Category:Liver - General Pathology

Liver Failure

Syndromes in liver failure

Icterus

Photosensitisation

Hepatic Encephalopathy

Bleeding Tendencies

Hypoalbuminaemia

• in chronic liver damage
• Liver will be unable to synthesise plasma proteins
  • especially albumin
  • this leads to oedema in body tissues and cavities due to lowering of the colloid osmotic pressure in the circulation
• most common in dogs and cats

Liver response to injury

• Again, the liver is liable to injury from many causes and this is especially the case for a number of reasons
  • position
    • the liver acts as a second barrier between the non-sterile intestinal contents and the systemic circulation
    • is exposed to viruses, bacterial toxins, and poisons absorbed from the portal blood
  • energy requirements
    • relatively enormous amounts of energy are utilised by liver cells and this renders them more vulnerable to anoxia and toxaemia
  • detoxification
    • the liver acts as a detoxifying organ and may suffer in consequence

Necrosis

Causes

• severe metabolic disturbances [as seen in degenerative pathology link?]
• toxic substances [link?]
• nutritional deficiencies
• action of micro-organisms

Histological patterns

• Liver cell necrosis has been classified on an anatomic basis with reference to the distribution of the lesion

Random foci (focal)

• microscopic foci of necrosis not related to any particular part of the liver lobule
• can be due to a variety of insults
  • systemic viral, bacterial,and parasitic infections
  • result of bacteria being absorbed from the gut
• examples
  • Equine herpes virus infection
    • in aborted foetuses
  • Salmonellosis
    • in calves
  • Toxoplasmosis (miliary)
    • in dogs and cats

Zonal necrosis

• necrosis occurring mainly in a part of the lobule and further subdivided according to whether the lesions are situated centrally, peripherally, or in the mid-zone of the lobule
• due to anoxia

Periacinar (centrilobular)

• most common
• main reason is because the hepatocytes in this zone are furthest away from the incoming blood supply
  • therefore less oxygenated and relatively anoxic
• reported to contain the greatest number of enzymes responsible for metabolising sunstances to more toxic metabolites capable of killing the hepatocytes
• hypoxic states and toxic substances predominate in this type of necrosis
• some viral conditions cause this necrosis
  • eg Infectious Canine Hepatitis
• poisons
  • eg carbon tetrachloride

Midzonal

• rare
• in pigs with alfatoxicosis
• 'Yellow Fever' in man

Periportal (centroacinar)

• rare
• eg phosphorous poisoning

Massive necrosis

• necrosis of large areas of liver cells comprising many lobules (complete acinus or several acini) and sometimes involving almost the whole organ
• some cases of ICH infection or carbon tetrachloride poisoning, the severity of the injury replacing the zonal pattern

Subacute cytolytic necrosis

• a condition in the dog
• aetiology is entirely unknown
• Clinical
  • acute abdominal pain
  • collapse
  • invariably jaundice
• Gross
  • Liver is normal or reduced in size
• Microscopically
  • severe necrosis

Hepatosis dietica

• similar condition to subacute cytolytic necrosis
• occurs in rapidly growing pigs
• related to diet
  • fed on large quantities of grain concentrates
  • poor quality or low quantity protein supplements
• Cause
  • nutritional deficiencies of selenium and Vitamin E, and probably amino acids
  • triggering mechanism is environmental stress

Regeneration

• occurs quite readily when damaged
• approximately 70% of the liver can be removed surgically without danger to life
  • can reconstitute itself to its former mass in a few weeks
  • may not be its original shape

NB: larger areas of necrosis or continual bouts of necrosis are accompanied by fibrosis and biliary hyperplasia [link to the last two terms]

Fibrosis - Repair

• any hepatic injury of consequence is going to cause a degree of fibrosis when the lesion has resolved
• the fibrosis comes from the proliferation of the supportive connective tissue in the liver
• fibrosis isolates the liver cells by effectively changing the sinusoids into capillaries
• when a certain amount of fibrosis occurs, it can be self-perpetuating
  • the end result is a small scarred liver with functional failure

Histological patterns

Periacinar fibrosis

• the fibrosis surrounds the hepatic venule (centrilobular vein)
• can be seen when there is chronic passive congestion with atrophy of the surrounding periacinar hepatocytes and condensation of the remaining connective tissue

Biliary fibrosis

• accompanying inflammation centered on the portal triads

Post necrotic scarring

• following massive necrosis where the necrotic cells are removed and the defect is reapired by fibrosis
• seen as bands of fibrous tissue

Diffuse fibrosis

• resulting from repeated damage to one or more zones
• the fibrosis generated proliferates throughout to involve all the tissue

Biliary hyperplasia

• bile duct proliferation
• usually in association with portal fibrosis
• reason is unknown

[image - the picture shows fibroplasias invading between hepatocytes - some of the cells are likely to be distorted bile duct profiles]

Cirrhosis

• 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

Molecular pathogenesis of cholestasis

Hepatic Stellate Cells