DMN (Lesson 86): Response to injury and common disorders of the liver

Portal tracts

reside peripherally at the angles of the hexagon and contain three structures: 1) bile duct, 2) portal vein, 3) hepatic artery

Hepatic plates

one-cell-thick layers of hepatocytes that extend radially from the central vein and are separated by blood-filled hepatic sinusoids which have discontinuous endothelial cells

Patterns of hepatocellular necrosis: Random or embolic pattern

Multifocal areas of necrosis scattered randomly throughout the liver

Indicates a hematogenous route of entry (septicemia)

Typical of many blood-borne infectious agents including, viruses, bacteria, and protozoa

Image of Random hepatic necrosis. Multiple pale, yellow, foci of necrosis (Sawdust liver), cow. Cause: bacteria

Patterns of hepatocellular necrosis: Zonal

Specific areas of necrosis that are restricted to a particular portion of the hepatic lobule

Occurs with various specific types of liver damage such as hypoxic injury and hepatotoxicities

Centrilobular hepatic degeneration and necrosis

Occurs with hypoxic injury because Zone 3 receives the least oxygenated blood

Also occurs with hepatotoxicity that requires mixed function oxidases which are present in Zone 3

Mixed function oxidases function in the metabolism of drugs and toxins

Cytochrome P450 enzymes function in the liver?

convert drugs or chemicals into toxic metabolites

Centrilobular necrosis: Circumferential zone of hepatocellular necrosis around the central vein(Zone 3-arrow)

Midzonal necrosis

Sometimes reported in pigs and horses with aflatoxicosis

Periportal necrosis

Occurs following exposure to toxins such as phosphorus

General considerations of the liver

liver has a considerable functional reserve and good regenerative capacity(quickly in a matter of days to weeks)

Approximately 75% of the hepatic parenchyma can be removed without significant impairment of function: Clinical signs of hepatic failure are not expressed until functional reserve is lost

Consequences of hepatic failure

❖ Icterus (hyperbilirubinemia )

❖ Hepatic encephalopathy ( due to hyperammonemia)

❖ Vascular and hemodynamic alterations (e.g acquired portosystemic shunts)

❖ Cutaneous manifestations (hepatocutaneous syndrome and photosensitization)

❖ Immunologic manifestations due to reduced Kupffer cell function

❖ Coagulopathy resulting in bleeding tendencies

❖ Ascites secondary to hypoalbuminemia and/or portal hypertension

❖ Hypoglycemia

Consequences of hepatic failure: Icterus (hyperbilirubinemia)

Increased concentrations of conjugated or unconjugated bilirubin in blood

Yellow discoloration of tissues

More evident in visible mucus membranes, sclera, blood vessels

Hepatocellular regeneration: Regeneration after hepatic injury

Occurs rapidly if some hepatocytes survive in a lobule and the lobular stroma persists

Necrotic foci are quickly replaced by cellular division of adjacent hepatocytes

However, if whole lobules are destroyed, healing is by scarring

Hepatic fibrosis = an increase in the amount of collagen within the liver.

Occurs as a response to chronic injury and repeated injury.

Stellate cells within the space of Disse produce collagen

• Disrupts the exchange between hepatocytes and plasma → diminished hepatic synthetic, catabolic, and excretory functions

Biliary hyperplasia

Proliferation of newly formed biliary ducts within the portal tracts and periportal regions

Predominantly occurs with diseases that cause biliary inflammation, obstruction, and cholestasis

Biliary hyperplasia indicates long-standing (chronic) hepatic injury

End stage liver(cirrhosis)

Repeated injury and regeneration cycles promote the formation of fibrosis and nodular regeneration.

Diffuse process in the liver characterized by severe fibrosis and replacement of normal hepatic lobules with nodular regeneration and abnormal vasculature

pathogenesis of end stage liver(cirrhosis)

Chronic hepatotoxicity

Chronic hepatitis and/or cholangiohepatitis

Chronic biliary obstructive disease

Chronic degenerative liver disease

Acute hepatitis

Characterized by inflammation, hepatocellular necrosis, and apoptosis

Results in an embolic pattern which is randomly multifocal

Can result in death from acute liver failure if severe.

Cause of acute hepatitis

Occurs with systemic infections

• Viruses (herpesvirus)

• Bacteria (Clostridium piliforme, lepto)

• Fungi (blastomycosis, histoplasmosis)

• Protozoan (Toxoplasma gondii, Neospora caninum)

Chronic hepatitis

Characterized by fibrosis, mononuclear inflammatory cells, hepatocellular loss, nodular regeneration, and structural remodeling of the hepatic lobule and vasculature

Progressive loss of function may lead to hepatic failure and end-stage liver

Chronic hepatitis occurs with any chronic persistent antigenic stimulus

Chronic infections

Immune mediated disease

Metabolic disease

Long-term exposure to toxins or drugs

Nonspecific Reactive Hepatitis

Diffuse process in the liver that is a response to systemic inflammation

Most commonly stemming from gastrointestinal disease

Characterized by mild mononuclear inflammatory infiltrates in the portal tracts, less commonly around central veins

Cholangitis

Inflammation of the biliary ducts; may be either intrahepatic or extrahepatic

Chronic cholangitis may lead to cholestasis and icterus (hyperbilirubinemia )

Neutrophilic cholangitis (infectious): acute or chronic

Caused by ascending bacterial infection

Rupture of an infected intrahepatic bile duct may lead to hepatic abscess

Bacterial culture most often reveals: E. coli, Enterococcus, Bacteroides, Streptococcus, or Clostridium

Lymphocytic cholangitis (immune mediated)

A chronic, immune-mediated biliary disease of cat

Cholangiohepatitis

Inflammation of the biliary ducts and extension of inflammation into the surrounding liver parenchyma

Cause of cholangiohepatitis

Caused by an extension of bacterial cholangitis into the surrounding periportal hepatic parenchyma → more severe disease

Causes greater elevation of serum ALT due to damage of more hepatocytes

Liver neoplasia can arise from

Hepatocytes, Bile duct epithelial cells

Mesenchymal elements (e.g connective tissue and blood vessels)

Metastatic (neoplasm from another organ)

hepatocellular adenoma: Benign neoplasm of hepatocytes

Commonly described in young ruminants

Usually single, variably sized, brown masses

Compress adjacent parenchyma

Hepatocellular carcinoma: Malignant neoplasms of hepatocytes

Not common in all domestic species → Reported in dogs and ruminants, especially sheep

Described as massive(single mass), nodular and diffuse

Most common presentation of hepatocellular carcinoma

Solitary well demarcated mass involving entire lobe

Cholangiocellular adenoma: single, firm, discrete, white mass

Mass comprises tubules with well differentiated cuboidal epithelium separated by minimal stroma

Most common in cats

Cholangiocellular carcinoma

Common in all species

Large single mass or multiple masses

Gray-tan unencapsulated masses → Often metastatic to other tissues

Fatty liver: hepatocellular lipid accumulation

Within hepatocytes, free fatty acids are esterified to triglycerides, or converted to cholesterol or phospholipids

Triglycerides can be complexed with apoproteins to form low-density lipoproteins which are released into the plasma as an energy source

Lipidosis occurs when hepatocyte triglyceride accumulation exceeds the rate of lipoprotein release