Liver and biliary system pathology 2

What type of necrosis is usually seen in the liver?

Coagulative —> intact but dead hepatocytes → cells shrunken, intensely eosinophilic w/ altered nuceli

What are the different types of coagulative necrosis?

• Multifocal

• Zonal

• Massive / diffuse

Describe multifocal necrosis

• Aggregates of necrotic hepatocytes —> random i.e. no pattern within lobules

• With disseminated infections

What are the different types of zonal necrosis?

• In particular part of lobule / acinus

• Centrolobular / periacinar necrosis

• Mid-zonal necrosis (rare)

• Periportal/ biliary necrosis

  

What is being shown here?

Multifocal coagulative necrosis - two foci that have lost cellular outline + nuclar debris

Caused by Tyzzer’s dx —> Clostidium piliforme

What is being shown here?

Haemorrhagic dx in rabbit caused by calicivirus —> focal coagulative necrosis:

• Hypereosinophilic cytoplasm, shrunken nuclei

What is being shown here?

Disseminated multiocal necrosis

Small pale tan spots are the necrotic foci (surrounded by red rings = haemorrage / necrosis)

Why is centrobular / periacinar necrosis most frequent?

• Hepatocytes most at tisk of hypoxia

• Metabolically active (cytochrome P450)

When would peri-portal necrosis occur?

• Unusual e.g. phosphorus poisoning

• Biliary inflammation

• Portal circulation

When would massive (diffuse) necrosis occur?

Necrosis of entire lobe(s)

• With extensive zonal necrosis

• Circulatory disorder (infarction)

• Pigs with vitamin E / selenium deficiency (Hepatosis dietetica)

• Torsion of the lobes

Describe hepatosis dietetica in pigs

Associated oedema of gall bladder wall & Mulberry Heart Dx (multifocal myocardial haemorrhage & myofibre degen)

What are the different options for resolution after necrosis?

• regeneration of hepatocytes

• replacement of parenchyma by fibrous scar (due to destruction of reticular framework)

(if not resolution, removal of dead hepatocytes)

What are the different areas that fibrosis can occur?

At the site of necrosis, pattern depends on distribution of injury

• periportal / biliary fibrosis

• centrolobular / periacinar fibrosis

• diffuse / bridging fibrosis (areas of fibrosis might join up after massive necrosis)

  

What is being shown here?

• Extensive fibrosis between hepatic cords (dissecting fibrosis)

  • collagen extends out along sinusoids, growth between hepatocytes → interferes with blood flow i.e. passage of nutrients, metabolites etc.

• Often leads to further degeneration and necrosis of hepatocytes

What is hepatic cirrhosis?

End stage liver dx (irreversible) due to several causes

what are the characteristic features of hepatic cirrhosis?

• DEGENERATION —> disruption of entire liver architecture

• REGENERATION —> regenerative nodules of hepatocytes (loss of lobular structure so unable to carry out function)

• REPAIR —> bridging fibrosis [central pathogenic process]

What are the features of the regenerative nodules in liver cirrhosis?

• composed of hepatocytes

• lack of lobular organisation [no cords, no central vein, no triad]

• often hydropic degeneration of hepatocytes

• surrounded by fibrous connective tissue

What further attempts of regeneration can be made with Hepatic cirrhosis?

Bile duct proliferation

What is being shown here?

regenerative nodule, which is surrounded by fibrosis and contains hepatocytes which lack sinusoidal organisation (no sinusoids in between hepatocytes)

What are further characteristics of hepatic cirrhosis?

• parenchymal injury and fibrosis are diffuse (i.e. throughout the whole organ)

• balance between regeneration and constrictive scarring ® nodularity

• reorganisation of vascular structure [intrahepatic anastomoses]

• central pathogenic process —> progressive fibrosis

What is being shown here?

• Large number of small nodular lesions, which are the regenerative nodules

• Tissue between these is pale tan and depressed from the surface in comparison

• End stage —> cannot improve

What is being shown here?

• Liver cirrhosis

• Multiple regenerative nodules of varying size, surrounded by fibrosis —> stained blue

• Very little functional parenchyma left

What is being shown here?

Extensive fibrosis in hepatic cirrhosis

Regenerative nodules larger in size

What is being shown here?

• Cut surface of a cirrhotic liver

• Pale tan to yellow bridging areas are collagen or fibrosis, & the dark tan areas = remaining hepatic parenchyma.

  • bridging fibrosis seen

What is thought to cause Hepatic cirrhosis in dogs & other species?

• Majority of cases idiopathic

• Dogs = persistent CAV-1 or leptospira infection

What are the rare things that could cause cirrhosis?

• Parasitic (ascaris spp. & liver flukes)

• Cardiac (chronic passive congesion due to CHF)

• Post-necrotic (toxins, infectious agents)

• Pigment (with haemochromatosis)

• Biliary (due to chronic cholangitis in cats)

• Toxic

What can occur secondary to hepatic cirrhosis?

