Systemic Pathology: Liver

What are some functions of the liver?

• Metabolic: lipid, carbs, protein metabolism 

• Bile production and secretion

• Phagocytosis (Kupffer cells (special macrophages) in sinusoids remove bacteria, debris, and old RBC)

• Extramedullary Haematopoiesis 

• Detoxification

What are some clinical signs of liver disease?

1. Jaundice

2. Hepatogenous photosensitivity

3. Hepatic Encephalopathy (brain dysfunction)

4. Coagulopathies

5. Oedema and Ascites

6. Superficial necrolytic dermatitis (Hepatocutaneous syndrome)

What are some responses that can transpire if the liver is injured?

1. Regeneration- Micronodular (small uniform nodules from chronic toxic/ alcohol injury) and Macronodular (large irregular nodules from post-hepatitis/ necrosis)

2. Fibrosis- Scarring response to chronic liver damage
   - Patterns depend on the type of injury (billary, post-necrotic, diffuse, periacinar fibrosis)

3. Bile duct Hyperplasia- Proliferation of bile ducts due to injury or obstruction.
   - Cirrhosis- diffuse liver disease with fibrosis (scarring) and nodular regeneration (micro and macro nodules) that disrupts normal liver function.
   Leads to portal hypertension, impaired metabolism, reduced detoxification, and liver failure.

List some incidental lesions of the liver.

1. Tension lipidosis

2. Capsule Plaques or Fibrous Tags

3. Telangiectasis

4. Gallbladder Anomalies

A horse is presented with a wedge-shaped liver that is well demarcated with pale adipose tissue. State the condition, the reason behind it, and the type of lesion.

1. Tension lipidosis

2. Caused by pressure/ stretching of the liver capsule.

3. Incidental

A horse is presented with white fibrous strands/ plaques on the diaphragmatic surface of the liver capsule. State the possible condition and the reason for this phenomenon.

1. Capsule Plaques or Fibrous Tags

2. Caused by strongyle migration and is formed after mild perihepatitis or trauma.

What is the meaning of Telangiectasia in the liver?
State the common appearance, causes and species affected.

1. Localized dilation of liver sinusoids (cavernous ectasia)

2. Appearance: slightly sunken, dark red foci scattered in the liver

3. Caused by Bartonella infection in dogs, idiopathic, and linked to vascular fragility or congestion.

4. Species affected: older cats and cattle

What are some congenital and acquired anomalies occurring in the liver?

1. Cysts: fluid-filled cavities in the liver (present at birth or during life)

2. Congenital biliary cysts: cystic dilations of bile ducts 

What ways can the diaphragm cause issues with the liver?

1. Displacement caudally: diaphragm moves downward due to bloat, pregnancy, or diaphragmatic paralysis. 

2. Hernia: liver enters thoracic cavity through diaphragmatic defect (congenital or acquired from trauma)

What consequences can occur if a liver is twisted?
State which lobe and species are affected.

1. Consequences: venous outflow obstruction leads to congestion, infarction, shock, death. 

2. Left lateral lobe is affected in pigs and dogs.

What predisposing factors can weaken liver tissue?

1. Inflammation (hepatitis)

2. Fatty change (hepatic lipidosis)

3. Amyloidosis (friable liver) 

What animals are predisposed to melanosis in the liver?

Melanosis (black/dark patches) in calves, piglets, lambs

What are the types of lipopigments (yellow/brown granules in hepatocytes)?

1. Lipofuscin- age pigment

2. Ceroid- pathological pigment from auto-oxidation of polyunsaturated fats.

What are some causes of Haemosiderosis?

1. Iron overload (excess supplementation)

2. Haemolytic anaemias (increase RBC destruction)

3. Copper deficiency

4. Cachexia (chronic wasting)

What are amyloids?
State the location. 

1. Misfolded protein deposits secondary to chronic inflammation.

2. Deposited in the space of Disse (between hepatocytes and sinusoids)

What are some examples of reversible liver injury responses?

1. Cell swelling (Hydropic degeneration, cloudy swelling)

2. Fatty change (Hepatic lipidosis, steatosis) 

What issues can cause Cell swelling of the liver?

1. Hypoxia, toxins, drugs

2. Impaired Na/K+ ATPase → sodium and water accumulate in hepatocytes

3. Smooth ER activation (in response to toxins/drugs)

What are some physiological and pathological causes of fatty liver?

Physiological:

• Fasting (mobilization of fat stores)

• Pregnancy (ruminants)

• Early lactation (cows)
  
  Pathological:

• Genetic (Hyperlipidemia in horse and cat)
  

What are some metabolic disorders that can lead to Hepatic lipidosis?

