Hepatocytes are the epithelial cells of the liver, and these are the main targets of most liver diseases. They can ultimately undergo necrosis, a form of cell death, after lethal injury. This can occur following severe metabolic disturbances, toxic insults, nutritional deficiencies and through the action of micro-organisms.
Despite many types of injury that the liver is subjected to, the resultant necrosis occurs in one of three patterns:
Random Necrosis (Focal)
In this form of necrosis, there is no distinct pattern of lesions - small foci of necrosis are randomly scattered throughout the liver, and may be either microscopic or just visible to the naked eye. They can result from a variety of insults such as - systemic viral, bacterial and parasitic infections, or as a result of bacteria being absorbed from the gut.
Examples of conditions that result in random focal hepatic necrosis include:
- Equine herpes virus 1 infection found in aborted foetuses
- Septicaemia in association with salmonellosis, tularaemia and listeriosis
- Toxoplasmosis in dogs and cats
If grossly visible, necrotic foci appear as discrete white or red foci that range from one to many millimetres in diameter.
This type of change affects hepatocytes in defined anatomic regions of the liver lobule:
This is the most common type of zonal necrosis and occurs mainly due to the fact that hepatocytes in this central zone are furthest away from the incoming blood supply. They are therefore more susceptible to hypoxia. Additionally, they contain the greatest concentration of cytochrome p450 enzymes that metabolise substances into more reactive metabolites capable of killing the hepatocytes. Therefore toxic insults and conditions leasing to hypoxia commonly produce this pattern of necrosis. Some viral conditions, however, also result in centrilobular necrosis, such as Infectious Canine Hepatitis (ICH). This is a highly infectious disease of young dogs caused by canine adenovirus-1. It is now rare in the UK and US due to effective vaccination protocols.
This pattern of necrosis is rare in animals although is mainly seen in horses and pigs with aflatoxicosis. It is also seen in people suffering from 'Yellow Fever'.
This is another uncommon pattern of necrosis that only involves a region around the central vein. It is caused by direct-acting hepatotoxins, and is seen in cases of phosphorus poisoning.
Regardless of the zone affected, grossly the liver is pale, friable, slightly enlarged with rounded edges, and has an enhanced lobular pattern.
This pattern does not imply necrosis of the whole liver, but rather describes necrosis that spans an entire lobule or adjacent lobules. All hepatocytes within the affected lobule(s) are necrotic.
Since all hepatocytesin the lobule are affected, regeneration of these regions is not possible, and affected lobules collapse. In acute stages, the liver may be enlarged or swollen due to congestion. Later, it may reduce in size as a result of scarring that occurs subsequent to lobular collapse (post-necrotic scarring).
Hepatosis dietica is one condition that results in massive necrosis due to vitamin E and selenium deficiency. This occurs in rapidly growing pigs that are fed on large quantities of grain concentrates, or poor quality or low quantity protein supplements. The exact pathogenesis is still poorly understood, but the resultant nutritional deficiencies of selenium and Vitamin E are considered to generate free radicals that result in liver necrosis.
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McGavin, M.D. and Zachary, J.F. (2007) Pathologic Basis of Veterinary Disease (Fourth Edition), Elsevier Mosby.
Nelson, R.W. and Couto, C.G. (2009) Small Animal Internal Medicine (Fourth Edition), Mosby Elsevier.
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This article has been expert reviewed by Dr. Nicola Parry BVSc, MSc, DipACVP
Date reviewed: September 09, 2011