case of obstructive jaundice.ppt
DESCRIPTION
obstructive jaundiceTRANSCRIPT
Jaundice
Definition
Accumulation of yellow pigment in
the skin and other tissues (Bilirubin)
Bilirubin Metabolism Bilirubin formation
Transport of bilirubin in plasma
Hepatic bilirubin transport Hepatic uptake
Conjugation
Biliary excretion
Enterohepatic circulation
Bilirubin
RBCs Senecent RBCsIronhemoglobinGlobin
Bilirubin Biliverdin heme
Hepatic Hemoproteins nonhemoglobin hemenonhemoglobin hemoprotein
Premature destruction of newly formed RBCs
CMHO
RCBR
1-5%
Chiefly70+%
20%
Bilirubin formation
120ds
Transport of Bilirubin in Plasma
Albumin + UB UB ~ Albumin Complex
MolarRatio
Bilirubin
Bilirubin
Plasma proteinAlbumin
H affinity binding sites
L affinity binding sites
can be replaced byOther organic anions
PH UB
2:1
>2:1
CB
1. Hepatic uptake of BilirubinUCB~Albumin Complex Separated
Bilirubin Plasma membrane of the liver(be) taken upMTA (receptor ?)
Transfer across
Microvillar membrane
3.Biliary Excretion of Bilirubin
Bile canaliculus
2.Conjugation of Bilirubin
UCB carrier protein ER
CBGACB
(be) bound to transfer
Conjugation(catalized by UDPGT)
Z protein
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.
Entero-hepatic circulation
CB B and I Urobilinogens (coloress) be degradedBacterial Enzymes
feces (feceal urobilinogens)
Reabsorbed plasma
circulation kidneys
50-200 mg/dmostly
urine urobilinogen4 mg/d
T
liver Bile fecesre-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 mlThe indirect fraction is usually <0.8 mg/100 ml
Pathophysiologic classification of Jaundice
Hemolytic Jaundice
Hepatic Jaundice
Obstructive Jaundice(Cholestasis)
Congenital Jaundice
Jaundice classification
predominantly unconjugated hyperbilirubinaemia
predominantly conjugated hyperbilirubinaemia
Hemolytic Jaundice Pathogenesis
OverproductionHemolysis (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
Hemolytic JaundiceSymptoms 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
normalfaecal changes: stercobilinogen: normal
Obstructive Jaundice
Pathogenesisit 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)
Etiology of Obstructive Jaundice
Intrahepatic-Liver cell Damage/Blockage of Bile Canaliculi
• Drugs or chemical toxins• Dubin-Johnson syndrome• Estrogens or Pregnancy• Hepatitis-viral,chemical• Infiltrative tumors• Intrahepatic biliary hypoplasia or atresia• Primary biliary cirrhosis
Etiology of Obstructive Jaundice
Extrahepatic-Obstructive of bile Ducts
• Compression obstruction from tumors
• Congenital choledochal cyst
• Extrahepatic biliary atresia
• Intraluminal gallstones
• Stenosis-postoperative or inflammary
cholestasisclinical features
• pain, due to gallbladder disease, malignancy, or stretching of the liver capsule
• fever, due to ascending cholangitis
• palpable and / or tender gallbladder
• enlarged liver, usually smooth
General signs of cholestasis
• xanthomas: palmar creases, below the breast, on the neck. They indicate raised serum cholesterol of several months. Xanthomas on the tendon sheaths are uncommonly associated with cholestasis.
• xanthelasma on the eyelids • scratch marks: excoriation • finger clubbing • loose, pale, bulky, offensive stools • dark orange urine
Obstructive Jaundice Lab Findings• Serum Bilirubin• Feceal urobilinogen (incomplete obstruction)• Feceal urobilinogen absence (complete
obstruction)• urobilinogenuria is absent in complete
obstructive jaundice• bilirubinuria • ALP • cholesterol
Obstructive Jaundiceextrahepatic
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 (Gilbert‘s syndrome) hereditary absence or deficiency of UDPGT (Grigler-Najjar
Syndrome)
• Familiar or hereditary disorders Dubin-Johnson Syndrome Rotor syndrome
• Acquired disorders hepatocellular necrosis intrahepatic cholestasis
(Hepatitis, Cirrhosis, Drug-related)
Hepatic Jaundice
Symptoms
weakness, loss appetite, hepatomegaly, palmar
erythema, spider
Lab Findings
• liver function tests are abnormal
• both CB and UCB
• Bilirubinuria
Hepatic Jaundiceserum / 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
Jaundicediagnosis(1)
history and examinationurine, stoolsserum biochemistry • bilirubin • transaminases - AST, ALT • albumin • alkaline phosphatase
Jaundicediagnosis(2)
haematology• haemoglobin • WCC • platelets • prothrombin time +/- parenteral
vitamin Kabdominal ultrasound and chest X-rayfurther investigations - determined by
the basis of the jaundice, e.g. pre-hepatic, 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 syndromeobstruction to biliary flow i.e. cholestasis,
both intra-hepatic and extra-hepatic
The proportion of conjugated bilirubin to the total raised
bilirubin
• 20-40% of total: more suggestive of hepatic than posthepatic jaundice
• 40-60% of total: occurs in either hepatic or posthepatic causes
• > 50% of total: more suggestive of posthepatic than hepatic jaundice
• less than 20% :secondary to haemolysis or constitutional e.g. Gilbert's disease, Crigler-Najjar syndrome
unconjugated hyperbilirubinaemia
• increased bilirubin formation• failure of bilirubin
uptake(Gilbert's disease)• failure of bilirubin
conjugation
unconjugated
hyperbilirubinaemia increased bilirubin formation
haemolysis ineffective erythropoiesis: • megaloblastic anaemia • iron deficiency • haemoglobinopathies
unconjugated hyperbilirubinaemia
failure of bilirubin conjugation
• neonatal jaundice • Crigler Najjar syndrome • drug inhibition e.g.
chloramphenicol • extensive hepatocellular
disease e.g. hepatitis, cirrhosis
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 limitsTotal bilirubin:238μmol/lGGT:300U/lALP:360U/lAST:80u/lALT:75u/lUrinalysis:positive bilirubin,normal urobilinogenSerum 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 μmol/l) elevated conjugated bilirubin(102μmol/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?