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Cholestasis
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OATP:
Organic Anion Transporting Protein.
UCB:
Unconjugated bilirubin.
L: Ligand
BDG:
Di-glucuronidated bilirubin.
BMG:
Mono-glucuronidated bilirubin.
UGT:
UDP- glucuronyl transferase.
MRP2:
Multi-drug resistance associated
protein.
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Definitions:
J aundice:
yellowish discoloration of the skin and
mucus memberanes.
Cholestasis:
Interruption of bile flow or formation
anywhere between the basolateral(sinusoidal) membrane of the hepatocyte
and the ampulla of Vater.
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Classification
Intrahepatic or extrahepatic.
Mechanical or functional (decreased
hepatic secretion of H2O and/or
organic anions; bil.and bile acids).
Acute or chronic.
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Surgical cholestasis:
Outside :•Choledochal cyst.
•Diverticulum.
•Pancreatic tumour.
•Pancreatitis.
•LNs or Hepatoma
Inside the lumen: •Stone.
•Blood (haemobilia)
•Parasites
• Ascaris•Hydatid
•Fasciola
•Papillary stenosis.Wall:
•Congenital atresia.
•Stricture.
•Sclerosing cholangitis.
•Cholangiocarcinoma.
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Choledochal cyst:
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Medicalcholestasis
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TB
Sarcoidosis
Amyloidosis (late)
Hodgiken’s lymphoma Malignancy
- A Infiltrative disease
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B- Diseases involving bile ductules
PBC Up regulation of HLA
class I
→ infiltration of the bile duct
with CTL & ↓↓ STL .
↑↑ Cytokines →
liver cell damage.
PSC Unknown.
?? familial incidence,
?? genetic factors
?? autoimmune processes,
(subliminal
portogenous bacterial or
endotoxin damage)
Graft versus host disease
Drug induced hepatotoxicity
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Primary sclerosing cholangitis
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Last trimester.
Jaundice is rarely deep.
& disappears after delivery.Within 1-2 weeks the pruritis ceases.
The condition is usually recurrent.
Excellent prognosis for the mother.
↑↑ risk of fetal distress, prematurity anddeath.
Multifactorial.
C-Cholesasis with pregnancy
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D-Cholestasis with minimal
histologic changes
• Benign recurrant cholestasis:
•Rare,
•autosomal recessive benign disorder
•Recurrent attacks of pruritis & jaundice.
•May begin at childhood or adulthood•Misdiagnosed as acute viral hepatitis.
•Several weeks to months.
•Intervals : several months to years
• Attack : malaise,
•↑ ALP, AST, ALT and bilirubin
•In between•free clinical & biochemical.
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• Progressive familial intrahepatic cholestasis
•
Three phenotypically related syndromes• intrahepatic cholestasis, fibrosis, cirrhosis and liver failure.
• Liver transplantation is the treatment.
Type I Type 2 Type 3
Mutation PFIC1 BSEP MDR3
GGT N or slightly N or slightly
Symptoms Early Later than
1&2
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Alagille’s syndrome(Syndromic paucity of intra-hepatic bile ducts) :
• Autosomal dominant
•Due to mutation in one of transmembrane
receptor proteins called the Jagged 1 gene.
•It presents in infancy or early childhood.
•The face is triangular with prominent broad forehead,
deep seated eyes,
a flattened nose and
prominent mandible.
•There is usually HSM and
peripheral pulmonary arterial stenosis.
•The patient survives into adult life
with varying degrees of growth and mental retardation.Liver transplantation is questionable.
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E) Familial defects in hepatic excretion
Item 1) Dubin Johnson 2) Rotor
Incidence Rare Very rare
Colour of liver Dark (pigmentation) Normal
GB on oral
cholecystographyNon-visualized Visualize
d
Urinary coproporhyrin
Amount
Pattern
Normal
>80% type I
Increase
d
70%
type I
BSP excretion Reflux of conj. BSP back into
circulationNo reflux
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Xanthomas
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