1. Pregnancy toxaemia and ketosis in sheep and cattle

2. Diabetes mellitus

3. Hypothyroidism

4. Hyperadrenocorticism

What deficiencies can lead to Hepatic Lipidosis?

• Anaemia

• Choline deficiency

• Cobalt/ Vitamin B12 deficiency

What are some causes of atrophy (small liver with thin edges) in the liver?

1. Portosystemic shunts (blood bypass liver → reduce function)

2. Malnutrition

3. Portal streaming (unequal blood distribution in liver)

What are some causes of Hepatomegaly?

1. Chronic passive congestion (right side heart failure → nutmeg liver)

2. Cell swelling (hydropic degeneration)

3. Fatty change (lipidosis)

4. Amyloidosis

5. Diffuse inflammation (hepatitis)

6. Diffuse neoplasia (lymphoma, metastatic tumors)

State examples of irreversible patterns of liver necrosis.

1. Single cell necrosis

2. Focal necrosis

3. Centrilobular (periacinar) necrosis

4. Midzonal necrosis

5. Periportal necrosis

6. Paracentral necrosis

7. Massive/ Submassive necrosis

8. Pannecrosis

What are some causes of single cell necrosis of the liver?

• Viral infections, toxins, mild hypoxia

What are some causes of small and large focal necrosis in the liver?

• Small: EHV-1, Salmonella, T. gondii

• Large: F. necrophorum

What are some causes of centrilobular necrosis in the liver?

• Hypoxia, passive congestion (nutmeg liver), exogenous toxins metabolized by cytochrome P450

What causes midzonal necrosis in the liver?

• Phytotoxins, rodent toxicity

What causes periportal necrosis in the liver?

• Phosphorus poisoning, acute sporidesmin toxicity (facial eczema in ruminants)

What causes necrosis of entire lobules or large portions of the liver?

1. Serum hepatitis (Theiler’s disease in horse) → immune complex (T3 hypersensitivity) 

2. Blue-green algae in cattle

3. Cardiac failure in pigs

4. Acute iron toxicity in piglets

5. Parenteral copper toxicity in calves

6. Hepatosis dietetica in pigs (deficiency in VIT E → high polyunsaturated fats)

What are some causes of portal hypertension and state the possible consequence.

Causes: Hepatic necrosis, hepatic fibrosis, right side congestive heart failure, cardiac tamponade
Consequence: Ascites

What is the reason behind the term nutmeg liver?

• Caused by:

  • Chronic passive congestion (right-sided heart failure where venous blood cannot exit liver)

  • Caudal vena caval thrombosis

  • Liver incarceration in a diaphragmatic hernia

  • Chronic partial torsion of liver lobe

What can arise from Chronic passive congestion?

• Centrilobular necrosis and fibrosis

• Sinusoidal engorgement

• Periportal fatty change

• Ascites

What is the meaning of Portosystemic shunts and state the types. 

1. Abnormal connection between portal and systemic circulation that bypass the liver preventing detoxification. 

2. Types: Congenital (dogs and cats) and Acquired PSS
   

What findings are seen in congenital PSS?

• Affects small runts showing hepatic encephalopathy

• Contributes to high ammonia and bile acids, low urea and albumin and crystals in urine. 

What are the five main congenital types of PSS?

• Patent ductus venosus

• Portal vein atresia

• Portocaval

• Porto-azygos

• Portocaval-azygos

How does Acquired PSS occur?

• Develop secondary to portal hypertension.

What does cholelithiasis (gallstones) cause and the predisposing factors?

    Cause:

• Obstruction of bile flow → cholestasis 

• Icterus

• Cholecystitis (inflamed gallbladder)
  
  Predisposing factors: 

• Bile stasis

• Infection

• Altered bile composition

What are some gross lesions associated with EHV-1 and state the species affected.

• Necrotic foci of liver, spleen, lung

• Icterus

• Pulmonary congestion and edema
  
  Foals- aborted or weak neonates

What are some gross lesions associated with Canine Herpesvirus and state the species affected.

• Necrotic foci and haemorrhages in the liver, lungs, kidney, adrenals, spleen, brain, and intestines.

• Also contributes to cerebellar hypoplasia, retinal dysplasia, and renal dysplasia

• <2 weeks (fading puppy syndrome)

What are some lesions associated with Canine Hepatitis caused by CAV-1?

• Yellow-brown mottled liver with fibrin strands on surface. 

