Difference between revisions of "Category:Liver - General Pathology"

Liver Failure

Syndromes in liver failure

Jaundice (Icterus)

• this is a staining of the tissues with bilirubin or bilirubin complexes
• bile pigments have a strong affinity for elastic tissue and thus the yellowish colour can be easily seen in the sclera and mucous membranes in life and in the aorta at necropsy
• the serum bilirubion level gives an indication of the degree of icterus
  • dog's normal range is usually below 0.5mg/100ml
  • level is at least 2mg/100ml when jaundice is clinically evident

Causes

• overproduction of bilirubin
  • eg haemolytic crises
• diffuse liver disease
  • where there is a decreased uptake, conjugation, and secretion of bilirubin
• reduced outflow of bile into the gut
  • intrahepatic biliary obstruction eg foreign bodies, tumours, or fibrosis

Classification types

Haemolytic jaundice

• due to increased red cell destruction
  • results in increased amounts of bilirubin in the reticuloendothelial system
  • the production may be at a rate which exceeds the capacity of the liver to conjugate and eliminate it
• most of bilirubin is unconjugated
• bile pigment is not excreted in the urine
  • since the kidney can excrete only the water soluble conjugate
• diseases
  • Babesiosis
  • isoimmune reactions eg newborn foal whose dam has elaborated specific antibody against its red cells

Obstructive jaundice

• due to bile duct obstruction
• accumulation of conjugated bilirubin
• bile pigment is excreted in the urine
• bile pigment will be diminished in the faeces
• diseases
  • carcinoma involving the head of the pancreas

Hepatocellular jaundice

two factors are concerned in the production of jaundice following liver cell damage

• damage to liver cells can interfere with the passage of bile along the bile capillaries
  • eg intrahepatic obstruction
• Liver cell damage may cause failure of conjugation and therefore excretion failure of bile pigment

Photosensitisation

• 'sunburn-like' lesions
• cattle and sheep
• sharply confined to the unpigmented areas of the skin
• occurs as a result of the effect of strong sunlight
  • due to the effect of UV light on a photodynamic agent (PDA) present in the skin, such as is phylloerythrin derived from chlorophyll
  • therefore, the disease occurs mostly in those animals consuming large quantities of grass
  • the UV light is changed to a longer wavelength which produces the necrosis of the skin
• many unknown/poorly understood causes
  • feeding rape, kale, lucerne, alfalfa
  • mouldy hay
  • lush pasture
  • corticosteroid induced

Primary photosensitisation

Causes

• normal ingestion of growing lush green plants containing PDA
  • plants containing such fluorescent pigments
    • Hypericum perforatum (St John's Wort) - active principle is hypercin
    • Lolium perenne (Perennial Rye Grass) - active principle is perloline
• drugs
  • phenothiazine
  • thiazides
  • tetracyclines
  • sulphonamides
• inherited porphyria

Secondary photosensitisation

• photosensitisation secondary to liver damage

Cause

• hepatogenous photosensitisation
  • chlorophyll is metabolised to phylloerythrin
  • when the liver or bile ducts are malfunctioning (eg hepatitis or bile duct obstruction) due to severe toxic damage, phylloerythrin escapes into the circulation and settles in the tissues including the skin
  • the pigment accumulates causing photosensitisation
• hepatotoxic plants
  • Senecio jacobea (Ragwort)
  • Lantana camara (Lantana)
  • Lupinus angustifolius (Lupins)
  • Blue-green algae

Clinical Signs

• localised to lightly pigmented skin areas
• clear cut demarcation of affected area
• teats, muzzle, ears
• skin only
• skin and liver signs

Microscopically

• subepidermal vesicles
  • ulcerate
  • become secondarily infected

Treatment

• remove from sunlight

Hepatic Encephalopathy

Clinical

• non-specific neurological signs (attributed to the retention of ammonia and gamma aminobutyric acid in liver failure and their effects on the brain)
  • dullness
  • apparent unawareness of surroundings
  • pointless or compulsive movements
  • mania
  • generalised convulsions

NB: usually soon followed by death

Microscopically

• lesions in the brain vary in expression
  • most species may show myelin degeneration consisting of vacuoles between the grey and white matter
  • the horse may show very little visible neural changes, perhaps an increase in astrocytes

Causes

Portosystemic Shunting

Chronic liver damage

• due to ingestion of toxic compounds over a long period of time
• E.g. ragwort

Bleeding Tendencies

• in acute liver damage
• there is substantial necrosis of the liver tissue even though it may not be pronounced on gross inspection
• there is contact of blood with the damaged liver parenchyma which triggers the clotting cascade, consuming the circulating clotting factors - have a short half life
• since the liver is also responsible for the production of these clotting factors, there is an acute shortage and an animal dying from such acute liver damage may show petechial and ecchymotic haemorrhages in many organs of the body
• see Canine Viral Hepatitis (ICH)
  • gross and microscopic appearances - haemorrhages will be seen in many tissues in this disease, particularly on the intestinal serosa

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