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Can be classified in to

  1. Pre hepatic
    1. RBC membrane defects spherocytosis elliptocytosis
    2. Rbc enzme defects G 6 PD deficiency
    3. Globin chain synthesis defect thalassemias
    4. Acquired hemolysis due to drugs like sulfa penicillin antimalarials 
  2. Hepatic
    1. Neonatal jaundice                                        
    2. Viral hepatitis
    3. Crigler Najjar syndrome                                
    4. Gilberts diseases
    5. Galactosemia                                      
    6. Hypothyroidism
    7. Drugs like novobiocin pregnanediol AKT              
    8. Sepsis
    9. I u Infection like TORCH infection                  
    10. Liver diseases: 
  3. Obstructive post hepatic
    1. Biliary atresia                              
    2. Choledochal cyst
    3. Inspected bile                              
    4. Strictures and calculus in bulkier tree
    5. Alpha 1 antitypic deficiency                  
    6. Drugs
    7. Dublin john sons syndrome                  
    8. Rotor syndrome 

Important points

  1. Aspirin and sulphonamides displace bilirubin from albumin.
  2. Activity of the enzymes UDP glucuronyl-transferase and UDP glucose-6 – phosphate dehydrogenase are not fully developed in the first few days of extrauterine life so indirect hyperbilirubinemia occurs.
  3. Phenobarbitone therapy induces development of the hepatic microsomal enzymes in CrigIer-Naijar syndrome.
  4. In biliary obstruction, bilirubin does not reach the gut so stercobilinogen cannot be formed. This is not reabsorbed in the-blood as urobilinogen
  5. Therefore in obstructive Jaundice urobilinogen is absent in the urine though bilirubin is secreted- Urine is dark color.
  6. In obstructive jaundice plasma cholesterol is elevated. Whenever intestinal concentration of bile salts is decreased, synthesis of cholesterol is increased.
  7. Itching in obstructive jaundice is due to the deposits of bile salts in the skin. 

Table: Inborn Errors of Metabolism that Affect the Liver 

  1. Disorders Of Carbohydrate Metabolosm
    1. Disorders of galactose metabolism
      1. Galactosemia
    2. Disorders of fructose metabolism
      1. Hereditary fructose intolerance (aldolase deficiency)
      2. Fructose -1,6 diphosphatse deficiency
    3. Glycogen storage diseases
      1. Type I Von Glierke (la)
      2. Type 1b
      3. Type III (cori/Forbes)
      4. Type IV(Andersen)
      5. Type VI (Hers)
      6. Congenital disorders of glycosylation (CGD)
  2. Disorders of amind acid and protein metabolosm
    1. Disorders of tyrosine metabolism
      1. Hereditary tyrosinemia (type I)
      2. Tyrosinemia, type II 
    2. Inherited urea cycle enzyme defects
      1. CPS deficiency                      
      2. OTC deficiency (X-linked dominant)
      3. Citrullinemia                        
      4. Argininosuccinic aciduria
      5. Argininemia                  
      6. N-AGS deficiency 
  3. Disorder Of Lipid Metabolism
    1. Wolman disease            
    2. Cholesteryl ester storage disease
    3. Gaucher disease            
    4. Niemann pick type 
  4. Disorders Of Bile Acid Metabolosm
    1. Isomerase deficiency
    2. Reductase deficiency
    3. Zellweger syndrome (cerebrohepatorenal) 
  5. Disorders Of Metal Metabolism
    1. Wilson disease                      
    2. Hepatic copper overload
    3. Indian childhood cirrhosis              
    4. Neonatal iron storage disease (perinatal hemochromatosis) 
  6. Disorders Of Bilirubin Metabolosm
    1. Crigler Najjar                        
    2. Gilbert disease
    3. Dubin Johnson syndrome              
    4. Rotor syndrome 
  7. Miscellaneous
    1. α1 – Antitrypsin deficiency                    
    2. Cystic fibrosis
    3. Erythropoietic protoporphyria                
    4. Citrine deficiency
    5. CPS, Citrine deficiency carbamoyl phosphate synthetase, N- AGS, N- acetyl glutamate synthetase; OTC ornithine transcarbamoylase. 
  1. Unconjugated hyperbilirubinemia – it is defined as the elevation of unconjugated bilirubin of >85% of the total.

The causes are:

  1. Hemolytic disorders Q – In these conditions, serum bilirubin levels are usually less than 4 mg/dl. Increase retic count
  2. Ineffective erythropoiesis – vit B12 and folate deficiency.
  3. Drugs – rifampicin, probenecid, novobiocin, flavispidic acid, cholecystographic agents and ribavirin, by diminishing hepatic uptake of bilirubin.
  4. Genetic disorders (Impaired bilirubin conjugation):-
    1. Gilbert’s syndrome – Due to reduced activity (10-33%) of UDP glucuronyl transferase Q and also due to reduced uptake of bilirubin.
      It is autosomal dominant Q. Serum bilirubin levels are usually ≤ 4 mg/dl. The serum level of bilirubin fluctuate and increase during fasting Q.
      Phenobarbital Q administration normalizes serum bilirubin level. The patients have normal life expectancy Q.
    2. Crigler-Najjar type I – due to complete absence of bilirubin UDP glucuronyl transferase Q activity. It is autosomal recessive Q disorder found in neonates and characterized by severe jaundice (Bilirubin > 20 mg/dl) and kernicterus leading to death in infancy Q.
    3. Crigler-Najjar Type II – Due to reduced activity (0-10% of normal) of UDP glucuronyl transferase Q. It is predominantly autosomal recessive.
      Serum bilirubin levels are in the range of 6-25 mg/dl. The patient usually survive into the adulthood, kernicterus is uncommon but may develop under the surgery or inter current illness.
      Serum bilirubin concentration decreases by >25% in response to enzyme inducers such as Phenobarbital Q.
  5. MISC.- Degradation of hemoglobin in extravascular collection of RBCs like a large hematoma. 

  1. Conjugated hyperbilirubinemia:

It is defined as the elevation of conjugated bilirubin to >15% of total Q. The causes are:

  1. Dubin-Johnson syndrome: It is an autosomal recessive Q disorder due to defect in canalicular transport Q of organic anions because of mutation of MRP2 Q.
    Total bilirubin concentration are typically between 2-5 mg/dl.
    A cardinal feature of Dubin-Johnson syndrome is the accumulation of dark, coarsely granular Q pigment in Q the lysosomes of centrilobular hepatocytes. As a result liver may be grossly black Q.
    The diagnostic tests are:
    → Bromsulphalein excretion (BSP) Q – A characteristic rise in plasma concentration of BSP at 90 min after injection, due to reflux of BSP into the circulation from the hepatocyte.
     Also non-visualization of gallbladder on oral cholecystography Q.
    Patients with Dubin Johnson’s syndrome are usually asymptomatic, and have normal life expectancy.
    Usually no treatment is required.
  2. Rotor syndrome – It is an autosomal recessive Q disorder clinically similar to the Dubin-Johnson syndrome. But, there is no pigmentation in the liver. The molecular basis is unknown. It can be differentiated from Dubin-Johnson syndrome by:
      BSP excretion Q – clearance of BSP from plasma is delayed in rotor syndrome, but there is no reflux of conjugated BSP back into the circulation as seen in Dubin-Johnson syndrome. There is defect in intra hepato cellular storage of BSP.
      Gall bladder is visualized on oral cholecystography. Q

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