lft ppt and parameters of lft with fate of bilirubin.pptx

lft parameters and their signicficane

1. LIVER FUNCTION TEST PRESENTED BY- DR.AYUSHI AGARWAL GUIDED BY- DR. AMBRISH KUMAR SIR

2. Liver is the largest and most complex internal organ of the body. The weight of liver is about 1.5kg. It is located below the diaphragm in the right upper quadrant of the abdominal cavity. All blood flows from intestine and pancreas and reaches liver via portal venous system.

3. FUNCTIONS OF LIVER • Liver is a multifunctional organ that is involved in diverse body functions. Metabolic Functions Liver actively participates in carbohydrate metabolism, lipid, protein, mineral and vitamin metabolisms. Excretory Functions Bile pigments, bile salts and cholesterol are excreted in bile into intestine. Protective functions & detoxification Kupffer cells of liver perform phagocytosis to eliminate foreign compounds. For example ammonia is detoxified to urea and metabolism of xenobiotics (detoxification). Clearance of hormones such as insulin, parathyroid hormone, oestrogen, cortisol.

4. 4. Hematological and synthetic functions Liver participates in formation of blood (particularly in embryo) Synthesis of plasma proteins(albumin and prothrombin), hormones e.g angiotensinogen, insulin-like growth factor and triiodothyronine. Destruction of erythrocytes (Bilirubin). 5. Storage functions- Glycogen, vitamins A, D and B 12. 6. Production of bile salts- Helps in digestion.

5. Liver Function Tests (LFTs) • It is a non-invasive methods for screening of liver dysfunction • Help inidentifying general types of disorder • Assess severity and allow prediction of outcome • Disease and treatment follow up.

6. LIVER FUNCTION TESTS LIST- TOTAL BILURUBIN AND DIRECT AND INDIRECT FRACTION ALANINE AMINOTRANSFERASE(ALT) ASPARTATE AMINOTRANSFERASE(AST) ALKALINE PHOSPHATASE(ALP) GAMMA GLUTAMYL TRANSPEPTIDASE(GGPT) 5' NUCLEOTIDASE(5'NT) SERUM ALBUMIN PROTHROMBIN TIME

7. Classification of LFTs Liver function tests are broadly classified into following groups according to their functions:- Group I —Tests of hepatic excretory function i. Serum—Bilirubin; total, conjugated, and unconjugated. ii. Urine—Bile pigments, bile salts Group II—Markers of liver injury i. Alanine amino transferase (ALT) ii. Aspartate amino transferase (AST) iii. Alkaline phosphatase (ALP) iv. Gamma glutamyl transferase (GGT)

8. Group III—Tests for synthetic function of liver i. Total proteins ii. Serum albumin, globulins, A/G ratio iii. Prothrombin time

9. 1. BILIRUBIN:- A by-product of red blood cell breakdown. It is conjugated by the liver to form bilirubin diglucuronide and excreted through bile. It is the yellowish pigment observed in jaundice • High bilirubin levels are observed in: – Gallstones, acute and chronic hepatitis

10. PLASMA BILIRUBIN:- • Normal plasma bilirubin: 0.2–0.8mg/dl. • Unconjugated bilirubin: 0.2–0.6mg/dl. • Conjugated bilirubin: 0–0.2mg/dl. If the plasma bilirubin level exceeds 1mg/dl, the condition is called hyperbilirubinemia. • Levels between 1 & 2 mg/dl are indicative of latent jaundice. • When the bilirubin level exceeds 2mg/dl, it diffuses into tissues producing yellowish discoloration of sclera, conjunctiva, skin & mucous membrane resulting in jaundice.

11. TESTS BASED ON SYNTHETIC FUNCTION OF LIVER 1.SERUM ALBUMIN • The most abundant protein synthesized by the liver • Normal serum levels: 3.5–5g/dL. • Synthesis depends on the extent of functioning liver cell mass • Longer half-life: 20days • Its levels decrease in all chronic liver diseases.

12. 2.SERUM GLOBULIN • Normal serum levels: 2.5–3.5g/dL • α and β-globulins mainly synthesized by the liver. • They constitute immunoglobulins(antibodies) • High serum γ-globulins are observed in chronic hepatitis and cirrhosis: – IgG in autoimmune hepatitis – IgA in alcoholic liver disease

13. 3.Prothrombin- synthesized by the liver, a marker of liver function. • Half-life: 6hrs (indicates the present function of the liver) • Normal ProthrombinTime = 11 to 12 seconds • PT is prolonged only when liver loses more than 80% of its reserve capacity • Vitamin K deficiency also causes prolonged PT • Intake of vitamin K does not affect PT in liver disease

14. 4. α-Fetoprotein (AFP) One of the major plasma proteins in foetal life. In acute hepatic injury AFP ↑ 10 – 20X upper ref limits. About 10% pt’s with viral hepatitis have↑AFP Fibrosis post chronic liver disease, AFP↑ Used to screen and diagnose HCC & hepatoblastoma

15. TESTS BASED ON SERUM ENZYMES 1. ALANINE AMINO TRANSFERASE ALT or SGPT (serum glutamate pyruvate transaminase) ALT is a cytoplasmic enzyme. Normal Range: 10- 35 U/L. The test is primarily used to diagnose liver disease, to monitor the course of treatment for hepatitis, active post necrotic cirrhosis, and the effect of drug therapy. More liver-specific than AST High serum levels in acute hepatitis (300-1000U/L) Moderate elevation in alcoholic hepatitis and non-alcoholic chronic hepatitis (100-300U/L) . Minor elevation in cirrhosis, chronic hepatitis (50-100U/L) 4/22/2020

