Jaundice is a symptom of an underlying pathology and is not a disease. It clinically presents as a yellow discoloration of the skin, eyes and mucous membranes as a consequence of an abnormally increased bilirubin concentration in the blood plasma. Jaundice becomes noticeable first in the eyes, sclera, since bilirubin has a high affinity to a protein called elastin. The sclera is rich with elastin and becomes jaundiced when bilirubin levels increase to 3.0 mg/dL, according to "Harrison's Principles of Internal Medicine 17th Edition".
Bilirubin
Dying or damaged red blood cells or RBCs release hemoglobin which becomes degraded into heme and globin. The heme portion converts into a yellow-green pigment called bilirubin and removed from the body. Diseases that increase RBC destruction, interfere with the uptake or the elimination of bilirubin will result in jaundice. The causes of jaundice are categorized anatomically as prehepatic, intrahepatic, and posthepatic, according to "Pathophysiology 3rd Edition".
Prehepatic Jaundice
Prehepatic or hemolytic jaundice results from an increased rate of RBC hemolysis or destruction. Hemolytic disorders that cause RBC damage can be inherited or acquired. Inherited hemolytic disorders involve mutations or defects in genes producing abnormal hemoglobin, enzymes, and RBC cytoskelatal proteins.
Spectrin is an abundant cytoskelatal protein that maintains the shape and structure of the red blood cell. When a mutated form is inherited, the normal flexible biconcave shape is lost and the cell becomes spherical. This condition is called Hereditary Spherocytosis, according to "Harrison's Principles of Internal Medicine 17th Edition".
A mutation in hemoglobin causes Sickle Cell Disease marked by sickle-shaped RBC's with ridged cell membranes. Sickle cells, like spherocytes, prove unable to pass through the spleen and become removed from circulation.
According to "Harrison's Internal Medicine 17th Edition", mutations in a RBC enzyme called Glucose-6-Phosphate Dehydrogenase or G6PD results in low levels of enzyme activity which increases free radicals inside affected RBC's and damages the cell membrane. Hemolysis gets triggered by infections, ingested fava beans and certain antimalarial medications.
Acquired hemolytic disorders result from blood transfusion reactions, medications, or from an artificial heart valve implant. Since RBC's get destroyed faster than they are produced by the bone marrow, anemia will occur in association with jaundice.
Intrahepatic Jaundice
Intrahepatic or hepatocellular jaundice results when liver cells fail to metabolize and remove bilirubin from circulation. Liver diseases that cause dysfunction of liver cells include viral hepatitis, alcoholic liver disease, and autoimmune hepatitis, according to "Pathophysiology 3rd Edition".
Posthepatic Jaundice
"Harrison's Principles of Internal Medicine 17th Edition" states that posthepatic or obstructive jaundice occurs when the flow of bile from the liver to the small intestine becomes blocked. The bile, containing bilirubin, backs-up into the liver and spills into circulation causing intense itching and jaundice. The most common cause of bile duct obstruction is gallstones. Other causes include carcinoma of the head of the pancreas, common bile duct inflammation, bile duct tumors or tapeworm infection.
References
- "Harrison's Principles of Internal Medicine 17th Edition"; Fauci, et al; 2008
- "Pathophysiology Third Edition"; Copstead, et al; 2005
