Liver & biliary system pathology 3

What are the usual features of a acute bacterial hepatitis?

• Degen / necrosis of hepatocytes → inflam

• Perioportal inflammation —> bacterial infection from GI tract

  • septicaemia

• Neutrophil dominated

Where is acute hepatitis located in the case of septicaemia?

Inflam in sinusoids

What are the features of an acute hepatitis caused by a viral infection?

• Lymphocytic & plasmacytic

• Random pattern

What is the most common cause centrolobular hepatitis?

• Hypoxia/ischaemia

  • If no blood supply you won't get inflam

What is being shown in this image

Acute hepatitis

• Neutrophils dom = blue arrows

• Mononuclear cells

• Pigment = bile —> extracellular

  • bile stasis in caniculi

• Lymphos & macros also

What is being shown in this image

Necrosis during acute hepatitis

Increased leukocytes in sinusoids (diffuse)

What is being shown here?

Perioportal inflammation —> in acute hepatitis

leads to restriction of perioportal system

What are the general features of a chronic hepatitis?

• Predom. periportal infiltration by lymphocytes and plasma cells

• hepatocyte apoptosis/necrosis & some evidence of regen

• progressive periportal fibrosis bridging fibrosis

  

chronic active hepatitis → cirrhosis

necrosis → loss of architecture (reticulin frameworm), fibrosis (blue-staining tissue) & repair

What is chronic active hepatitis?

• Seen in certain breeds —> idiopathic not well understood

  • Doberman hepatitis

  • Cu accumulation in Bedlington terrier

• Determined by quantitiy of inflam & extent of hepatocellular death

• More severe maybe

• May see neutrophils as well

• Can progress to cirrhosis (end stage)

How does chronic hepatitis present histologically?

• Areas of fibrosis

• Marked degen of hepatocytes

• Pigment accumulation

• Hydropic degeneration = entry of fluid into hepatocytes

• Mononuclear infiltration

What is being shown here?

Cholangiitis / cholangiohepatitis = inflam originating from biliary tree

What is cholangiohepatitis?

Inflam originating from the biliary tree AND liver

When may you see cholangitis/cholangiohepatitis?

• Chronic fascioliasis

• Eimeria in rabbits

• Biliary mucocoele (change in gall bladder of dog causing bile stasis)

• Feline “triaditis”

What is feline triaditis?

Associated with three inflammation

• IBD

• Chronic pancreatitis

• Feline cholangitis (inflam of bile duct system)

What are the clinical findings associated with feline cholangitis?

ascites, jaundice, polyphagia, weight loss

What are the three characteristic histological stages of feline cholangitis?

1. Suppurative cholangitis / cholangiohepatitis

2. Lymphocytic and plasmacytic periportal infiltration (1) bile duct hyperplasia and periportal fibrosis (2)

   

3. Biliary cirrhosis (2) [= end stage] (severe porto-portal fibrosis, bile duct hyperplasia (1), nodular hepatic hyperplasia)

   

List some examples of viral hepatitis

1. Infectious canine hepatitis [CAV-1; adenovirus]

2. Equine herpesvirus infection [EHV-1]

3. Canine herpesvirus infection [CaHV-1]

4. Rabbit haemorrhagic disease [RHDV-1 and -2; calicivirus]

5. Feline calicivirus (FCV)

6. Feline infectious peritonitis [FCoV; coronavirus]

any virus causing viraemia can affect the liver these are just specific

What aetiological agent causes canine hepatitis?

canine adenovirus type 1 [CAV-1]

Describe the pathogenesis of canine hepatitis

• oronasal infection —> tonsils, regional lymph nodes, lymphatics, thoracic duct

• blood (viraemia)

• liver (hepatocytes, Kupffer cells)

• eye (corneal epithelium)

• kidney (glomerular endothelium)

• blood vessels (endothelium)

(vacc against)

What are the different outcomes of canine hepatitis?

• high titre = acute (necrotising) hepatitis —> if survives liver can regenerate

• low titre = chronic, fibrosis, perrsistent infection

What gross lesions are associated with canine hepatitis?

• multifocal haemorrhage (tropism for endothelium → damage)

• fibrin deposition

• oedema of gall bladder

What histological lesions are associated with canine hepatitis?

• Necrotic hepatocytes (red arrows)

  • Centrilobular

• Intranuclear inclusion bodies (black arrows) (can get them in both hepatocytes & endothelial cells) —> chromatin in nucleus pushed to edge

  • seen in periphery of necrosis

What aetiological agent causes equine herpesvirus infection?

Equine herpesvirus 1 [EHV-1], rarely EHV-4

What is the pathogenesis of equine herpesvirus?

