5.24
Jaundice, or icterus, develops when plasma bilirubin levels are approximately 2.5 to 3 milligrams per deciliter, leading to yellow discoloration of the skin, sclerae, and mucous membranes.
Bilirubin is produced and eliminated through a normal physiological process that begins with the breakdown of red blood cells.
Macrophages degrade hemoglobin into globin and heme.
Globin is converted into amino acids for reuse, while heme is turned into biliverdin by heme oxygenase. Biliverdin reductase then reduces biliverdin to lipid-soluble unconjugated bilirubin.
Unconjugated bilirubin binds to albumin for transport in the bloodstream to the liver.
In hepatocytes, the enzyme uridine diphosphate-glucuronosyl transferase conjugates bilirubin with glucuronic acid, forming water-soluble conjugated bilirubin.
The liver then secretes this conjugated bilirubin into bile, which is excreted into the intestine.
Disruption at any stage of bilirubin metabolism, whether due to increased production, impaired hepatic uptake or conjugation, or obstruction of bile excretion, can lead to elevated serum bilirubin levels.
Jaundice, or icterus, is the yellow discoloration of the skin, sclerae, and mucous membranes. It happens when plasma bilirubin levels rise above 2.5-3 mg/dL, leading to bilirubin deposition in tissue.
Bilirubin is a byproduct of hemoglobin degradation. In macrophages, hemoglobin breaks down into globin and heme. Globin is converted into amino acids, while heme is turned into biliverdin by heme oxygenase, which is then reduced to unconjugated bilirubin by biliverdin reductase.
Unconjugated bilirubin, being lipid-soluble, circulates in the bloodstream bound to albumin. Hepatocytes in the liver absorb it and conjugate it with glucuronic acid through the enzyme uridine diphosphate-glucuronosyltransferase (UGT1A1). The resulting conjugated bilirubin is water-soluble and released into bile, which is excreted into the intestine.
Jaundice happens when any part of this metabolic pathway is disrupted, leading to bilirubin accumulation in the blood. The underlying mechanisms are classified into prehepatic, intrahepatic, and posthepatic jaundice.
Prehepatic jaundice results from excessive red blood cell destruction, leading to elevated unconjugated bilirubin levels. The liver can't conjugate it quickly enough, resulting in blood accumulation. Since unconjugated bilirubin isn't water-soluble, it doesn't appear in urine.
Examples: sickle cell anemia, hemolytic anemias, malaria, and transfusion reactions.
Findings: Elevated unconjugated bilirubin, normal liver enzymes, no bilirubinuria.
Hepatocyte dysfunction or intrahepatic obstruction impairs bilirubin processing, leading to elevated levels of both unconjugated and conjugated bilirubin.
Examples: Viral hepatitis, drug-induced liver injury, Gilbert syndrome.
Findings: Mixed hyperbilirubinemia, elevated ALT/AST, and possible bilirubinuria.
Posthepatic jaundice happens when obstruction in the extrahepatic bile ducts prevents conjugated bilirubin from reaching the intestine. This results in bilirubin entering the bloodstream, causing dark urine, while reduced bile flow leads to pale stools and fat malabsorption.
Examples: Gallstones, pancreatic cancer, cholangiocarcinoma.
Findings: Elevated conjugated bilirubin, high alkaline phosphatase, dark urine, pale stools, and pruritus.
Jaundice, or icterus, develops when plasma bilirubin levels are approximately 2.5 to 3 milligrams per deciliter, leading to yellow discoloration of the skin, sclerae, and mucous membranes.
Bilirubin is produced and eliminated through a normal physiological process that begins with the breakdown of red blood cells.
Macrophages degrade hemoglobin into globin and heme.
Globin is converted into amino acids for reuse, while heme is turned into biliverdin by heme oxygenase. Biliverdin reductase then reduces biliverdin to lipid-soluble unconjugated bilirubin.
Unconjugated bilirubin binds to albumin for transport in the bloodstream to the liver.
In hepatocytes, the enzyme uridine diphosphate-glucuronosyl transferase conjugates bilirubin with glucuronic acid, forming water-soluble conjugated bilirubin.
The liver then secretes this conjugated bilirubin into bile, which is excreted into the intestine.
Disruption at any stage of bilirubin metabolism, whether due to increased production, impaired hepatic uptake or conjugation, or obstruction of bile excretion, can lead to elevated serum bilirubin levels.
From Chapter 5:
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