Cirrhosis

Introduction

Cirrhosis represents an “end-stage liver” - the final, irreversible result of diffuse hepatic disease, involving architectural disruption of the entire liver. Underlying chronic injury leads to loss of hepatic tissue with replacement fibrosis. Nodular regeneration occurs within regions of hepatic tissue in between fibrous tissue bands, giving rise to the characteristic multinodular gross appearance of this condition.

The three characteristic microscopic features of cirrhosis are:

• Nodular regeneration
• Fibrosis
• Bile duct hyperplasia

Bile duct hyperplasia around portal regions is a non-specific response to a variety of long-standing hepatic insults, but occurs especially in association with diseases that obstruct bile drainage.

Vascular abnormalities are also associated with cirrhosis. Anastomoses occur between the hepatic portal vein and systemic vasculature due to increased portal pressure. Additionally, vascular shunts can result within regenerative nodules, either between central and portal veins, or between hepatic arteries and central veins.

Causes of Cirrhosis

Some of the many possible causes of cirrhosis in animals include:

• Chronic right sided heart failure
• Chronic hepatitis
  • Lobular dissecting hepatitis in dogs
  • Hepatitis due to infectious canine hepatitis virus
• Chronic cholangitis or bile duct obstruction
• Chronic toxicity
  • Pyrrolizidine alkaloid plants in herbivores
  • Primidone anticonvulsants in dogs
• Inherited diseases of metal metabolism
  • Copper (Dalmatians, Bedlington terriers, West Highland white terriers)
  • Iron metabolism

Cirrhosis is usually the end result of multiple pathological processes, in particular cell death and active inflammation with fibrosis. Regardless of the original underlying aetiology, however, the end-stage liver can no longer perform its functions, and is therefore associated with clinical manifestations of hepatic failure.

References

Blood, D.C. and Studdert, V.P. (1999) Saunders Comprehensive Veterinary Dictionary (2nd Edition), Elsevier Science.

Ettinger, S.J. and Feldman, E.C. (2000) Textbook of Veterinary Internal Medicine Diseases of the Dog and Cat Volume 2 (Fifth Edition), W.B. Saunders Company.

Maxie, M.G. (2007) Pathology of Domestic Animals Volume 2 (Fifth Edition), Elsevier Saunders.

McGavin, M.D. and Zachary, J.F. (2007) Pathologic Basis of Veterinary Disease (Fourth Edition), Elsevier Mosby.

Smyth, B (2008) Alimentary System Study Guide, Royal Veterinary College.

• a term often used for fibrotic lesions, especially widespread fibrosis
• it is an end stage liver with poor functional ability
• much debate on the definition and classification of cirrhosis
• in any case the following conditions prevail:

1. the whole liver is involved

2. cellular necrosis occurs at some stage in the disease

3. there is nodular regeneration of liver cells

4. fibrosis occurs and is diffuse

5. there is disorganisation of the lobular architecture, with fibrous tracts joining portal triads and central veins

6. clinically it is a chronic disease

7. liver cell failure always supervenes and portal hypertension is often a feature

Aetiology

• precise aetiology is unknown
• as in man, may be due to viral hepatitis in Rubarth's disease (ICH)

Gross

• smaller than normal
• firm to cut
  • firmness is due to the presence of fibrous tissue
• pale, sometimes yellow in colour
• regenerating nodule
  • can be small and even in size with the liver having a finely granular appearance
  • or much larger, uneven in size, and the liver surface is deeply fissured and irregular

Microscopically

• exhibits all 3 responses to injury
  • nodular regeneration of the parenchyma
    • haphazard regeneration of liver cells forming islands of new cells surrounded by condensed portal areas
  • fibrosis
    • early cases show areas of fibrosis connecting two or more portal triads
    • later cases have prominent laying down of cartilage
  • biliary hyperplasia

Effects of cirrhosis

due to

• liver cell failure
• development of portal hypertension
  • displacement and compression of efferent veins
    • fibrous connective tissue bands enclose veins and constrict them by contraction
    • regenerating nodules of liver cells contribute as well
  • abnormal communications open up between arterial and venous branches
  • this transmits high arterial pressure directly to the low pressure venous system

Sequelae

the rise in the venous pressure leads to the development of an accessory portal circulation and contributes to the development of ascites

• prominent collateral pathways form in an attempt to circumvent the portal obstruction

1. via the intercostal veins to the azygous

2. via the gastric veins through the oesophageal veins also to the azygous

3. various venous plexuses, draining back into the renal vein

4. several prominent subcutaneous veins are also seen, running radially from the umbilicus over the abdomen

NB: oesophageal and gastric collaterals in the dog run subserosal, not submucosal like man, therefore they are not as subject to traumatic rupture

• ascites
  • common finding
  • other factors are involved: lowered plasma albumin, causing lowered colloid osmotic pressure