• transplacental infection

• uterus (endothelial cells),

• (peri)vasculitis, thrombi → placental detachment → late abortion (7th month)

What organs does equine herpesvirus affect in the fetus?

• Liver

• Lungs

• Thymus

• Spleen (follicles)

• Brain

• Adrenal gland

What gross and histological lesions are associated with equine herpesvirus in the liver?

• Disseminated multifocal necrosis

  

• Disseminated multifocal necrosis, inflammation and intranuclear inclusion bodies (eosinophilic) (less frequent + smaller in herpesvirus than in adenovirus

  

DO PCR TO CONFIRM

What different ages can be infected by canine herpes and how does this impact the pathogenesis of the viral?

• In utero

  • Usually generalised infection fatal before or after birth

• Neonate —> from ingestion, inhalation material in birth canal

  • <1 week generalised infection (viraemia due to not well developed immune system)

  • >2 weeks localised infection and replication —> latency and recrudescence

• Adult (less common)

  • Localised infection and replication —> latency and recrudescence if stressed, immunosuppressed, pregnant…

(can vacc against but not standard vacc)

What aetiological agent causes rabbit haemorrhagic disease?

calicivirus (RHDV-1, RHDV-2)

(can vacc against)

What is the pathogenesis of rabbit haemorrhagic disease?

• faecal-oral infection (highly contagious —> transmitted on fomites)

• (per)acute dx w/ massive necrosis of hepatocytes (virus infects hepatocytes) → sudden death

• DIC in multiple organs (microthrombi e.g. in lung capillaries and renal glomeruli) —> haemorrhage due to reduction in clotting factor production

How does rabbit haemorrhagic disease present grossly?

Multifocal disseminated hepatic necrosis, glomerular hyperaemia

How does rabbit haemorrhagic disease present histologically?

• Hepatic necrosis & calicivirus antigen

How does feline systemic calicivirus present histologically in the liver?

• Hepatitis

stain = virus present

What aetioloigcal agent causes feline infectious peritonitis?

Feline coronavirus (FCoV)

Describe the pathogenesis of feline infectious peritonitis

• oral infection

• infection of enterocytes

• monocyte-associated viraemia

• granulomatous (peri)phlebitis / serositis / hepatitis etc.

How does feline infectious peritonitis present grossly and histoloigcally?

• multifocal granulomatous inflam (in any tissue)

• Perivasculitis

What are the routes of entry of bacteria causing hepatitis?

• the portal vein

• umbilical veins in neonates

• hepatic artery (generalised bacteraemia)

• ascending infection via bile duct / system

• parasitic migration

• direct extension of infection from an adjacent tissue

List examples of bacteria causing bacterial hepatitis

• Enteric bacteria

• Francisella tularensis (tularaemia)

• Nocardia asteroides

• Actinobacillus spp.

• Mycobacterium spp. (tuberculosis)

• Fusobacterium necrophorum (necrobacillosis)

What aetiological agent causes necrobacillosis?

Fusobacterium necrophorum

• [filamentous, gram-negative, anaerobe, commensal in digestive tract]

What is the pathogenesis of necrobacillosis in ruminants?

rumenitis-liver abscess syndrome

• carbohydrate-rich diet → ruminal acidosis

• change in rumen microflora and defects in ruminal mucosa

• access of bacteria to blood vessels and portal vein

• liver —> multifocal necrosis, abscess formation

What is this showing?

• Necrobacillosis

• Multiple abscesses

  • This indicated blood borne infection because of how spread out it is

What aetiological agent causes tularaemia?

Francisella tularensis

• [ZOONOSIS] [pleomorphic, gram-negative, non-spore forming bacillus]

How is francisella tularensis spread?

Ticks

What is the pathogenesis of tularaemia?

inoculation site (skin lesions, tick bite, prey animals: intestine)

localised infection & regional lymphadenitis

bacteraemia, dissemination

What pathology is assocaited with tularaemia?

• ulceration of lymph nodes (or Peyer`s patches with enteric infection),

• necrotising lymphadenitis,

• hepatitis

  

• splenitis

  

What is being shown here?

Yersiniosis

Microabscesses (disseminated, multifocal) in mesenteric LNs, spleen & liver

What aetioloigcal agents causes yersiniosis?

Y. pseudotuberculosis

What has caused this lesion?

• Tuberculosis (M.bovis / M. tuberculosis / M. avium)

  • Disseminated multifocal granulomatous hepatitis

What aetiological agents cause leptospirosis?

Leptospira canicola, L., icterohaemorrhagica, L.grippotyphosa

• [motile, filamentous, spiral-shaped (spirochaetes)]

• Zoonosis

(can vacc against certain strains in dogs)

What is the pathogenesis of leptospirosis?

