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Definition
Accumulation of yellow pigment in the skin and other tissues (Bilirubin)
Bilirubin Metabolism
Bilirubin formation
Hepatic uptake
Conjugation Biliary excretion
Enterohepatic circulation
Bilirubin formation
RBCs
Chiefly 70+%
120ds
Senecent RBCs
Bilirubin
1-5%
Bilirubin
L affinity binding sites
Molar Ratio
>2:1
Bilirubin
Other organic anions can be replaced by PH
UB
2.Conjugation of Bilirubin
ligation (Y protein)
(be) bound to
UCB
(lipid soluble)
carrier protein
transfer
ER
Conjugation (catalized by UDPGT)
CB
CBGA
(water soluble)
Bile canaliculus
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 T B and I be degraded Bacterial Enzymes Urobilinogens (coloress)
mostly
20%
Reabsorbed
plasma
trace
circulation
4 mg/d
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
Jaundice classification
predominantly unconjugated hyperbilirubinaemia predominantly conjugated hyperbilirubinaemia
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
Hemolytic Jaundice
Symptoms
weakness, Dark urine, anemia, Icterus, splenomegaly
Lab
UB without bilirubinuria fecal and urine urobilinogen hemolytic anemia hemoglobinuria (in acute intravascular hemolysis) Reticulocyte counts
Hemolytic Jaundice
(pre-hepatic)
Serum / blood: bilirubin (micormoles/l) 50-150; normal range 3-17 AST I.U. < 35; normal range <35 ALP I.U. <250; normal range <250 gamma GT I.U. 15-40; normal range 15-40 albumin g/l 40-50; normal range 40-50 reticulocytes(%) 10-30; normal range <1 prothrombin time (seconds) 13-15; normal range 13-15
Hemolytic Jaundice
(pre-hepatic) urinary changes: bilirubin: absent urobilinogen: increased or normal faecal changes: stercobilinogen: normal
Obstructive Jaundice
Pathogenesis
it is due to intra- and extra hepatic obstruction of bile ducts intrahepatic Jaundice: Hepatitis, PBC, Drugs Extra Hepatic Biliary Obstruction: Stones, Stricture, Inflammation, Tumors, (Ampulla of Vater)
Obstructive Jaundice
extrahepatic
serum / blood bilirubin (micromoles/l) 100-500; normal range 3-17 AST I.U. 35-400; normal range <35 ALP I.U. >500; normal range <250 gamma GT I.U. 30-50; normal range 15-40 albumin g/l 30-50; normal range 40-50 reticulocytes(%) <1; normal range <1 prothrombin time (secs) 15-45; normal range 13-15 ( " + parenteral vitamin K) falls
Obstructive Jaundice
extrahepatic
urinary changes bilirubin: increased urobilinogen: reduced or absent faecal changes stercobilinogen: reduced or absent
Hepatic Jaundice
Due to a disease affective hepatic tissue either congenital or acquired diffuse hepatocellular injury
Hepatic Jaundice
Pathogenesis
Impaired or absent hepatic conjugation of bilirubin
decreased GT activity (Gilberts syndrome) hereditary absence or deficiency of UDPGT (Grigler-Najjar Syndrome)
Dubin-Johnson Syndrome Rotor syndrome hepatocellular necrosis intrahepatic cholestasis
(Hepatitis, Cirrhosis, Drug-related)
Acquired disorders
Hepatic Jaundice
Symptoms
weakness, loss appetite, hepatomegaly, palmar erythema, spider
Lab Findings
liver function tests are abnormal
Hepatic Jaundice
serum / blood bilirubin (micromoles/l) 50-250; normal range 3-17 AST I.U. 300-3000; normal range <35 ALP I.U. <250-700; normal range <250 gamma GT I.U. 15-200; normal range 15-40 albumin g/l 20-50; normal range 40-50 reticulocytes(%) <1; normal range <1 prothrombin time (secs) 15-45; normal range 13-15 ( " + parenteral vit. K) 15-45
Hepatic Jaundice
urinary changes bilirubin: normal or increased urobilinogen: normal or reduced faecal changes stercobilinogen: normal or reduced
Jaundice diagnosis(1)
history and examination urine, stools serum biochemistry bilirubin transaminases - AST, ALT albumin alkaline phosphatase
Jaundice diagnosis(2)
haematology haemoglobin WCC platelets prothrombin time +/- parenteral vitamin K abdominal ultrasound and chest X-ray further investigations - determined by the basis of the jaundice, e.g. prehepatic, hepatic, extra-hepatic
conjugated hyperbilirubinaemia
the liver is able to conjugate bilirubin, but the excretion is impaired. failure of bilirubin excretion by hepatocytes: Dubin-Johnson syndrome Rotor's syndrome obstruction to biliary flow i.e. cholestasis, both intra-hepatic and extra-hepatic
unconjugated hyperbilirubinaemia
increased bilirubin formation failure of bilirubin uptake(Gilbert's disease) failure of bilirubin conjugation
unconjugated
hyperbilirubinaemia
increased bilirubin formation
unconjugated hyperbilirubinaemia
failure of bilirubin conjugation
neonatal jaundice Crigler Najjar syndrome drug inhibition e.g. chloramphenicol extensive hepatocellular disease e.g. hepatitis, cirrhosis
Cholestasis diagnosis
elevated serum bilirubin - in proportion to duration of cholestasis; returns to normal once cholestasis is relieved raised serum alkaline phosphatase - to more than 3X upper limit of normal; LFTs - aminotransferases mildly raised; raised gamma GT increased urinary bilirubin urinary urinobilinogen is excreted in proportion to amount of bile reaching the duodenum i.e. absence of urinobilinogen indicates complete biliary obstruction
Identification of cause
dilated ducts on ultrasound percutaneous transhepatic cholangiograpy undilated ducts on ultrasound endoscopic retrograde cholangiopancreatography needle biopsy of the liver
Hepatocellular carcinoma
Accompanied Symptoms
Fever Pain,Charcot syndrome Hepatomegaly Spleenmegaly Ascites GI bleeding itch
UCB or CB Exclude UCB (e.g. hemolysis or Gilbert Synd.) Distinguish hepatocellular from obstructive Distinguish intrahepatic from extra hepatic cholestasis
Case Study1
History: 68-year-old,jaundice,stomach pain, dark urine,itching of the skin,rapid weight loss of 21lb Lab data CBC within narmal limits Total bilirubin:238mol/l GGT:300U/l ALP:360U/l AST:80u/l ALT:75u/l Urinalysis:positive bilirubin,normal urobilinogen Serum amylase:elevated
Case Study1
Question:
What is the most probable diagnosis for this patient? Which labtory tests provided the most information,and which provided the least?
Case Study2
History:38-year-old white female,jaundice,right upper quadrant abdominal pain,nausea,vomiting,itching skin.She has a history of intravenous drug use and alcohol abuse.
Case Study2
Lab data elevated total bilirubin(136 mol/l) elevated conjugated bilirubin(102mol/l) Urine:orange-brown,3+bilirubin,normal urobilinogen elevated ALP(1.5ULT),GGT(3ULT),ALT,AST(5ULT) Modest increase:Serum cholesterol and triglyceride
Case Study2
Question
What is the probable diagnosis for this patient?Why? What other laboratory test would recommend to confirm this diagnosis? Which laboratory tests ordered provided the most information?Why?
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