Give an account of the physiological mechanisms underlying various forms of hyperbilirubinaemia, giving appropriate examples.

Outline:

·        Hemolytic:

·        Obstructive:

·        Hepatic:

Essay:

            Hyperbilirubinaemia occurs when the levels of bilirbuin in the blood exceeds 1mg/dL. Excess levels of bilirubin in the bloodstream leads to jaundice, resulting in yellow pigmentation of the skin and sclerae.

            There are three main forms of jaundice hemolytic, obstructive, and hepatic, each with a different underlying physiological mechanism.

            Hemolytic jaundice is due to the production of excessive bilirubin that exceeds the liver’s conjugative capacity. The liver has the capacity to conjugate and excrete over 3000 mg of bilirubin per day. When this limit is exceeded, blood plasma bilirubin becomes elevated. This increased bilirubin production is caused by increased hemolytic lysis of red blood cells, leading to increased degradation of heme. A variety of conditions ranging from enzyme deficiencies (pyruvate kinase, G6PD deficiencies) to hereditary hemoglobinopathies (thalassemias, sickle-cell disease) can precipitate excessive intravascular hemolysis of red blood cells.

            Obstructive jaundice arises from the obstruction of the bile duct. Bile from the liver is unable to reach the gallbladder or duodenum and accumulates, eventually ‘regurgitating’ back into the systemic circulation, elevating the levels of conjugated bilirubin. The presence of a hepatic tumor or bile stones may block the bile ducts, preventing passage of bilirubin into the intestine.

            Hepatic jaundice results directly from damage to the liver cells, decreasing its ability to conjugate bilirubin or impairing the active transport of bilirubin into the bile canaliculi. Bilirubin accumulates in the liver bile canaliculi and is refluxed back into the systemic circulation. This type of jaundice is observed frequently in patients with severe cirrhosis or hepatitis.