• Penetration of MM/abraded skin

• Replication in blood

• kidneys, liver, spleen, brain, eyes, genital tract

• serum abs clear spirochaetes from organs, but persistence in renal tubular epithelium can occur

• Transmission via contam water, soil, dirty bedding —> excreted in urine

How does leptospirosis affect the liver in dogs?

• Dysfunction due to cell damage by leptospiral toxins (hepatocellular necrosis);

  • Periportal inflammation and necrosis

  • Intracanalicular bile plugs —> jaundice

  • Intravascular haemolysis-> jaundice->centrolobular necrosis (hypoxia)

• Can develop to chronic active hepatitis

How does leptospirosis affect the kidneys in dogs?

Tubular necrosis (esp. L. grippotyphosa, L. canicola)

What is causing these lesions?

Leptospirosis

• mottled appearance due to haemorrhage and necrosis

• Jaundice

  • Due to intravascular haemolysis and/or bile stasis

    • Can also get anaemia cuasing centrolobular necrosis in liver 2° to ischaemia and hypoxia

• Gallbladder and bile ducts filled with blood

What are the histological features of leptospirosis?

• Hepatocellular dissociation (loss of tight junctions between hepatocytes)

  • Causes loss of pressure between cells which induces mitosis → Mitotic figures (arrows)

• Rounded cells

• Eosinophilic granular cytoplasm

• Dark shrunken basophilic nuclei

• Loss of cords/plates (dissociation)

• ^^^ Leptospira with Warthin Starry (silver stain) highlights bacteria

What aetiological agent causes Tyzzer's disease?

Clostridium piliforme

• [ZOONOSIS]

• [motile, spore-forming, gram-negative, obligate intracellular, commensal in gastrointestinal tract of small rodents —> faecal contam]

What animals does Tyzzer's disease affect?

• laboratory rodents, guinea pigs, foals, dogs, cats

• young or immunocompromised animals

What is the pathogenesis of Tyzzer's disease?

• contact with rodent (prey) faeces

• prolif in intestinal epithelial cells (ulcerative, necrotising colitis and typhlitis) with immunosuppression (?)

• spread to liver

• necrosis

• foals —> infectious route not known

What has caused these lesions?

Tyzzer's diseass

What protozoan infections cause parasitic hepatitis? What are their features

• Toxoplasmosis (toxoplasma gondii, zoonosis)

  • Can see tachyzoites in hepatocytes

    

• Leishmaniasis

  • Biting inseccts → generalised, chronic infection

  • Infection of macros → replication → rupture of cells → release

  • Typically chronic infection

  • Granulomatous hepatitis

  • Amastigotes in macrophages

    

What coccidiosis can affect the liver?

Eimeria stiedai in hares and rabbits

What are the features of Eimeria stiedai?

• replication in bile duct epithelium —> induction of

• proliferation of bile duct epithelium

• proliferation (sporo- and gammogonia in bile duct epithelium) and induction of papillary proliferation of bile duct epithelium

• Chronic hyperplastic cholangitis

What metazoan infections can cause parasitic hepatitis?

• Trematodes

  • Liver flukes —> Fasciola hepatica, Dicrocoelium dendriticum

• Cestodes - hydatid cysts

  • Echinococcus granulosus

  • Echinococcus multiocularis

  • Cysticercus tenuicollis

  • Taenia hydatigena

• Nematodes

What are the two forms of Fascioliasis?

• Acute fascioliasis —> due to larval migration

• Chronic fascioliasis —> due to mature fluke in bile ducts

How does acute fascioliasis present grossly and histologically?

• haemorrhage & necrosis with eosinophils and granulomatousinflammation

  • Acute but granulomatous inflam

What are the possible consequences adn outcomes of acute fascioliasis?

Consequences:

hepatic dysfunction, anaemia

Outcome:

1) healing —> granulations tissue → residual scarring → diffuse fibrosis

2) Black disease (Clostridium novyi) —> spores latent in macrophages (liver), & proliferate in anaerobic (necrotic) areas

3) chronic fascioliasis

What lesions does chronic fascioliasis cause?

• chronic hyperplastic cholangitis

• peribiliary fibrosis +/- calcification due to mechanical irritation, bile stasis, excretions

  • 'Pipe stem appearance'

    

What are the possible consequences of chronic fasciolosis?

• anaemia

• hypoproteinaemia

• chronic debilitation

• death (sheep)

What are these lesions assocaited with?

Cestodes —> “hepatophilic”

What are these lesions assocaited with?

Cestodes —> “serosophilic”

What is this lesion associated with?

• 'Milk spot liver' —> fibrosis & hepatitis due to migration through liver parenchyma + eosinophil-dom inflam

• Ascaris suum (pig) (also toxocara canis, and t. mystax)

  • Multifocal interstitial hepatitis

  • Chronic eosinophil dominated periportal infiltration