• Jaundice (icterus) due to impaired hepatic function

  • always diffuse because in systemic circulation

• Ascites due to portal hypertension

• Hepatoencephalic syndrome —> failure of liver to remove ammonia from blood → CNS signs

What is being shown here?

Severe jaundice due to leptospirosis

What is being shown here and what is it due to?

• Jaundice

• High bilirubin levels in the blood → yellow tinge of ALL tissues

  • seen only grossly

What are the different types of jaundice you can get?

• Pre-hepatic = excessive haemolysis

• Hepatic = severe hepatic injury

• Post-hepatic = obstructed bile flow

What are the components of bile?

Bile = yellow-green in colour

• water

• cholesterol

• bile salts (Na + K)

• bile pigments (bilirubin) from Hb molecule

  • globin + haem (haem = broken down into iron & biliverdin → bilirubin)

What are the features of pre-hepatic jaundice?

• Due to excessive haemolysis of erythrocytes in peripheral blood

  • Infections —> lepto, EIA, haemolytic streptococci, anthrax, snake venom

  • massive internal haemorrhage

  • incterus neonatorum (bilirubin glucoronyl transferase still insufficient)

• Unconjugated bilirubin in blood

What are the features of hepatic jaundice?

• Due to severe hepatic injury by toxic substances or infectious agents (e.g. lepto)

• Damaged hepatocytes do not uptake bilirubin or perform conjugation (unconjugated bilirubin)

• Severe hepatocyte swelling blocks outflow of bile from canaliculi (conjugated bilirubin)

What are the features of post-hepatic jaundice?

• Due to obstruction of normal bile flow

• Conjugated bilirubin accumulates in liver and is reabsorbed into the blood

What are the causes of Post-hepatic jaundice?

• see hepatic jaundice

• obstruction of ducts [e.g. liver fluke…]

• fibrous tissue in cirrhosis

• cholangitis

• gall stones

• pressure on ducts [abscesses, granulomas, neoplasms]

• closure of excretory duct [duodenal papilla]

What can sometimes be seen histologically with jaundice?

Accumulation of bile within canaliculi and bile ducts

What are the hepatic functions?

• Metabolism: Processes carbs, fats, and proteins

• Detoxification: Breaks down drugs and toxins (from int tract and other organs)

• Bile production: Aids fat digestion

• Storage: Stores glycogen, vitamins, and iron

• Synthesis: Makes proteins like albumin and clotting factors

• Immune function: Filters blood and supports immune response

What does hepatic failure lead to?

• Jaundice

• hypoalbuminaemia (reduced synthesis & secretion of albumin → ascities)

• Coagulopathy (reduced synthesis & secretion of clotting factors)

• Hyperammonaemia (reduced detoxification by conversion to urea & glutamine)

  • (albumin helps maintain osmotic pressure of circulation)

• Poral hypertension (→ ascites)

What does hyperammonaemia lead to?

• Hepatic encephalopathy

• Cerebral oedema (Status spongiosus)

• Neuronal necrosis and swelling

• Degeneration of astrocytes

What is being shown here?

• Alzheimer type II astrocytes (black arrows)

• Status spongiosus (cerebral oedema; arrowhead)

What is being shown here?

Liver —> portal triads lacking veins

What is being shown here?

Nodular hyperplasia

• not a neoplasm

• common in old dogs

• single or multiple

• compression of adjacent tissue (which looks normal)

• contain portal areas

Describe regenerative nodules

• Not neoplasm

• Multiple / numerous

• Adjacent tissue usually fibrotic

• Loss of lobular architecture

What is being shown here?

Hepatocellular adenoma

• usually single

• sharply delineated

• no portal areas / lobular structure

• compression of adjacent tissue

• may become quite large

• do not metastasise (benign)

  

What is being shown here?

Hepatocellular carcinoma

• compression & invasion of adjacent tissue, invasion of portal vessels

• poorly demarcated

• metastasis

What can cause Hepatocellular carcinoma?

• Aflatoxins

• Some viruses (hepatitis B in humans)

What is being shown here?

Bile duct adenoma (confined to one area)

• often cystic [cystadenoma]

• usually single

• sharply delineated —> surgical management poss

• compression of adjacent tissue

• may become quite large

What is being shown here?

Bile duct carcinoma

• commonly spreads along biliary tract

• metastasis [spread to hepatic serosa, via lymph nodes to lungs]

• often inducing desmoplasia (fibrosis in response to tumour → firm, nodular feel)

What is a Haemangiosarcoma?

• Malignant neoplasm arising from endothelial cells

• Liver can be primary site or site of metastases

Why is the liver a frequent site of metastases?

• portal vein [from pancreas and intestine]

• veins / arteries at sites of entry [any other neoplasms]

• contact metastases [serosa; from malignant tumours in abdominal cavity; less common]

What are the different presentations of metastasis in the liver?