Category:Liver - Inflammatory Pathology

Types of Inflammation

Hepatitis, Chronic

Cholangitis

Cholangiohepatitis

• both parenchyma and bile ducts are inflamed

Cholecystitis

• inflammation of the gall bladder

Infectious Agents

Viral

Infectious Canine Hepatitis

• adenovirus
• also known as Rubarth's Disease, Canine adenovirus infection
• acute and generalised infection
• young dogs
• highly infectious
• spread via the urine of infected animals over a long period of time

Clinical

• lymph nodes and tonsils are enlarged and reddened, sometimes haemorrhagic
• recovering animals may show an immune-mediated uveitis with corneal opacity

Gross

• the virus has a tropism for endothelium and hepatocytes
  • widespread haemorrhages, especially on serosal surface
• distinctly pale mottled appearance
  • from extensive necrosis, characteristically periacinar (centrilobular) in distribution - the reason for the increased susceptibility of this area is not known
• enlarged
• friable
• fibrinous or fibrino-haemorrhagic strands between lobes
• gall bladder
  • wall usually shows oedema (up to 2cm diameter)

Microscopically

• basophilic intranuclear inclusion bodies
  • in hepatocytes and macrophages

Herpes virus infections

• includes
  • Equine Viral Rhinopneumonitis
  • Infectious Bovine Rhinotracheitis
  • Feline Viral Rhinopneumonitis
  • Aujesky's disease in pigs
• in addition to their effects on adults, these viruses cause abortion with characteristic pinpoint foci of necrosis in the foetal liver

NB: Look for the intranuclear inclusions in surrounding surviving hepatocytes

• canine herpes virus
  • causes similar lesions in young puppies
  • mostly in kidney, spleen, and lung

Feline Infectious Peritonitis

• coronavirus
• causes pyogranulomatous lesions on the surface of many organs including the liver

Bacterial

• bacteria can enter the liver through a variety of routes
  • direct implantation
    • eg foreign body penetration from reticulum
  • direct extension from disease in adjacent tissues of supportive peritonitis
  • haematogenously
    • via the umbilical vein from an infected umbilicus
    • via the portal vein in the alimentary tract
    • via the hepatic artery in bacteraemias and septicaemias
    • via the bile ducts
• the liver may show microscopic evidence of involvement in a large variety of systemic infections
• these can be accompanied by jaundice
• the changes in the liver are diffuse with many small areas of necrosis surrounded by neutrophils and lymphocytes
  • eg Salmonellosis or Listeriosis

Hepatic abscessation

• with supportive hepatitis
• especially common in cattle and sheep

Causes

• bacteria involved
  • Fusobacterium necrophorum 80% +
  • Arcanobacterium pyogenes
  • Streptococcus
  • Staphylococcus
  • Bacteroides
• spread from umbilicus in young animals
  • omphalophlebitis (navel ill)
  • usually mixed bacteria
    • Actinomyces pyogenes
    • Staphylococci (predominates)
• haematogenously from other pyaemic source
  • eg metritis or mastitis
  • bacteria invade ruminal wall and enter portal circulation to liver
• from rumenitis caused by overfeeding with grain
  • erosion of ruminal epithelium due to acidosis

Clinical Signs

• subclinical
• detected at exploratory laparotomy or sluaghter
• weight loss (most important)
• decreased weight gain or milk yields
• sporadic fever and anorexia

NB: animals can appear in good health as long as abscesses do not rupture

Gross

• large
• pale greenish-yellow pus
• thick fibrous capsule

Sequelae

• variable
  • resorption and healing
  • abscess may extend into the heaptic vein
    • give rise to thrombosis in the caudal vena cava
    • possible pulmonary abscesses
    • endocarditis
  • fibrous adhesion to adjacent viscera
    • if the abscess is near the surface
  • epistaxis, sudden death

NB: in many cases, abscesses are incidental findings at slaughter and result in condemnation of the affected livers

Bacillary necrosis

• Fusobacterium necrophorum
• calves and lambs
• common in intensively reared beef cattle
• occurs following an infected umbilicus in neonates and from rumenitis in adult cattle

Gross

• rounded pale multiple foci of coagulative necrosis throughout the liver
• unsoftened, greyish-yellow patches
• ringed by a zone of hyperaemia
• foci coalesce in severe cases
• in adult animals, these lesions may have progressed to abscesses following lysis of the coagulated necrotic tissue and the formation of fibrous capsule around the damaged tissue
• if animal survives, these lesions may soften develop into abscesses