16. 2. Aspartate Aminotransferase (AST) AST or SGOT (serum glutamate oxaloacetate transaminase) AST is found in both cytoplasm & mitochondria Also reflects damage to the hepatic cell It is less specific for liver disease It may be elevated and other conditions such as a myocardial infarct and muscle disease Normal range: 8–20U/L A marker of hepato cellular damage. High serum levels are observed in: – Chronic hepatitis, cirrhosis and liver cancer

17. 3. Alkaline phosphatase (ALP) • A non-specific marker of liver disease • Produced by bone osteoblasts(for bone calcification) • Present on hepatocyte membrane • Normalrange:40–125U/L Moderate elevation observed in: Infective hepatitis, alcoholic hepatitis and hepatocellular carcinoma. High levels are observed in: – Extrahepatic obstruction (obstructive jaundice) and intrahepatic cholestasis Very high levels are observed in: Bone diseases

18. 4. γ-Glutamyl transpeptidase (GGT) It is a membrane bound glycoprotein which catalyses the transfer of γ- glutamyl group to other peptides and AAS. GGT isused by the body to synthesize glutathione tri peptide. This is a microsomal enzyme widely distributed in body tissues, including liver. Very useful in diagnosis of obstructive jaundice. (not elevated in bone diseases). Normal range: 10–30U/L Moderate elevation observed in: Infective hepatitis and prostate cancers GGT is increased in alcoholics despite normal liver function tests: Highly sensitive to detecting alcohol abuse In liver diseases, GGT elevation parallels that of ALP. In alcoholic liver disease, GGT levels may be parallel to alcohol intake.

19. OTHER TESTS:- • Tests based on metabolic capacity–Galactose tolerance, antipyrine clearance. • Tests based on detoxification - Hippuric acid synthesis. Special tests: Blood ammonia α1- antitrypsin Immunoglobulins Ceruloplasmin

20. Presence of abdominal pain Painful, colicky → Gallstones? Cholangitis? Absence → Cholangiocarcinoma/pancreatic malignancy? Obstructive symptoms Pale stools Dark urine Pruritis Systemic symptoms Fever, chills and rigors → Cholangitis? Biliary sepsis? Hepatitis? History

21. Risk factors for hepatitis Travel history Sexual history Intravenous drug use Risk factors for acute/chronic liver injury Alcohol Paracetamol • Other drugs e.g. amoxicillin, flucloxacillin

22. Icterus Abdominal tenderness (RUQ pain) Organomegaly (hepatomegaly, splenomegaly) Signs of acute liver failure Bruising (coagulopathy) Encephalopathy (asterixis +/- lethargy/confusion) Risk factors Injection marks Tattoo Examination

23. PREHEPATIC (OR ‘HAEMOLYTIC') JAUNDICE Causes Haemolytic anaemia (hereditary spherocytosis/elliptocytosis, sickle cell anaemia, G6PD deficiency, etc.) Gilbert's Syndrome (1 unconjugated bilirubin) Mechanism Excessive haemolysis of red blood cells → Increase in unconjugated bilirubin Increased Conjugation of bilirubin in liver {saturation of enzymes} Increased Urobilinogen → resorbed into circulation → dark urine Increased Stercobilinogen {converted from urobilinogen} → dark stools

24. HEPATIC JAUNDICE Causes Viral hepatitis (A-E) Alcoholic hepatitis Ischemic hepatitis Drug-induced hepatitis (esp. paracetamol) Autoimmune hepatitis Malignancy (primary or secondary) Decompensated chronic liver disease

25. POST-HEPATIC JAUNDICE Causes Any cause of 'cholestatic' or obstructive jaundice: Gallstones Cholangiocarcinoma Pancreatic carcinoma Primary biliary cholangitis (autoimmune) Primary sclerosing cholangitis (associated with ulcerative colitis) Parasites CONJUGATED BILIRUBIN & LIPASE FROM GALLBLADDER →BLOCKED ENTEROHEPATIC CIRCULATION→ PALE, FATTY STOOLS + DARK URINE

26. Liver Cirrhosis It is a chronic, degenerative disease characterized by replacement of normal liver tissue with diffuse fibrosis that disrupts the structure and function of the liver. Types: а. Alcoholic Cirrhosis ( Laennec's Cirrhosis) Most common type of liver cirrhosis Caused by chronic alcoholism b. Postnecrotic cirrhosis Late result of a previous bout of acute viral hepatitis c. Biliary cirrhosis Resulted from chronic biliary obstruction and infection Least common type

27. Early Signs- anorexia, nausea, indigestion aching or heaviness in right upper quadrant weakness & fatigue

28. Late signs: abnormal liver function tests: Nbilirubin (N=0-0.9mg/di),  AST (N=4.8-19U/L)  ALT (N= 2.4-17U/L)  Serum alkaline phosphatase (N=30-40U/L)  Ammonia (plasma) (N= 15-45umol/L) intermittent jaundice, pruritus edema, ascites, prominent abdominal wall veins Ecchymosis, bleeding tendencies Anemia Infection Gynecomastia, testicular atrophy Neurologic changes

29. Complications of Liver Cirrhosis 1. Ascites- abnormal intraperitoneal accumulation of watery fluid containing small amounts of protein. 2. Hepatic Encephalopathy- cerebral dysfunction associated with severe liver disease. Inability of the liver to metabolize substances that can be toxic to the brain such as ammonia, which is produced by the breakdown of protein in the intestinal tract. 3. Esophageal Varices- distention of the smaller blood vessels of the esophagus as a result of portal hypertension - due to obstruction of venous circulation within the damaged liver.