Lesson 99 - Circulatory and Infiltrative Disorders of the Liver

What type of disorder is passive congestion?

circulatory disorder

What type of disorder is congenital portosystemic shunt?

circulatory disorder

What type of disorder is congenital portal vein hypoplasia?

circulatory disorder

What type of disorder is portal hypertension with acquired vascular shunt?

circulatory disorder

What type of disorder is telangiectasis?

circulatory disorder

What is passive congestion?

reduced hepatic outflow due to cardiac dysfunction

What causes passive congestion?

right-sided heart failure which produces elevated pressure in the caudal vena cava that extends to the hepatic vein

What does high pressure in hepatic vein during passive congestion cause in the liver?

centrilobular congestion of sinusoids

What are common causes of right-sided heart failure resulting in hepatic congestion?

Dirofilarial immitis, valvular endocardiosis of the tricuspid valve in old dogs

What does hypoxia with passive congestion result in?

centrilobular degeneration, atrophy, loss of hepatocytes

What does chronic hypoxic injury in passive congestion lead to?

steatosis (fatty degeneration)

What pattern can we see with passive congestion?

enhanced lobular pattern (nutmeg liver)

What are the gross lesions of passive congestion?

lobes of liver are enlarged with rounded edges

What is congenital portosystemic shunt?

abnormal vascular structure that allows portal blood to bypass the liver and drain directly into the systemic circulation

How does congenital portosystemic shunt affect the animal?

stunts growth

What are frequent signs of congenital portosystemic shunt?

hepatic encephalopathy signs like ataxia, seizure, blindness, head pressing

Why does congenital portosystemic shunt cause hepatic encephalopathy?

due to hyperammonemia

What can seen histologically with congenital portosystemic shunts?

lobular atrophy, portal miniaturization, small or absent portal veins, reduplication of arterioles

What do you see grossly with congenital portosystemic shunts?

microhepatica

What are the types of portal systemic shunts?

intrahepatic shunts and extrahepatic shunts

What animals more commonly have intrahepatic shunts?

large breed dogs

What causes intrahepatic shunt?

due to failure of closure of the ductus venosus

What are the extrehepatic shunts that can occue?

portal vein to caudal vena cava anastamosis, portal vein to azygos vein anastamosis

What animals more commonly have extrahepatic shunts?

small breed dogs and cats

What happens with portosystemic shunt patients with their bladder?

ammonium biurate crystalluria due to abnormal ammonium metabolism

What is congenital portal vein hypoplasia also referred to as?

hepatic microvascular dysplasia

What animals have congenital portal vein hypoplasia?

dogs and occassionally cats

What breeds have a suspected inheritance of congenital portal vein hypoplasia?

yorkshire terriers, maltese, cairn terriers, tibetan spaniels, shih-tzus, havanese

What is congenital portal vein hypoplasia characterized by?

abnormally small portal veins

What does congenital portal vein hypoplasia result in?

diminished hepatic perfusion and portal hypertension

What do animals with congenital portal vein hypoplasia also have?

microhepatica and ascites

How do you differentiate between congenital portal vein hypoplasia and portosystemic shunts?

radiology

What are the causes of portal hypertension?

thrombosis or other types of occlusions and intrahepatic causes

What are some intrahepatic causes of portal hypertension?

fibrosis, nodular regeneration, lobular remodeling, veno-occlusive disease, microvascular dysplasia, sinusoidal amyloidosis

What can persistent portal hypertension lead to?

ascites and development of acquired portosystemic shunts

What are things that can be hepatocellular infiltrations?

amyloid, copper, iron, bile pigments, lysosomal storage diseases, glycogen, lipid

What are the main mechanisms of abnormal intracellular accumulations?

inadequate removal and degradation, excessive production of an endogenous substance, deposition of an abnormal exogenous material

What are the pathways in abnormal cellular infiltrations?

defect in metabolism, defect in protein folding or transport, lack of an enzyme to degrade a substrate

What can result from defect in metabolism?

hepatic lipidosis

What can result from defect in protein folding?

amyloidosis

What can result from lack of an enzyme resulting in failure to degrade a substrate?

storage diseases

What type of disorder is amyloidosis?

hepatocellular infiltration disorders

What type of disorder is canine copper-associated hepatopathy?