Microscopically

• coagulative necrosis
• possible evidence of migrating flukes
• bacteria can be demonstrated in the periphery of the necrotic tissue, especially near its junction with viable tissue
• there is a rim of neutrophilic cells

Infectious Necrotic Hepatitis (Black Disease)

• Clostridium novyi type B
• grazing animals
  • mainly sheep, also cattle (and reported sometimes in horses and goats)
• organism is widely distributed within the soil and normally present in GIT and liver of grazing animals on infected pastures
  • worldwide
• it is ingested by the animal and spores are absorbed via the gut and travel to the liver , where they lie dormant in macrophages (Kupffer cells) - also found in bone marrow and spleen
• seasonal disease associated with Fasciola liver flukes
  • migrating immature liver flukes precipitate the disease
  • causes liver damage which provides ideal anaerobic conditions for the activation and germination of spores
• C. novyi produces three exotoxins
  • alpha - a lethal toxin
  • beta - a lecithinase which is both haemolytic and necrotising
  • zeta - a haemolytic toxin
• acute toxaemia produced by organism
  • affected animals are usually found dead because death is sudden due to the action of the powerful bacterial endotoxins
  • not all animals will become sick - only when organism starts producing toxin
• post mortem changes occur rapidly

Clinical

• found dead/sudden death
  • well conditioned sheep 2-4 years old
  • lateral recumbency, few signs of struggle
  • vaccination history (against Clostridium)
  • no red urine or other bleeding
• IF seen alive
  • severe depression
  • not eating
  • pyrexia
  • hypothermia
  • respiratory distress
  • muffled heart sounds

Gross

• rapid decomposition of carcass
• extensive subcutaneous vessels engorged and haemorrhage causing dark colouration of the skin - hence the name 'Black Disease' - and oedema
• blood stained fibrinous fluid in abdomen, thorax, and pericardium which clots on exposure to air
• tissues are autolysed
• liver swollen and congested
• characteristic pale (greyish-yellow) foci (3cm diameter) of necrosis surrounded by a rim of haemorrhage where the bacteria have multiplied upon incision
• evidence of liver fluke
• other organs show general signs of toxaemia

NB: Distinguish Black Disease from Red Water! The former will have several small areas of necrosis while the latter has one big lump

Microscopically

• coagulative necrosis
• possible evidence of migrating flukes
• demonstration of bacteria
  • in the necrotic tissue
  • especially near its junction with viable tissue
  • rim of neutrophilic cells

Treatment

• rarely possible
• Penicillin or Oxytetracycline at very high doses

Prevention

• vaccination
  • normally lasts up to 6 months
• liver fluke control
• remove dead carcasses from pasture

Bacillary Haemoglobinuria (Red Water)

• Clostridium haemolyticum AKA Clostridium novyi Type D
• cattle and sheep
• highly fatal
• similar pathogenesis to C. novyi
• beta toxin produced
  • causes hepatic necrosis and intravascular haemolysis
• C. haemolyticum found in soil, poorly drained/wet pastures
• spores found routinely in liver and GIT and faeces of grazing animals in affected pastures
• need disease in liver casing anaerobic conditions to allow bacterial growth and toxin production
• normally associated with Liver Fluke damage
• disease occurs in some areas and some farms - distribution is poorly understood

Clinical Signs

• found dead/sudden death
  • lateral recumbency
  • bloat
  • little signs of struggle
  • blood in nostrils, mouth, rectum, vagina
• IF seen alive
  • depressed, reluctant to move, pyrexia, respiratory distress
  • red urine (haemoglobinuria) but not consistent
  • pale mucous membranes/jaundice
  • bloody froth in nostrils

Gross

• post mortem is confirmatory finding
• rapid decomposition of carcass
  • organs decomposed
• subcutaneous hameorrhages, odema, emphysema
• blood stained abdominal and thoracic fluid, large quantity and pericardium
• animal is severely anaemic
• may be jaundiced
• red urine in bladder, therefore haemoglobin in urine
• kidneys speckled with haemoglobin
• blood in lungs/trachea
• ischaemic hepatic infarct
  • usually a single large necrotic focus in the liver
  • area of necrosis, sometimes partially liquefied centre, irregular outline with a hyperaemic edge

Microscopically

• presence of Clostridia post mortem must be interpreted with great caution as they are common post mortem invaders
• FAT for organism
• identification of toxins
  • need this for diagnosis

