Liver Necrosis

Introduction

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.

Zonal Necrosis

This type of change affects hepatocytes in defined anatomic regions of the liver lobule:

Periacinar (Centrilobular)
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.

Midzonal
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'.

Periportal (Centroacinar)
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 enlargedwith rounded edges, and has an enhanced lobular pattern.

Massive Necrosis

This occurs when there is necrosis of a complete acinus or an even larger area of tissue. It encompasses large areas of liver cells comprising many lobules (complete acinus or several acini) and sometimes involving almost the whole organ.
It can occur is some cases of ICH infection or carbon tetrachloride poisoning, with the severity of the injury replacing the zonal pattern.

Subacute Cytolytic Necrosis

This is a condition in the dog, of which the aetiology is entirely unknown. Clinical symptoms include acute abdominal pain, collapse and invariably jaundice. Pathology shows the liver is normal or reduced in size and that there is severe necrosis.

Hepatosis dietica

This is a similar condition to subacute cytolytic necrosis, but it occurs in rapidly growing pigs. It is thought to be related to diet and occurs in pigs fed on large quantities of grain concentrates, poor quality or low quantity protein supplements. This results in nutritional deficiencies of selenium and Vitamin E, and probably amino acids. It is thought to be triggered by stress.

Liver Necrosis Learning Resources
Flashcards Test your knowledge using flashcard type questions	Liver Pathology Flashcards

References

Blood, D.C. and Studdert, V. P. (1999) Saunders Comprehensive Veterinary Dictionary (2nd Edition), Elsevier Science.
Ettinger, S.J, Feldman, E.C. (2005) Textbook of Veterinary Internal Medicine (6th edition, volume 2), W.B. Saunders Company.
Fossum, T. W. et. al. (2007) Small Animal Surgery (Third Edition), Mosby Elsevier.
Nelson, R.W. and Couto, C.G. (2009) Small Animal Internal Medicine (Fourth Edition), Mosby Elsevier.