BILIRUBIN MEABOLISM & JAUNDICE and liver failure

bilirubin metabolism

1. Bilirubin metabolism Bilirubin metabolism
and jaundice and and jaundice and
Hepatic Failure Hepatic Failure
DR. VIJAYTA MODIDR. VIJAYTA MODI
ASSO. PROF.ASSO. PROF.
DEPTT. OF PATHOLOGYDEPTT. OF PATHOLOGY

2. Pathophysiological importance of
bilirubin metabolism
 Bilirubin is the end product of heme degradation.
Serum bilirubin level is an important clinical marker of hepatobiliary excretory
function.
Hepatic uptake, storage, conjugation and excretion of bilirubin are finely balanced.
.

3. Erythroid Non-erythroid
Normal:
Senescent erythrocytes
Free heme
Abnormal:Abnormal:
• Hemolysis:
Extravascular
Intravascular
• Ineffective erythropoiesis
(80%) (20%)(80%) (20%)
• CytochromesCytochromes
• CatalaseCatalase
• PeroxidasePeroxidase
• Tryptophane pyrrolaseTryptophane pyrrolase
• MyoglobinMyoglobin
Sources of bilirubinSources of bilirubin

4. Conjugation with glucuronic acid
makes bilirubin water soluble

5. Normal bilurubin production and Normal bilurubin production and
metabolismmetabolism

7. What is jaundice?What is jaundice?
It is yellowish
discoloration of Skin,
mucous membranes,
sclera.. Due to excess
plasma bilirubin.

9. Signs and symptoms Signs and symptoms
Skin and sclerae - yellow
Stool - light colour, clay coloured
Dark urine
Pain in abdomen
Itching
Trouble with sleeping
Fatigue, swelling
Ascites
Mental confusion, coma
Bleeding

10. Types of jaundiceTypes of jaundice
category definition
Pre-hepatic/ hemolyticThe pathology is occurring prior
to the liver.
Hepatic/ hepatocellularThe pathology is located within
the liver.
Post-Hepatic/
cholestatic
The pathology is located after
the conjugation of bilirubin in
the liver.

12. Prehepatic jaundicePrehepatic jaundice
Pre-hepatic jaundice is caused by anything which
causes an increased rate of hemolysis.
In jaundice secondary to hemolysis, the
increased production of bilirubin, leads to the
increased production of urine-urobilinogen.
Bilirubin is not usually found in the urine because
unconjugated bilirubin is not water-soluble.
Note – not so much quantity of enzyme required
for conjugation is available -- increased
unconjugated bilirubin.

13. Hepatocellular jaundiceHepatocellular jaundice
 Cell necrosis reduces the liver's ability to
metabolize and excrete bilirubin leading to a
buildup of unconjugated bilirubin in the blood.
 Other causes include primary biliary cirrhosis
 leading to an increase in plasma conjugated
bilirubin because there is impairment of
excretion of conjugated bilirubin into the bile.

14. Posthepatic jaundicePosthepatic jaundice
 is caused by an interruption to the drainage
of bile in the biliary system
In complete obstruction of the bile duct, no
urobilinogen is found in the urine, since bilirubin
has no access to the intestine and it is in the
intestine that bilirubin gets converted to
urobilinogen to be later released into the
general circulation.

15. Pre-hepatic jaundice Hepatic jaundice Post-hepatic jaundice
Causes
Due to increase in RBCs
breakdown due to
hemolytic anemia.
The rate of RBCs lysis
and bilirubin production
more than ability of liver
to convert it to the
conjugated form
Occur in:
Erythroblastosis fetalis
Hemolytic anemia
Transfusion reaction
Due to liver cell damage
(cancer, cirrhosis or hepatitis)
Conjugation of bilirubin
decreased (ID.Bil. ).
Blilirubin that is conjugated is
not efficiently secreted into bile
but leaks to blood (D.Bil. )
Occur in :
Cirrhosis (scarring of the
liver)
Hepatitis
Gilbert's syndrome
Crigler Najjar syndrome
Due to obstruction of bile
duct which prevents passage
of bilirubin into intestine.
D.Bil will back to liver
and then to circulation
elevating its level in blood
and urine.
Occur in:
Biliary stricture
Cancer of the pancreas or
gallbladder
Gallstones
Dubin- Johnson syndrome
 Rotor’s syndrome
Type of Bil. ID.Bil > D.Bil D.Bil, ID.Bil, T.Bil all (High)D.Bil (High)
Conformational
test
K
+
( High)
Hematology:
CBC (low Hb)
ALT, AST (High) ALP ( High)
hemolytic hemolytic
jaundicejaundice
hepatocellular hepatocellular
jaundicejaundice
obstructive obstructive
jaundicejaundice

