Cholestasis

Micrograph showing cholestasis, as is apparent by the yellow bile. H&E stain. (WC)

In liver pathology, cholestasis is a stoppage or abnormally slow flow of bile.

Cholestatic hepatitis and feathery degeneration redirect to this article.

General

Clinical - classic:

• Dark urine and light stools.

Short DDx - by etiology

• Congenital: Bile duct cyst, biliary atresia, liver cysts.
• Infectious: Worm.
• Tumour: pancreas, bile duct, liver.
• Endocrine: cholestasis of pregnancy.
• Trauma -> sepsis.
• Autoimmune: PSC, PBC.
• Toxins: alcohol -> cirrhosis.
• Everything else: drugs, e.g. NSAIDs.

Short DDx - structural

• Obstruction - large duct:
  • Tumour.
  • Gallstone.
  • Worm.
  • PSC.
• Small duct - autoimmune:
  • PBC.
• Other:
  • Rx.
  • Toxins.
  • Cholestasis of pregnancy.

Microscopic

Appearance of bile:

• Smooth/homogenous.
• Brown/yellow.
• Globule/droplet - that is larger than an iron granule.

Note:

• Iron in bile ducts or endothelial cell = non-specific, used to be thought to be specific for hereditary hemochromatosis.

Brown/yellow cytoplasmic inclusions

Comparison of brown/yellow cytoplasmic inclusions:

Finding	Colour	Granularity	Refractile	Usual location	Association	Stain	Image
Iron	Brown	Coarse granules	Yes - shinny	Periportal (zone I)	Hemolysis, hereditary hemochromatosis	Prussian blue +ve	Iron and bile. (WC)
Bile	Brown - coffee stained	Not granular	No - dull	Portal	Duct injury/obstruction	None	Bile. (WC)
Lipofuscin	Yellow	Fine granules	No	Centrilobular (zone III)	Advanced age	PAS stain +ve	Lipofuscin. (WC)

Large duct obstruction

Histologic findings of large-duct obstruction:

1. Perivenular bilirubinostasis.
2. Portal tract edema & inflammation (neutrophils & macrophages).
3. Large bile plugs.
4. Bile duct proliferation.

Note:

• Ductular reaction = increased number of ducts + neutrophils.

Small duct obstruction

Small-duct obstruction:

• Abnormal liver plate architecture. (???)

Images

• 

  Cholestasis. (WC/Nephron)

www:

• Centrilobular cholestasis (humpath.com).

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LIVER, CORE BIOPSY:
- CENTRILOBULAR CHOLESTATSIS (MILD), SEE MICROSCOPIC DESCRIPTION AND COMMENT.
- NEGATIVE FOR FIBROSIS.

COMMENT:
There is no apparent feathery degeneration. There is no bile ductular proliferation. No
definite onion-skin lesions are identified.

The centrilobular distribution of the bile favours a large duct obstruction. Possible
causes include gallstones, other obstructing lesions, herbals and drugs.

Clinical and radiologic correlation is suggested.

See also

• Ballooning degeneration.
• Drug-induced liver injury.