hepatocellular infiltration disorders

What type of disorder is hemochromatosis?

hepatocellular infiltration disorders

What type of disorder is canine degenerative vacuolar hepatopathy?

hepatocellular infiltration disorders

What type of disorder is hepatic lipidosis?

hepatocellular infiltration disorders

What is amyloidosis?

extracellular deposition of abnormal proteinaceous substance in tissues; protein misfolding disorder

What are the forms of amyloidosis?

amyloid light chain protein and amyloid associated protein

What is amyloid light chain protein?

derived from abnormal plasma cells secreting light chain fragments into circulation

What is amyloid associated protein?

secreted by liver in response to cytokines

What is secondary amyloidosis commonly a result of?

prolonged systemic inflammation

What animals have inherited amyloidosis been reported in?

shar-pei dogs, abyssinian cats, siamese cats

What are the gross lesions of amyloidosis?

livers are enlarged with rounded edges, friable, and pale

What can severe cases of amyloidosis cause?

hepatic failure, liver susceptible to fracture and hemorrhage

What is seen histologically with amyloidosis?

amyloid deposition within the space of disse, portal tracts, within and around blood vessels

Where does amyloid deposition start?

space of disse then extends to sinusoids

What is the stain used for amyloid?

congo red

What does accumulation of copper lead to?

reactive oxygen species causing oxidative injury to mitochondria

What lesions can be seen with copper accumulation?

centrilobular necrosis, inflammation, fibrosis, nodular remodeling, eventually cirrhosis

What dogs have been reported to have disorder of copper metabolism?

labrador retriever and bedlington terriers

What does copper accumulation cause?

canine copper-associated hepatopathy

What is a common cause of chronic hepatitis?

canine copper-associated hepatopathy

Why do bedlington terriers have copper metabolism issues?

mutation in COMMD1 gene

Where does copper accumulate?

centrilobular regions and within kupffer cells

What animals other than dogs have issues with copper accumulation?

sheep

Why do sheep have issues with copper?

poorly regulated copper storage and more susceptible to copper toxicosis

What exacerbates copper toxicosis in sheep?

low dietary molybdenum and sulfur

What precedes the chronic copper accumulation in the liver in sheep?

rapid release of copper into blood

What can trigger the release of copper in sheep?

stress or illness

What does hepatocellular copper accumulation diagonisis require?

liver biopsy

What stain is used with copper?

rhodanine special stain

What is another term for iron storage disease?

hemochromatosis

What is iron storage disease?

abnormally increased amount of iron storage within the liver

What organisms inherit iron storage disease?

people, Mynah birds, toucans, Salers cattle, horses

What in pet birds can lead to hemochromatosis?

excessive intake of dietary iron

What tends to accumulate in the liver during cholestatic disease?

bile

What stain is used for iron?

prussian blue reaction

What is a large group of rare inherited metabolic disorders that result from defects in lysosomal function?

lysosomal storage diseases

What type of genetic disorder is lysosomal storage disease?

autosomal recessive disorder

What is the result of lysosomal storage diseases?

cytoplasmic swelling and vacuolization of hepatocytes, macrophages, neurons, and other cell types

What kind of animals have lysosomal storage diseases?

young animals

What is canine degenerative vacuolar hepatopathy?

glycogen type VH

What is canine degenerative vacuolar hepatopathy associated with?

stress, cushings disease, genetic storage disease, glucocorticoid administration

What is lipid type VH associated with?

hypoxia, toxins, hypothyroidism, diabetes mellitus

How do you resolve canine degenerative vacuolar hepatopathy?

treatment of underlying disease

What tests are used to diagnose canine degenerative vacuolar hepatopathy?

liver biopsy, increase in serum ALP and mildly elevated ALT

Why is ALP elevated in canine degenerative vacuolar hepatopathy?

severe swelling of hepatocytes which can lead to blockage of bile canaliculi and intrahepatic cholestasis

What is grossly seen with hepatocellular glycogen accumulation?

liver is enlarged, pale, with enhanced lobules

What animals have bovine fatty liver disease?

dairy cows in late gestation or peak lactation, especially after any period of inappetance or anorexia

What ponies, miniature horses, and donkeys get hepatic lipidosis?

overweight, pregnant, or lactating mares after a period of stress or anorexia