseases
–They include the
•aspartate aminotransferase (AST)
•alanine aminotransferase (ALT).
–AST is found in the liver, cardiac muscle, skeletal
muscle, kidneys, brain, pancreas, lungs,
leukocytes, and erythrocytes in decreasing order of
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
–elevation of the aminotransferases is of no
prognostic significance in acute hepatocellular
disorders.
•up to 300 U/L are nonspecific and found in any liver
disorder
•Aminotransferases >1000 U/L occur almost exclusively
in disorders associated with extensive hepatocellular
injury
–(1) viral hepatitis,
–(2) ischemic liver injury
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect damage to hepatocytes
•AST/ALT < 1
–chronic viral hepatitis
–non-alcoholic fatty liver disease
•AST/ALT > 2/1 is suggestive, while a ratio >3:1 is
highly suggestive of alcoholic liver disease.
–The AST in alcoholic liver disease is rarely >300
IU/L, and the ALT is often normal.
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–three enzymes
•alkaline phosphatase,
•5′-nucleotidase,
•γ-glutamyl transpeptidase (GGT)
–GGT less specific for cholestasis than are
elevations of alkaline phosphatase or 5′-
nucleotidase
–alkaline phosphatase consists of many distinct
isoenzymes found in the liver; bone; placenta; and,
Tests Based on Detoxification And
excretory Functions
•Enzymes that reflect cholestasis
–Elevation alkaline phosphatase less than threefold
can be seen in almost any type of liver disease.
–Alkaline phosphatase elevations greater than four
times normal
•cholestatic liver disorders,
•infiltrative liver diseases such as cancer and
amyloidosis,
•bone conditions
Tests that Measure Biosynthetic
Function of the Liver
–Serum albumin
–Serum globulins
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–synthesized by hepatocytes.
–has a long half-life: 18–20 days, with ∼4%
degraded per day.
–not a good indicator of acute or mild hepatic
dysfunction
–minimal changes in the serum albumin are seen in
•viral hepatitis,
Tests that Measure Biosynthetic
Function of the Liver
•Serum albumin
–Hypoalbuminemia is more common in chronic
liver disorders
–hypoalbuminemia is not specific for liver disease
may occur in
•protein malnutrition
•protein-losing enteropathies
•nephrotic syndrome
•chronic infections
Tests that Measure Biosynthetic
Function of the Liver
•Serum globulins
–group of proteins made up of
• γ globulins (immunoglobulins) produced by B
lymphocytes
•α and β globulins produced primarily in hepatocytes.
–γ Globulins are increased in chronic liver disease.
–Increases in the concentration of isotypes of γ
globulins are helpful in the recognition of certain
chronic liver diseases.
•increases in IgG levels are common in autoimmune
Coagulation Factors
–the blood clotting factors are made exclusively in
hepatocytes (except factor VIII)
–serum half lives ranging from 6 h for factor VII to
5 days for fibrinogen
–The prothrombin time may be elevated
•in hepatitis and cirrhosis
•in vitamin K deficiency
–obstructive jaundice
–fat malabsorption
Other Diagnostic Tests
–Percutaneous liver biopsy
–Liver biopsy is of proven value in the following
situations:
•(1) hepatocellular disease of uncertain cause
•(2) prolonged hepatitis with the possibility of chronic
active hepatitis
•(3) unexplained hepatomegaly
•(4) unexplained splenomegaly,
•(5) hepatic filling defects by radiologic imaging
•(6) fever of unknown origin
•(7) staging of malignant lymphoma.
Other Diagnostic Tests
Ultrasonography
–the first diagnostic test to use in patients whose
liver tests suggest cholestasis.
–shows space-occupying lesions within the liver,
–with Doppler imaging can detect the patency of the
portal vein, hepatic artery, and hepatic veins and
the direction of blood flow.
THE HYPERBILIRUBINEMIAS
•Bilirubin metabolism
–Bilirubin is the end product of heme degradation.
–70–90% of bilirubin is derived from degradation of
the hemoglobin of senescent red blood cells.
hepatocellular bilirubin transport
•Transfer of bilirubin
from blood to bile
involves four distinct
but interrelated steps
–Hepatocellular uptake
–Intracellular binding
–Conjugation
–Biliary excretion
Disorders of Bilirubin Metabolism
Leading to Unconjugated Hyperbilirubinemia
•Increased Bilirubin Production
–Hemolysis
–Ineffective erythropoiesis
•Decreased Hepatic Bilirubin Clearance
–Decreased hepatic uptake
–Impaired conjugation
•Physiologic neonatal jaundice
•Acquired conjugation defects
•Hereditary Defects in Bilirubin Conjugation
–Crigler-Najjar syndrome, type I
–Crigler-Najjar syndrome, type II
Disorders of Bilirubin Metabolism Leading to Mixed or
Predominantly Conjugated Hyperbilirubinemia
•Familial Defects in Hepatic Excretory
Function
–Dubin-Johnson syndrome
–Rotor syndrome
–Benign recurrent intrahepatic cholestasis
–Progressive familial intrahepatic cholestasis
ACUTE VIRAL HEPATITIS
Acute viral hepatitis
•Acute viral hepatitis is a systemic infection
affecting the liver predominantly.
•Almost all cases of acute viral hepatitis are
caused by one of five viral agents:
–Hepatitis A virus (HAV)
–hepatitis B virus (HBV)
–hepatitis C virus (HCV)
–the HBV-associated delta agent or hepatitis D virus
(HDV)
–hepatitis E virus (HEV).
Virology and etiology
Hepatitis A
•Non enveloped 27-nm, heat-, acid-, and ether-
resistant RNA virus in the Hepatovirus genus
of the picornavirus family
•Inactivation of viral activity can be achieved by
– boiling for 1 min
–contact with formaldehyde and chlorine
–ultraviolet irradiation.
•Hepatitis A has an incubation period of ∼4
weeks.
•Its replication is limited to the liver, but the
virus is present in the liver, bile, stools, and
HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)HEPATITIS A (Infectious Hepatitis)
Oral
acquisition
Cross
intestines
Enter blood
stream
Parenchymal cells
of liver
(hepatocytes &
Kupffer’s cells)
Released into
bile
Excreted in
stool
•Antibodies to HAV (anti-HAV) can be detected
during acute illness when serum
aminotransferase activity is elevated and fecal
HAV shedding is still occurring.
•This early antibody response is predominantly
of the IgM class and persists for several
months, rarely for 6–12 months.
•During convalescence, however, anti- HAV of
the IgG class becomes the predominant
antibody.
•Therefore, the diagnosis of hepatitis A is made
Scheme of typical clinical and
laboratory features of hepatitis A.
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