• Edema and hemorrhage of gallbladder

• Petechiae in brain

• Blue eye

What are some lesions associated with FIP?

• Multifocal to coalescing granulomas, organizing exudate on liver capsule,granulomatous inflammation around veins and bile ducts.

Suggest routes of spread for bacterial hepatitis.

• Haematogenous spread via portal vein (from GIT), hepatic artery or umbilical vein.

• Biliary tree

• Direct extension from hardware disease

Campylobacter fetus subsp fetus cause?

Abortion and neonatal disease in lambs with target shape necrotic foci on liver.

Mycobacterium cause?

Cause miliary granulomas in the liver; Johne’s disease (M. paratuberculosis) stained with acid fast (Ziehl- Neelsen)

Pasteurella multocida cause?

Abortion of lambs causing septicemia with liver involvement

What can liver abscess cause in cattle?

• Rupture into peritoneal cavity → peritonitis

• Rupture into hepatic veins or caudal vena cava → septic pulmonary emboli (PEA)

What lesions does F. necrophorum cause and state what targeted species harbors this bacteria.

1. Cause large, multiple, coalescing necrotic foci in the liver.

2. Occur in navel-ill (omphalophlebitis) in neonatal lambs and calves leading to liver necrosis, pneumonia, septic arthritis (joint-ill), eye involvement, meningitis/ encephalitis.

Outline the pathogenesis of Navel-Ill.

1. Entry via umbilicus from dirty environment

2. Spread to bloodstream

3. Systemic localization (Joints, liver, lungs, kidneys (white spotted kidney), intestines, brain, eye and heart lining.

Black disease (Infectious necrotic hepatitis) is caused by?

Clostridium novyi in sheep, cattle, occasionally in horse and pigs from fluke migration (F. hepatica) and trauma.

Bacillary Haemoglobinuria is caused by?

Clostridium haemolyticum in cattle from fluke migration.

Tyzzer’s Disease is caused by?

Clostridium pilliforme in foals (1-5 weeks) with multifocal necrotic hepatitis, and is stained with Warthin-Starry

What does Ascaris suum (pig roundworm) cause?

Migrate to liver causing small white fibrotic foci (milk spot liver) 

What does F. hepatica cause in ruminants?

Chronic cholangitis, fibrosis, pipe-stem liver

Chronic active hepatitis (inflammatory disease progressing to necrosis and fibrosis) is common in what species?

Dogs and is caused by Canine adenovirus, Leptospira infection, Copper toxicosis (Hereditary in terriers, dobermanns) and Drug-induced (Anticonvulsants) that leads to chronic liver injury

Theiler’s disease (Serum hepatitis) is found in what species?

Horses thats iatrogenic from equine serum products (tetanus) that cause centrilobular to submassive hepatic necrosis that presents signs of icterus, hepatic encephalopathy, sudden death. 

Cholangiohepatitis in often seen in what species and is associated with what liver disease?

Mature cats with icterus 

What factors make the liver susceptible to damage from toxic substances?

1. Biotransformation role: The liver metabolizes harmful substances (xenobiotics) but can create free radicals that damage liver cells.

2. Natural Affinity/ Storage: The liver stores copper that build up.

3. Not metabolized at all: Phosphorus in liver.

Facial Eczema (Sporidesmiotoxicosis) is caused by?

Pithomyces chartarum spores → mycotoxin sporidesmin that causes icterus and hepatogenous photosensitivity.

Lesions:

• Acute: atrophy, capsular fibrosis

• Chronic: fibrosis, bile duct hyperplasia

What are some causes of Hepatogenous photosensitivity?

• Panicum

• Phomopsis

• Cestrum

• Blue-green algae cause massive necrosis

• Myoporum contain furano sesquiterpenes oils causing zonal necrosis.

What type of lesions does Ragwort (Senecio) poisoning inflict?

• Fibrosis, Nodular hyperplasia, and Megalocytosis (huge hepatocytes) of bovine liver

What clinical signs are present in copper poisoning?

• Chronic storage: hepatocellular necrosis → copper release → acute hemolysis

• Khaki colored icterus, gun-metal grey/ black kidney (due to hemoglobinuria from hemolysis)

Outline the sequence of events and species affected by cirrhosis.

• End stage liver disease: fibrosis + nodular regeneration + architectural distortion.

• Dogs: Barbiturate exposure, Aflatoxin, Copper toxicity, ICH. 

• Ruminants: Pyrrolizidine alkaloid toxicity, aflatoxin exposure