[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Liver and gallbladder](https://durgical.com/en/general-pathology/areas/liver/) › Jaundice and cholestasis # Jaundice and cholestasis - Mechanism Jaundice is yellow skin from bilirubin; it rises when too much is made, the liver cannot process it, or bile cannot drain. Updated Nov 12, 2026 ## Key points - Unconjugated excess: overproduction (hemolysis, ineffective erythropoiesis), less uptake, less conjugation (Gilbert, Crigler-Najjar, neonates). - Conjugated excess: defective canalicular secretion (Dubin-Johnson, Rotor), hepatocellular disease, bile duct obstruction. - Conjugated bilirubin is water-soluble: it appears in urine (dark urine); unconjugated does not. - Unconjugated bilirubin can cross the immature blood-brain barrier: kernicterus in newborns. - Cholestasis: pruritus (bile acids), xanthomas, malabsorption of fat and vitamins A, D, E, K, high alkaline phosphatase and GGT. - Delta bilirubin (bound to albumin) explains why jaundice fades slowly after obstruction is relieved. ## What it is Bilirubin comes mainly from heme of senescent red cells. Unconjugated bilirubin is insoluble, travels on albumin, is taken up by hepatocytes, conjugated by UGT1A1 and secreted into bile. Jaundice appears when the serum level rises enough to stain tissues. Cholestasis is impaired bile flow, with retention of bilirubin, bile acids and cholesterol, and is either hepatocellular or obstructive. Newborns have a physiologic, mostly unconjugated hyperbilirubinemia in the first days of life. ## Key facts - Physiologic jaundice of the newborn: immature UGT1A1, high red cell turnover and enterohepatic recirculation; usually peaks in the first days and resolves within two weeks. - Breast-milk jaundice: a milder, longer unconjugated rise in breastfed infants, linked to factors in milk that favour reabsorption. ## Structure - Cholestasis: bile plugs in dilated canaliculi, brown-green pigment in hepatocytes and Kupffer cells, feathery degeneration of bile-soaked hepatocytes. - Obstruction adds portal edema, ductular reaction and neutrophils, and later bile infarcts. ## Step by step - Macrophages break down heme to biliverdin, then to unconjugated bilirubin. - Unconjugated bilirubin travels in plasma bound to albumin. - Hepatocytes take it up through transporters and conjugate it with glucuronic acid (UGT1A1). - Conjugated bilirubin is pumped into canaliculi by MRP2 and drains with bile into the gut. - Gut bacteria convert it to urobilinogen; part is reabsorbed and excreted in urine, the rest colours stool. - A block at any step raises the bilirubin before it; complete obstruction gives pale stools and dark urine. ## In the lab - Total and direct (conjugated) bilirubin split unconjugated from conjugated causes. - Urine bilirubin is positive only in conjugated hyperbilirubinemia. ## Memory aid Before the liver: too much made; in the liver: badly handled; after the liver: blocked drain. ## Test yourself Think of the answer, then tap the question to see it. ## Why is there no bilirubin in urine in hemolytic jaundice? The excess is unconjugated bilirubin, which is bound to albumin and not water-soluble, so it is not filtered. ## Which enzyme conjugates bilirubin? UDP-glucuronosyltransferase 1A1 (UGT1A1) in the hepatocyte endoplasmic reticulum. ## What causes pruritus in cholestasis? Retained bile acids and other pruritogens in blood and tissues. ## Why do newborns develop physiologic jaundice? Their UGT1A1 activity is immature while red cell turnover and enterohepatic reabsorption of bilirubin are high. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/general-pathology/jaundice-and-cholestasis/) [More Pathology questions →](https://durgical.com/en/practice/?f=pathology) ## Elsewhere in DurgiPedia - [Heme breakdown and bilirubin](https://durgical.com/en/biochemistry/pathways/heme-breakdown-and-bilirubin/) - [Bilirubin](https://durgical.com/en/biochemistry/molecules/bilirubin/) - [UGT1A1 (bilirubin UDP-glucuronosyltransferase)](https://durgical.com/en/biochemistry/enzymes/ugt1a1/) - [Bile and the enterohepatic circulation](https://durgical.com/en/physiology/bile-and-the-enterohepatic-circulation/) ## Connections ## Related 4 - [Hereditary hyperbilirubinemias](https://durgical.com/en/general-pathology/hereditary-hyperbilirubinemias/) - [Large bile duct obstruction](https://durgical.com/en/general-pathology/large-bile-duct-obstruction/) - [Neonatal cholestasis: biliary atresia and neonatal hepatitis](https://durgical.com/en/general-pathology/neonatal-cholestasis-biliary-atresia-and-neonatal-hepatitis/) - [Pigments in tissue: lipofuscin, hemosiderin, melanin, bilirubin, carbon](https://durgical.com/en/general-pathology/pigments-in-tissue-lipofuscin-hemosiderin-melanin-bilirubin-carbon/) ## Related conditions 5 - [Neonatal jaundice](https://durgical.com/en/conditions/neonatal-jaundice/) - [Hereditary spherocytosis](https://durgical.com/en/conditions/hereditary-spherocytosis/) - [Choledocholithiasis](https://durgical.com/en/conditions/choledocholithiasis/) - [Gilbert syndrome](https://durgical.com/en/conditions/gilbert-syndrome/) - [Autoimmune haemolytic anaemia](https://durgical.com/en/conditions/autoimmune-haemolytic-anaemia/) [← All of general pathology](https://durgical.com/en/general-pathology/) Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given. Sources: [Newborn jaundice: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/001559.htm) (MedlinePlus, US National Library of Medicine, 2026); [Cholestasis: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000215.htm) (MedlinePlus, US National Library of Medicine, 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/general-pathology/jaundice-and-cholestasis/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/jaundice-and-cholestasis/