thumbJaundice is typically caused by an underlying pathological process that occurs at some point along the normal physiological pathway of heme metabolism. A deeper understanding of the anatomical flow of normal heme metabolism is essential to appreciate the importance of prehepatic,<unk> , and posthepatic categories. Thus, an anatomical approach to heme metabolism precedes a discussion of the pathophysiology of jaundice. Normal heme metabolism Prehepatic metabolism When red blood cells complete their lifespan of about 120 days, or if they are damaged, they rupture as they pass through the reticuloendothelial system, and cell contents including hemoglobin are released into circulation. Macrophages phagocytose free hemoglobin and split it into heme and globin. Two reactions then take place with the heme molecule. The first oxidation reaction is catalyzed by the microsomal enzyme heme oxygenase and results in biliverdin (green color pigment), iron, and carbon monoxide. The next step is the reduction of biliverdin to a yellow color tetrapyrrole pigment called bilirubin by cytosolic enzyme biliverdin reductase. This bilirubin is "unconjugated", "free", or "indirect" bilirubin. Around 4 mg of bilirubin per kg of blood are produced each day. The majority of this bilirubin comes from the breakdown of heme from expired red blood cells in the process just described. Roughly 20% comes from other heme sources, however, including ineffective erythropoiesis, and the breakdown of other heme-containing proteins, such as muscle myoglobin and cytochromes. The unconjugated bilirubin then travels to the liver through the bloodstream. Because this bilirubin is not soluble, it is transported through the blood bound to serum albumin.<unk>  metabolism Once unconjugated bilirubin arrives in the liver, liver enzyme UDP-glucuronyl transferase conjugates bilirubin + glucuronic acid → bilirubin diglucuronide (conjugated bilirubin). Bilirubin that has been conjugated by the liver is water-soluble and excreted into the gallbladder. Posthepatic metabolism Bilirubin enters the intestinal tract via bile. In the intestinal tract, bilirubin is converted into urobilinogen by symbiotic intestinal bacteria. Most urobilinogen is converted into stercobilinogen and further oxidized into stercobilin. Stercobilin is excreted via feces, giving stool its characteristic brown coloration. A small portion of urobilinogen is reabsorbed back into the gastrointestinal cells. Most reabsorbed urobilinogen undergoes hepatobiliary recirculation. A smaller portion of reabsorbed urobilinogen is filtered into the kidneys. In the urine, urobilinogen is converted to urobilin, which gives urine its characteristic yellow color. Abnormalities in heme metabolism and excretion One way to understand jaundice pathophysiology is to organize it into disorders that cause increased bilirubin production (abnormal heme metabolism) or decreased bilirubin excretion (abnormal heme excretion). Prehepatic pathophysiology Prehepatic jaundice is attributed to a pathological increase in bilirubin production. The pathophysiology is quite simple; an increased rate of erythrocyte hemolysis → increased bilirubin production → increased deposition of bilirubin in mucosal tissue → appearance of yellow hue.<unk>  pathophysiology<unk>  jaundice <unk> ellular jaundice) is due to significant damage to liver function →<unk>  cell death and necrosis occur → impaired bilirubin transport across<unk> ytes. Bilirubin transport across<unk> ytes may be impaired at any point between<unk> ellular uptake of unconjugated bilirubin and<unk> ellular transport of conjugated bilirubin into the gallbladder. In addition, subsequent cellular edema due to inflammation causes mechanical obstruction of intrahepatic biliary tract. Most commonly, interferences in all three major steps of bilirubin metabolism — uptake, conjugation, and excretion — usually occur in<unk> ellular jaundice. Thus, an abnormal rise in both unconjugated and conjugated bilirubin will be present. Because excretion (the rate-limiting step) is usually impaired to the greatest extent, conjugated hyperbilirubinemia predominates. The unconjugated bilirubin still enters the liver cells and becomes conjugated in the usual way. This conjugated bilirubin is then returned to the blood, probably by rupture of the congested bile canaliculi and direct emptying of the bile into the lymph leaving the liver. Thus, most of the bilirubin in the plasma becomes the conjugated type rather than the unconjugated type, and this conjugated bilirubin, which did not go to intestine to become urobilinogen, gives the urine the dark color. Posthepatic pathophysiology Posthepatic jaundice (obstructive jaundice) is due to a blockage of bile excretion from the biliary tract → increased conjugated bilirubin and bile salts. In complete obstruction of the bile duct, conjugated bilirubin cannot access the intestinal tract → no further bilirubin conversion to urobilinogen → no stercobilin or urobilin. Instead, excess conjugated bilirubin is filtered into the urine without urobilinogen in obstructive jaundice. Conjugated bilirubin in urine (bilirubinuria) gives urine an abnormally dark brown color. Thus, the presence of pale stool (stercobilin absent from feces) and dark urine (conjugated bilirubin present in urine) suggest an obstructive cause of jaundice. Because these associated signs are also positive in many<unk>  jaundice conditions, they cannot be a reliable clinical feature to distinguish obstruction versus<unk> ellular jaundice causes.
symptom of Hepatic veno-occlusive disease
symptom of Autoimmune hepatitis
symptom of Liver cancer
symptom of Primary biliary cholangitis
symptom of Portal hypertension
symptom of Ascariasis
symptom of Hepatitis B
symptoms of Primary biliary cholangitis