上海交通大学：《诊断学》课程PPT教学课件（英语版）Chapter 16 Jaundice

J aundice Definition Accumulation of yellow pigment in the skin and other tissues bilirubin)

Jaundice Definition Accumulation of yellow pigment in the skin and other tissues (Bilirubin)

Bilirubin metabolism a Bilirubin formation Transport of bilirubin in plasma Hepatic bilirubin transport s Hepatic uptake * Conjugation 冷 Biliary excretion Enterohepatic circulation

Bilirubin Metabolism ◼ Bilirubin formation ◼ Transport of bilirubin in plasma ◼ Hepatic bilirubin transport ❖ Hepatic uptake ❖ Conjugation ❖ Biliary excretion ◼ Enterohepatic circulation

Bilirubin formation 120ds RBCs-Senecent RBCs Iron hemoglo bin Globin Chiefly 70+% Bilirubin R Biliverdin CBR o heme Bilir 20% rubin nonhemoglobin heme Hepatic Hemoproteins nonhemoglobin hemoprotein 1-5% Premature destruction of newly formed rBCs

Bilirubin RBCs Senecent RBCs Iron hemoglobin Globin Bilirubin Biliverdin heme Hepatic Hemoproteins nonhemoglobin heme nonhemoglobin hemoprotein Premature destruction of newly formed RBCs C MHO R CBR 1-5% Chiefly 70+% 20% Bilirubin formation 120ds

Transport of Bilirubin in Plasma Albumin + UB+ UB- Albumin complex h afiinity binding sites 2:1/ Bilirubin Molar Plasma protein Ratio Albumin L affinity binding sites >2: 1 Bilirubin Other organic anions can be replaced b PHA UB↑

Transport of Bilirubin in Plasma Albumin + UB UB ~ Albumin Complex Molar Ratio Bilirubin Bilirubin Plasma protein Albumin H affinity binding sites L affinity binding sites can be replaced by Other organic anions PH UB 2:1 >2:1

Hepatic Bilirubin Transport 1. Hepatic uptake of Bilirubin UCB-Albumin Complex separated (be) taken up Bilirubin MTA(receptor Plasma membrane of the liver 2. Conjugation of Bilirubin ligation (Y protein) carrier transfer UCB (be) bound to ER (lipid soluble) protein Conjugation Z protein (catalized by UDPGT 3. Biliary Excretion of Bilirubin CB CBGA (water soluble) Transfer across CB → Bile canaliculus Microvillar membrane

CB 1. Hepatic uptake of Bilirubin UCB~Albumin Complex Separated Bilirubin Plasma membrane of the liver (be) taken up MTA (receptor ?) Transfer across Microvillar membrane 3.Biliary Excretion of Bilirubin Bile canaliculus 2.Conjugation of Bilirubin UCB carrier protein ER CB CBGA (be) bound to transfer Conjugation (catalized by UDPGT) ligation (Y protein) Hepatic Bilirubin Transport (lipid soluble) (water soluble)

UDPGT: Uridine Diphosphate glucuronyl Transferase UCB: because of its tight albumin binding and lipid solubility, it is not excreted in urine。 CB: is less tightly bound to albumin and is water soluble. so it is filtered at the glomerulus and appears in the urine

• UDPGT: Uridine Diphosphate Glucuronyl Transferase • UCB: because of its tight albumin binding and lipid solubility, it is not excreted in urine. • CB: is less tightly bound to albumin and is water soluble, so it is filtered at the glomerulus and appears in the urine

Entero-hepatic circulation cB-TBandi be degraded Urobilinogen(coloreds) Bacterial Enzymes feces(fecal urobilinogen) 50-200mgd most re-excreted excreted 90%,liver Bile → feces 20% Reabsorbed→→ plasma trace circulation--kidneys 4 mg/d urine urobilinogen . The serum of normal adults contains sI mg of bilirubin per 100 ml .In healthy adults The direct fraction is usually <0.2 mg/100 ml The indirect fraction is usually <0.8 mg/100 ml

Entero-hepatic circulation CB B and I Urobilinogens (coloress) be degraded Bacterial Enzymes feces (feceal urobilinogens) Reabsorbed plasma circulation kidneys 50-200 mg/d mostly 4 mg/d urine urobilinogen T liver Bile feces re-excreted excreted 90% trace 20% •The serum of normal adults contains 1 mg of bilirubin per 100 ml. •In healthy adults The direct fraction is usually <0.2 mg/100 ml The indirect fraction is usually <0.8 mg/100 ml

Pathophysiologic classification of Jaundice a Hemolytic Jaundice a Hepatic Jaundice a Obstructive jaundice

Pathophysiologic classification of Jaundice ◼ Hemolytic Jaundice ◼ Hepatic Jaundice ◼ Obstructive Jaundice

Hemolytic Jaundice Pathogenesis Overproduction s Hemolysis(intra and extra vascular) inherited or genetic disorders x acquired immune hemolytic anemia (Autoimmune hemolytic anemia) x nonimmune hemolytic anemia (paroxysmal nocturna Hemoglobinruia) .s Ineffective erythropoiesis Overproduction may overload the liver with UB

Hemolytic Jaundice Pathogenesis Overproduction ❖ Hemolysis (intra and extra vascular)  inherited or genetic disorders  acquired immune hemolytic anemia (Autoimmune hemolytic anemia)  nonimmune hemolytic anemia (paroxysmal nocturna Hemoglobinruia) ❖ Ineffective erythropoiesis Overproduction may overload the liver with UB