cholestasis- mohamed mohi

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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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