Jaundice and Cholestasis: Pathophysiology.pptx

jaundice pathology

1. JAUNDICE AND CHOLESTASIS Under guidance of : dr a.k.khnara h.o.d . of pathology MHMCH Presented by : Nilanjana Guha, 3 rd year

2. What is it? Jaundice – it is a pathophysiological condition characterised by yellow pigmentation of the skin , sclarae or mucous membrane by bilirubin as a result of hyperbilirubinaemia due to * overproduction of bilirubin * hepatitis * obstruction of bile flow cholestasis – this is a condition of systemic retention of bile as well as other solutes which eliminates through bile .

3. Normal serum bilirubin concentration is 0.2-0.8 mg/ dL Clinical evidence of jaundice seen when serum bilirubin concentration exceeds 2mg/ dL . level may increase upto 30-40mg/ dL with severe diseased condition . Latent - more than normal and less than 2mg/ dL bilirubin concentration is not a visible condition, can be detected by serum analysis.

4. Physiology of bilirubin production bilirubin metabolism Glutathione s transferase Uridin diphospho glucorunosyl transferase

5. Pathophysiology of jaundice Unconjugated bilirubin Insoluble in water at physiologic pH. It is alcohol soluble & non toxic Exists in tight complexes with serum albumin [ very small amount present as albumin free anion in plasma causing kernicterus in newborns ] Cannot be excreted through urine even when blood levels are high – not filtered by glomerulus No covalent bond with albumin Conjugated bilirubin Water soluble & non toxic Weak association with albumin Excreted in urine Bilirubin-albumin covalent bond formed.which is termed as bilirubin delta fraction

6. So jaundice may result when the equilibrium between bilirubin production and clearance is disturbed by one or more of the following results :- Extrahepatic excessive production of bilirubin Reduced hepatocyte uptake of unconjugated albumin-bilirubin Impaired hepatic conjugation Based on these mechanisms, the pathogenesis and main features of two predominant form of jaundice are discussed . Decreased hepatocellular excretion of bilirubin into bile Impaired bile flow

7. Causes of jaundice predominantly unconjugated hyperbilirubinaemia

8. FEATURES OF UNCONJUGATED HYPERBILIRUBINEAMIA HEMOLYTIC TYPE Hyperbilirubineamia of unconjugated type ( as capacity of the liver to conjugate large amount of bilirubin is exceeded ) Normal serum transaminase Normal alkaline phosphatase Normal serum proteins Bile pigment being unconjugated type is absent in urine Fecal matter become dark brown due to over excretion of bilepigments

9. PREDOMINANTLY CONJUGATED HYPERBILIRUBINEAMIA(CHOLESTASIS) causes of intrahepatic cholestasis

10. Conjugated hyperbilirubineamia Bilirubinuria Elevated serum bile level and constant pruritus Elevated serum alkaline phosphate Hyperlipidaemia Hypoprothrombinaemia Elevated serum transaminase(in Pure cholestasis at advanced stage) biopsy : elongated green brown bileplug in the canaliculi of hepatocyte at the periphery of the lobule . canalicular bile stasis causes interlobular ductules followed by periportal fibrosis Features of intrahepatic cholestasis

11. Causes of extra hepatic cholestasis (mainly from mechanical biliary obstruction)

12. Features of extrahepatic cholestasis(obstructive jaundice) Conjugated hyperbilirubineamia,elevated bile acids these are all same as intrahepatic cholestasis. Malabsorption of fat soluble vitamins Steatorrhoea reduced fat absorbtion Prolonged prothrombin time due to hypoprothrombineamia ( cannot be checked by vit k administration) Clay colored stool Fever due to ascending bacterial biopsy : bile lakes due to rupture of canaliculi in infection hepatocytes in centrilobular area(obstruction in ext hep duct>dilatation>rupture )

13. Unconjugated Prematurity jaundice or icterus neonatarum HDN & kernicterus Congenital haemolytic disorders Perinatal complications i.e haemorrhage Hereditary i.e Gilbert’s syndrome, Crigler-najjar syndrome( Type I or Type II) Conjugated Hereditary i.e Dubin-johnson syndrome,Rotor’s syndrome Infection ( HBV,HCV,Rubella,syphilis , herpes simplex) Metabolic disorders Galactoceamia 1-antitrypsin deficiency Cystic fibrosis Idiopathic i.e neonatal hepatitis,congenital hepatic fibrosis Biliary atresia Reye’s syndrome

14. Some discussion on the above conditions 1.HEMOLYTIC DISEASE OF NEONATES Due to Rh incompatibility or ABO invcompatibility . Results from the passage of IgG antibodies from the maternal circulation across the placental barrier into foetal RBCs . Rh 1.Severe- intra-uterine death from hydrops foetalis / 2. Severe anaemia and jaundice Unconjugated bilirubin >20mg/dl Results into deposition of bile in basal ganglia i.e KERNICTERUS ABO frequently seen in group O mothers.who possesses anti A anti B antibody of IgG class . ( IgM class antibodies cannot cross placenta )

15. 2.CONGENITAL HEMOLYTIC DISORDERS In HEREDITARY SPHEROCYTOSIS (defect In protein which binds the lipid to the cytoskeleton) jaundice occurs due to Increased concentration of bilirubin in plasma And pigment gallstones also occur due to increased bile pigment production. 3.GILBERT’S SYNDROME Hereditary non hemolytic Autosomal dominant type Unconjugated because UDP- glucuronosyl transferase activity is reduced Mild jaundice <5mg/dl Prognosis excellent Biopsy : normal except some increased lipofuschin

16. 4 . Crigler-Najjar syndrome This is a rare familial non-haemolytic jaundice with very high unconjugated hyperbilirubineamia . This is of two types- Type I Autosomal recessive Complete absence of UDP- glucuronosyl transferase Bilirubin >20mg/ dl.results kernicterus Poor prognosis Morphologically mild canalicular stasis, otherwise normal Type II Autosomal dominant UDP- glucuronosyl transferase level less Bilirubin <20mg/dl Prognosis good, pt responds in treatement

17. 5.Conjugated non haemolytic hereditary disorders Dubin-johnson syndrome Autosomal recessive type Conjugated due to defect in canalicular excretion( prolonged BSP excretion test ) Bilirubin <5mg/dl Prognosis excellent Biopsy : hepatocytes show greenish black pigment neither iron nor bile B.Rotor’s syndrome Autosomal recessive type Conjugated due to deranged hepatic storage Bilirubin level- <5mg/dl Excellent prognosis

18. 6.Metabolic Disorders

19. The following are the key elements of the recommendations provided by this guideline for management Promote and support successful breastfeeding . Establish nursery protocols for the identification and evaluation of hyperbilirubinemia . Measure the total serum bilirubin ( TSB ) or transcutaneous bilirubin ( TcB ) level on infants jaundiced in the first 24 hours . Interpret all bilirubin levels according to the infant’s age in hours. Recognize that infants at less than 38 weeks’ gestation , particularly those who are breastfed, are at higher risk of developing hyperbilirubinemia and require closer surveillance and monitoring. Perform a systematic assessment on all infants before discharge for the risk of severe hyperbilirubinemia . Provide appropriate follow-up based on the time of discharge and the risk assessment. Treat newborns , when indicated, with phototherapy or exchange transfusion.

20. Some other conditions where jaundice may develop : Pregnancy - Intrahepatic cholestasis of pregnancy Viral hepatitis Acute fatty liver of pregnancy Immune system- GVH disease Infection- Cytomegalovirus(jaundice associated with splenomegaly Babesia macroti protozoa

21. D/D OF JAUNDICE

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