Jaundice pathophysiology On the Web
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Bilirubin is the catabolic product of the heme which is the main component of the red blood cells. Bilirubin is formed in the liver and spleen then it passes through several process in order to be metabolized. Metabolism processes include hepatic uptake, conjugation, clearance and excretion of the bilirubin in the bile. Jaundice develops due to increase the level of bilirubin and deposition under the skin and cause the yellow discoloration of the skin. Pathogenesis of neonatal jaundice includes physiologic process of bilirubin accumulation or pathological mechanism. The pathological jaundice may be acquired or inherited. Acquired neonatal jaundice include Rh hemolytic disease, ABO incompatibility disease, and hemolytic disease due to G6PD enzyme deficiency. Inherited neonatal jaundice is due to defect of one of the processes of bilirubin metabolism and it concludes some inherited syndromes. Inherited neonatal jaundice include Gilbert's syndrome, Crigler-Najjar syndrome type I and II, Lucey-Driscoll syndrome, Dubin-Johnson syndrome, and Rotor syndrome.
Bilirubin formation and metabolism
- Bilirubin is the final catabolic product of the heme. The heme is a component of various biological molecules and enzymes but, it is mainly incorporated in the hemoglobin which is the primary component of the red blood cells.
- Bilirubin is formed mainly in the liver and spleen through two steps which include:
- Heme oxygenase enzyme degrades the porphyrin ring of the heme and breaks it down. A green compound called biliverdin is then formed as a result of the previous reaction. Carbon monoxide is released as a result of the reaction.
- Biliverdin reductase enzyme catalyzes the formation of bilirubin from biliverdin.
- Bilirubin is a toxic metabolite so, the body has physiologic processes to eliminate the bilirubin. Bilirubin elimination process includes:
- Hepatic uptake
- Clearance and excretion
- After conjugation of the bilirubin in the liver, it is secreted into the bile then into the gastrointestinal tract.
- In the GIT, the conjugated bilirubin is metabolized by the gut enzymes into urobilinogen which is oxidized into urobilin.
- Metabolism of the conjugated bilirubin occurs properly in the adults. However, the newborns have sterile gastrointestinal canal which impedes the catalyzation of the conjugated bilirubin.
- The sterile tract ends up with a small amount of excreted bile.
- The remaining conjugated bilirubin is unconjugated by the beta-glucuronidase enzyme in the neonatal intestine.
- The unconjugated bilirubin is reabsorbed back into the blood and to the liver through the enterohepatic circulation of bilirubin.
- A small amount of bilirubin is cleared into the urine as urobilinogen.
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Pathogenesis of Adult jaundice
- Jaundice in adult patients classified into two major types:
- Overproduction of bilirubin
- Reduced bilirubin uptake
- Impaired bilirubin conjugation
- The combination of progestational and estrogenic steroids may result in increased UDP-glucuronyl transferase activity
Biliary tract obstruction
- Biliary tract obstruction leads to both conjugated and unconjugated bilirubinemia.
- Bilirubin is transported back to the plasma by ATP-consuming pumps.
- The markers are serum concentrations of bilirubin and alkaline phosphatase.
- Biliary retention secondary to obstruction may reverse the glucuronidation.
- Produced unconjugated bilirubin will diffuse or be transported back into the plasma.
- Mirizzi syndrome
- Primary sclerosing cholangitis and cholangiocarcinoma
- AIDS cholangiopathy
- Cryptosporidium species
- Viral hepatitis (hepatitis viruses, herpes simplex virus, Epstein-Barr virus)
- Mycobacterium tuberculosis and atypical mycobacteria (especially Mycobacterium avium intracellulare)
- Fungal infections (Cryptococcus neoformans, Histoplasma capsulatum, Candida albicans, Coccidioides immitis)
- Parasites (Pneumocystis carinii)
- Tumor infiltration (lymphoma, Kaposi sarcoma)
- Drug-induced liver disease
Liver infrastructure damage
- Viral hepatitis: For more information about viral hepatitis click here
- Alcoholic hepatitis: For more information about viral hepatitis click here
- Nonalcoholic steatohepatitis: For more information about viral hepatitis click here
- Primary biliary cholangitis: For more information about viral hepatitis click here
- Sepsis and low perfusion states
- Paraneoplastic syndromes
- Infiltrative diseases of the liver
- Total parenteral nutrition (TPN)
- At least two to three weeks of TPN may lead to development of cholestasis.
- Intestinal endotoxins transfer into the portal system
- Bacterial sepsis
- Formation of secondary bile acids (e.g., lithocholic acid)
- Biliary sludge after six weeks of TPN
- Hepatotoxic factors, such as tryptophan degradation metabolites and aluminum contaminants
- Bacterial overgrowth in the small intestine
- At least two to three weeks of TPN may lead to development of cholestasis.
- Sickle cell disease
- Intrahepatic cholestasis of pregnancy
- Different presentations simulate cholestatic syndromes.
- Intracellular proteins and small molecules are released into the plasma.
- Increased transaminases, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT).
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