L3: Liver Path

What are the main functions of the liver in domestic animals?

• Processing dietary carbohydrates, lipids, amino acids, and vitamins

• Maintaining metabolic balance (lipid and glucose turnover, synthesis, and storage)

• Synthesizing and turning over plasma proteins (e.g., clotting factors, albumin, vitamin K)

• Detoxifying and excreting endogenous wastes and xenobiotics via bile

• Providing innate immunity (Kupffer cell filtration, cytokine synthesis, Pit cells)

Describe the structure of the hepatic acinus and its functional zones.

• Zone 1 (Periportal): Closest to nutrient and oxygen-rich blood; main site for gluconeogenesis, protein synthesis, aerobic metabolism, urea, lipid, and cholesterol metabolism.

• Zone 2 (Midzonal): Transitional area.

• Zone 3 (Periacinar/Centrilobular): Furthest from blood inflow; main site for glycolysis, lipogenesis, and biotransformation (high cytochrome p450 activity).

What are the principal pathologic processes that can affect the liver?

• Developmental anomalies (e.g., cysts, biliary atresia, vascular anomalies)

• Traumatic lesions (displacement, torsion, rupture)

• Hepatocellular adaptations (hypertrophy, atrophy, polyploidy, multinucleation)

• Intracellular accumulations (pigments, glycogen, lipids, amyloid)

Name and describe two clinically important liver diseases in domestic species.

1. Ovine White Liver Disease:

   • Affects lambs and goats; caused by cobalt and vitamin B12 deficiency.

   • Clinical signs: ill-thrift, anorexia, mild anemia, photosensitization, icterus, hepatic encephalopathy.

   • Pathology: fatty liver, ceroid accumulation, bile duct proliferation.

2. Feline Hepatic Lipidosis (Fat Cat Syndrome):

   • Affects obese, nutritionally stressed female cats.

   • Clinical signs: vomiting, anorexia, weakness, jaundice, hepatomegaly.

   • Pathology: severe hepatic lipidosis, hyperbilirubinemia, increased ALP and GGT.

What are the main types of hepatocellular adaptations and their causes?

• Hypertrophy: Increased liver size due to increased functional demand (e.g., xenobiotic exposure).

• Atrophy: Decreased liver size due to reduced demand, illness, or starvation; involves apoptosis and autophagy.

• Polyploidy: Increased DNA content in hepatocytes, often due to age or toxins.

• Multinucleation: Increased binucleation in young or regenerating livers.

What are the main types of intracellular accumulations in hepatocytes?

• Pigments: Melanin (congenital/acquired), lipofuscin (wear and tear), ceroid (pathologic), haemosiderin (iron), bile, parasitic pigments.

• Glycogen: Excess glucocorticoids cause hepatic glycogenosis.

• Lipids: Hepatic lipidosis due to metabolic derangement, toxicity, or hypoxia.

• Amyloid: Overproduction of amyloid A due to chronic inflammation.

Which hepatocytes are most susceptible to direct-acting toxicants and why?

Zone 1 (Periportal) hepatocytes are most susceptible to direct-acting toxicants because they are closest to the incoming blood supply and thus exposed to the highest concentrations of toxins.

Which hepatocytes are most susceptible to hypoxia and metabolically activated toxicants?

Zone 3 (Periacinar/Centrilobular) hepatocytes are most susceptible to hypoxia and metabolically activated toxicants due to their location furthest from the oxygen-rich blood supply and higher cytochrome p450 activity.