CC2

• Jaundice is a clinical manifestation of liver disease characterized by yellowish discoloration of skin, mucous membrane and sclera of the eyes, and is a visible indication of hyperbilirubinemia.
• Having no exit to the intestine, bile accumulates inside the liver and eventually escapes in the blood causing mixed hyperbilirubinemia.
• Biliary atresia is a condition in which the bile ducts either fail to develop or develop abnormally.
• Jaundice can be classified into three categories: pre-hepatic, hepatic, and post-hepatic.
• Pre-hepatic jaundice, also known as hemolytic/unconjugated hyperbilirubinemia, occurs when the problem causing the jaundice occurs prior to liver metabolism, and is characterized by an increased amount of bilirubin being presented to the liver, such as in acute or chronic hemolytic anemias or failure to convert B1 to B2 due to deficiency of UDPGT.
• Hepatic jaundice occurs when the problem causing the jaundice resides in the liver, and is characterized by disorders of bilirubin metabolism and transport defects or diseases resulting in hepatocellular injury or destruction.
• Post-hepatic jaundice, also known as conjugated/obstructive hyperbilirubinemia, occurs when there is an obstruction in the bile ducts, preventing the flow of conjugated bilirubin into the bile canaliculi.
• Congenital Hyperbilirubinemia can be caused by Gilbert syndrome, a disorder characterized by a transport deficit in the sinusoidal membrane of the hepatocyte due to a mutation of UGT1A1 (insertion of two bases in the promoter region), leading to lower enzymatic activity.
• Gilbert syndrome is often misdiagnosed as chronic hepatitis and may be predisposed to acetaminophen toxicity because acetaminophen is primarily metabolized by glucuronidation.
• The danger of kernicterus is a certainty at levels exceeding 20 mg/dL.
• The distinguishing feature of Dubin - Johnson Syndrome is the intense dark pigmentation of the liver due to accumulation of lipofuschin pigment.
• Increased B1 in Lucey - Driscoll syndrome prevents conjugation.
• Crigler - Najjar Syndrome is a bilirubin conjugation deficit, a more severe and dangerous form of hyperbilirubinemia due to multiple mutations in the UGT1A1 gene.
• In Dubin - Johnson Syndrome, blocked B2 returns to blood and becomes conjugated to albumin forming delta bilirubin.
• Infants with Crigler - Najjar Syndrome are treated by means of phototherapy.
• Type 1 of Crigler - Najjar Syndrome is characterized by complete deficiency of the enzyme UDPGT, manifested by very high concentrations of B1 exceeding 25 mg/dL, and patients die due to severe brain damage within the first year of life.
• Early liver transplantation is the only effective therapy for Type 1 of Crigler - Najjar Syndrome.
• Rotor syndrome is a defective excretion of bilirubin without liver pigmentation, possibly viral induced, and is hypothesized to be due to a reduction in the concentration or activity of intracellular binding proteins such as ligandin.
• Lucey - Driscoll syndrome is caused by a circulating inhibitor to bilirubin conjugation.
• Kernicterus is a severe unconjugated hyperbilirubinemia characterized by deposition of bilirubin in the brain, particularly affecting the basal ganglia, mainly the lenticular nucleus, causing severe motor dysfunction, retardation and possibly death.
• Dubin - Johnson Syndrome is a bilirubin excretion deficit, caused by an inherited deficiency of the canalicular multidrug resistance/multispecific organic anionic transporter/ATP - binding cassette (MRP2/cMOAT/ABCC2) protein inhibiting the release of B2 from the hepatocytes.
• Carotenemia is characterized by the yellowish discoloration of the skin but not the sclera due to increased ingestion of carotenoids.
• Type 2 of Crigler - Najjar Syndrome is characterized by partial deficiency of the enzyme UDPGT, with B1 usually ranging from 5 to 20 mg/dL, and responds to phenobarbital, allowing for a normal life expectancy.
• Acetaminophen is one of the most common drugs associated with serious hepatic injury, and when taken in massive doses, it is certain to produce fatal hepatic necrosis unless rapid treatment is initiated.
• Biliary Obstruction is the most common cause of hyperbilirubinemia in adults, specifically cholelithiasis.
• Other causes of cirrhosis include chronic hepatitis B, D, C infection, autoimmune hepatitis, alpha-1 antitrypsin deficiency, Wilson’s disease, hemochromatosis, galactosemia, and blocked bile duct.
• Drug-induced liver disease accounts for 1/3 to ½ of all reported cases of acute liver failures, with ethanol being the most important drug associated with hepatotoxicity.
• The most common cause of cirrhosis is chronic alcoholism.
• Reye’s syndrome is an acute illness characterized by non-inflammatory encephalopathy and fatty degeneration of the liver, with an increased risk of developing Reye syndrome following the ingestion of aspirin during a viral syndrome.
• Allopurinol is associated with Steven Johnson syndrome.
• Choledocholithiasis is a condition where bile stones are present in the common bile duct.
• Cirrhosis is a clinical condition in which scar tissue replaces normal healthy liver tissue, typically resulting in signs and symptoms such as fatigue, jaundice, nausea, unintended weight loss, bleeding from the GIT, intense itching and swelling of legs and abdomen.