16. Differential diagnosis Differential diagnosis

17. Definition of Hyperbilirubinemia
Refers to the increased level of
accumulated bilirubin in the blood &
characterized by jaundice.
Normally there is balance between the
destruction of RBCs and secretion of it’s
products
Kareem AL-Khafajy

18. Causes of Hyper bilirubinemia:
1.physiologic (developmental)
factors such as, prematurity.
2. An association with breast-feeding
or breast milk.
3. Excess production of bilirubin e.g.
hemolytic disease.
4. Disturbed capacity of the liver to secrete
conjugated bilirubin, e.g. enzyme
deficiency, bile duct obstruction.

19. Complications of hyperbilirubinemia:
Unconjugated bilirubin is highly toxic to
neurons.
sever damage of the brain, which occurs
when the serum concentrations reaches
toxic levels & crosses the blood-brain
barrier in the newborn causing
irreversible brain damage.

20. Signs of bilirubin encephalopathy:
Rigid extension of all limbs
Lethargic
Poor feeding
Irritability
Cry
Seizures
Discoloration of skin and eyes

22. LIVER FAILURE

23. Large part of liver damaged beyond repair and
liver no longer able to work
Hepatitis B, C
Long term alcohol consumption
Cirrhosis of liver
Malnutrition
Acetaminophen
Ingestion of poison
Hepatocellular carcinoma
Causes and risk factor

24.  FULMINANT HEPATIC FAILURE -Encephalopathy
starts within 8 weeks
 ACUTE LIVER FAILURE -(ALF) is a rare condition
characterized by the abrupt onset of severe liver
injury.
LATE ONSET HEPATIC FAILURE – subacute FHF
CHRONIC DECOMPENSATED HEPATIC FAILURE –
over six month latent period
TYPES OF LIVER FAILURE 

25. ALF
 Acute liver failure is loss of
liver function that occurs
rapidly — in days or weeks —
usually in a person who has no
pre-existing liver disease .
 It's a medical emergency that
requires hospitalization .

26. C/M OF ALF
Hepatic encephalopathy (mental
confusion, difficulty concentrating and
disorientation)
 Sudden jaundice .
 Pain and tenderness in the upper right
side of the stomach.
 Nausea.
 Vomiting.
 Melena.

27. Ascites (accumulation of fluid in
the stomach)
Ankle Edema (accumulation of
fluid in the legs, ankles and feet)
Feeling ill (Malaise).
Drowsiness.
Muscle tremors.

28. Complications of Hepatic
failure
1 Hepatic encephalopathy
2 Jaundice
3 Foetor hepaticus – due to failure of the liver to
detoxify sulfur containing substances
4 Hepatopulmonary syndrome leads to pulmonary
dysfunction and clubbing
5 Gynaecomastia due to endocrine changes
6 Skin changes- Spider naevi – radiating small vessels
7 Hepatorenal syndrome – Renal failure
8 Testicular atrophy – due to endocrine changes
9 Coagulopathy

30. competencies
1 Describe bilirubin metabolism, enumerate the
etiology and pathologenesis of jaundice,
distinguish between direct and indirect
hyperbilirubinemia
2 Describe the pathophysiology and pathologic
features seen in hepatic failure and their clinic
manifestations, complications and consequences

31. Thank
you