Treatment

• unlikely
• very high doses of penicillin or oxytetracycline
• blood transfusion

Prevention

• vaccination lasts up to 6 months
• liver fluke control
• remove infected carcasses from pasture

NB: Distinguish Red Water from Black Disease! The former will have bleeding out of any orifice while the latter does not

Tyzzer's disease

• Bacillus piliformis
• affects
  • mostly laboratory rodents
  • possibly foals 1-4 weeks of age
  • young immune-compromised pups and kittens
• initial intestinal lesions can be hard to find at post mortem examination

[image from smythes' ppt] wheat sheaf

Leptospirosis

• Leptospirosis icterohaemorrhagica - a septicaemic disease which affects the liver
• puppies
• Leptospirosis is an important spirochaetal group of diseases causing disease in animals and humans (zoonotic)
• Transmission
  • via urine of affected animals
  • organisms can remain viable for weeks in damp conditions
• method of action
  • cause anaemia via intravascular haemolysis

Clinical

• fever
• dehydration
• haemorrhaging from the mucous membranes of the body

Diagnosis

• dark field microscopy on fresh urine is best

Gross

• widespread hameorrhages
• icterus
• pale foci in the liver (not always a constant finding)
• subcapsular and cortical renal haemorrhages

Microscopically

• foci of necrosis
• dissociation of hepatocytes form each other (similar to post mortem change)
• substantial haemosiderin in the Kuppfer cells (from the haemolysis)
• need to use a silver stain or immunofluorescence to demonstrate the organisms in tissues

Salmonellosis

• Salmonella dublin
• calves

Clinical

• fever
• dehydration
• diarrhoea

Gross

• severe, often haemorrhagic, inflammation in the ileum
• paratyphoid nodules - pale foci of necrosis in the liver

Microscopically

• foci of hepatocytic necrosis
• mixed mononuclear inflammatory cell infiltrate

NB: small foci of hepatocytic necrosis are often found as incidental lesions at post mortem examination

Other bacteria causing liver lesions

Mycobacterium tuberculosis

• in all species
• causes granulomas

Actinobacillus equuli

• foals
• bacteria from the septicaemia localise in the liver and other tissues, including the kidney

Nocardia species

• dogs
• cause pyogranulomatous foci

Parasitic

Many parasites pass through the liver as part of their life cycle within the host

Some migrate further to other organs while others remain in liver tissue, especially the bile ducts

Most migrating parasites escape the liver but occasionally some may die and provoke a granulomatous reaction that may calicfy later

The following are types of parasites causing liver lesions:

Nematodes

• these cause damage during migration through the liver

Ascaris suum

• Ascariasis
• 'milk spot' liver
• pigs
• common incidental finding at post mortem examination
• affected livers are condemned at meat inspection

Gross

• initial haemorrhagic tracts through the liver attributed to the migration of ascarid larvae
• later stages show fibrosis of these tracts as poorly defined, diffuse, white spots on the capsular surface

Microscopically

• initial haemorrhage and necrosis of parenchyma along the tracts
• later repair by fibrous tissue at foci
• inflammatory cell response contains many eosinophils, as well as lymphocytes and macrophages

Strongyles

• horses
• it is common to find fibrous tags incidentally on the liver surface and adjacent diaphragm
• these are remnants of fibrous repair following the egress of the parasites from the liver

Cestodes

• tapeworms
• have both intermediate and final hosts in their life cycle
• main expression in the UK are the encysted forms that utilise the liver and other organs in intermediate hosts

Taenia hydatigena

• the most important species
• final host
  • dog
  • alimentary tract
• intermediate host
  • ruminant, horse, or pig
• life cycle is completed when the carnivore eats the tissues of the intermediate host containing the cysts
• the intermediate stage - Cysticercus tennuicollis
  • fluid filled cysts on the surface of the liver and in the peritoneal cavity

NB: other Taenia species have muscle and brain as preferred sites in the intermediate hosts

Some can infect humans - zoonoses

Echinococcus granulosus

• Hydatid Disease
• final host
  • dog, fox, and other canids
• intermediate host
  • sheep most commonly affected
  • ox and horses

NB: can also affect man - zoonosis

• hydatids - the cyst form
  • develops from the ova
  • occur in the lung and liver
  • cysts are usually multiple
  • 5-10cm in diameter
  • contain a clear fluid with numerous scolices or "hydatid sand"
  • the small calcified lesions that are sometimes present in the liver of sheep may represent degenerate hydatid cysts
  • can be very prevalent in some geographical areas

Trematodes

• flukes are important pathogens of the liver
• Fascioliasis is among the most important parasitic conditions of sheep and cattle and is common

Fasciola hepatica

• common liver fluke
• intermediate host
  • aquatic snails
  • therefore infestation is more common in damp or poorly drained pastures
• final host
  • cattle and sheep
• can cause severe haemorrhagic liver damage
• death in heavy infestations in sheep during migratory phase (1 month) through the liver tissue
• recovered animals will have scarred livers
• more commonly associated with chronic bile duct inflammation - cholangitis [need link to below]
  • the adults live in the bile ducts

Acute Fascioliasis

• acute disease associated with immature fluke migration through the liver
• occurs in late autumn and winter
• severity of outbreaks depend on a number of epidemiological factors
• the liver of animals which die of this disease will be
  • enlarged
  • haemorrhagic
  • honeycombed with the tracts of migrating flukes
    • tracts become filled with blood and degenerate hepatocytes later infiltrated with eosinophils, lymphocytes and replaced by fibrosis
  • surface is covered with a fibrinous peritonitis, especially the ventral lobe
  • subcapsular haemorrhages are frequent
  • rupture into the abdomen is not an uncommon finding

Chronic Fascioliasis

Gross

• liver is reduced in size, unevenly
  • left lobe is most severely affected with atrophy of the extremities
• hypertrophy may occur in some cases
  • dorsal lobe
  • this changes size and distorts shape of liver
• the surface will be uneven with areas of fibrous tissue replacing the cells damaged by the migrating flukes
• bile ducts
  • prominent thick protruding white bile ducts on the visceral surface spreading from the hilus to the left lobe
  • the bile ducts are dilated, black, and calcified on cut surface
  • numerous adult flukes can be expressed from the bile ducts
  • chronic cholangitis
  • 'pipe stem' appearance in cattle because bile ducts are very much thickened and often calcified
• bile
  • dark brown, thick, and gritty in consistency

NB: the fibrosis which occurs in the chronic stage is realted only partly to the healing of the migratory tracts and the rest may be related to the development of immunity and rechallenge

Microscopically

• reactive hyperplasia of the bile ducts
• substantial inflammatory cell infiltrate and peripheral fibrosis
• calcification of the chronically damaged tissue

Protozoal

Toxoplasmosis

• Toxoplasma gondii
• broad host range
• characterised by widespread necrosis in many organs
• liver lesions
  • appear as disseminated foci of necrosis with little or no inflammatory reactions
  • white or yellow foci are visible on the surface

Peliosis hepatica

• Dogs and cats
• Vasculoproliferative disorder – cystic, blood filled spaces in the liver , surrounded by fibromyxoid matrix containing inflammatory cells and dilated capillaries.
• Spaces may merge with hepatic sinuosoids.
• May be associated with Bartonella henselae infection.
• Natural host is the cat
• Transmitted between cats by fleas
• Cause of cat-scratch fever and bacillary angiomatosis in humans

Lobular dissecting hepatitis

• Rare cause of chronic liver failure in young dogs
• Less than 5yrs of age
• Standard poodle overrepresented
• Gross findings:
  • Micronodular microhepatica, ascites, numerous portosystemic shunts
• Histology:
  • Hepatic architecture disrupted by collagen and reticulin fibres separating the hepatic lobules into small clusters and individual cells
  • Hepatocytes mutlifocally swollen, lightly eosinophilic, some binucleated.
  • Variable nodular regeneration.
  • Scattered necrotic cells and occasional foci of inflammation.
• Cu2+ accumulation not a consistent finding.
• Aetiology – possibly a specific reaction pattern in neonatal/juvenile liver .
• Differentials:
  • Copper toxicity
  • Copper storage disease
  • Aflatoxin
  • Infectious diseases such as Leptospria spp. and CAV-1.

Hepatitis in cats

• 2 main types
  • cholangiohepatitis
    • cholangitis
    • periportal hepatocellular necrosis
    • neutrophils in the portal areas
    • acute or chronic.
    • Usually male, pure bred
    • Cats more ill than lymphocytic portal hepatitis.
    • Higher ALT and serum bilirubin levels.
  • Lymphocytic portal hepatitis
    • infiltration of portal areas with lymphocytes and plasma cells
    • no cholangitis
    • no periportal hepatocellular necrosis.