Flashcards in Special Path - Liver Disease (viral, bacterial, toxins, etc.) Deck (66):
Infectious canine hepatitis virus
Centrilobular hepatic necrosis (may reflect ischemia) and random foci of necrosis (viral replication) and multifocal hemorrhage in other organs (tropism for endothelial cells)
Herpesvirus infections in nerborn or fetus (canine, equine, bovine)
Multifocal random foci of necrosis in variety of organs including liver
Feline infectious peritonitis virus may involve liver as manifestation of _____
Three routes bacteria can reach liver:
Blood, bile ducts, extension
Bacterial infections can cause formation of abscesses. This is common in cattle secondary to ____.
How do abscesses form in cattle secondary to ruminitis in bacterial infection? How do they cause death? What is the most common bacteria?
Damage to ruminal mucosa allows bacteria (particularly Fusobacterium necrophorum) to enter portal circulation and produce focal areas of necrosis and hepatitis that develop in hepatic abscesses. If abscess encroaches on vena cava, it may result in thrombosis and passive congestion of liver, or thromboemboli in lungs. Rupture of abscess into vena cava can cause death.
What route do bacteria enter the liver when causing multifocal hepatic necrosis or multifocal necrotizing hepatitis?
Examples of bacteria that enter liver via hematogenous route, causing multifocal hepatic necrosis or multifocal necrotizing hepatitis
(1) Clostridium piliformis in foals
(2) Salmonella in many species (can enter via bile ducts)
(3) Trueperella pyogens in bovine fetus and newborn
(4) Campylobacter fetus in fetal and newborn sheep
(5) Francisella tularensis in number of animals
How can salmonella enter the liver besides hematogenous route?
Liver involved in acute infection with Leptospira - ischemia to ____ areas, secondary to _____, and ____ necrosis of hepatocytes due to the presence of the organisms.
Ischemia to centrilobular areas secondary to hemolytic anemia and multifocal necrosis of hepatocytes due to presence of the organisms
Three species involved with Leptospira that involves liver?
Calves, lambs and pigs
Example of fungal disease that causes hepatitis?
Parasitic diseases - nematode migration through the liver is common but usually not significant. what lesions form?
Necrosis, inflammation, and fibrosis in localized areas
Name a nematode that migrates through the liver in swine
What happens when cattle are infected with trematodes (liver flukes)? Sheep?
Flukes encyst in cattle and can cause chronic lesions but do not usually cause death. In sheep, the flukes can cause extensive liver damage and death.
Canine chronic hepatitis - Chronic "active" hepatitis
This is a progressive liver disease that features hepatocellular necrosis associated with infiltration of mononuclear cells and fibrosis.
Chronic "active" hepatitis is a relatively common disease entity among dogs, especially this breed.
Advanced cases of chronic "active" hepatitis may have a _____ liver.
coarsely nodular (end-stage or cirrhotic)
Signs of chronic "active" hepatitis in dogs?
May see increase in liver enzymes, hypoalbuminemia, ascities, and coarsely nodular (cirrhotic) liver in advanced cases
Chronic lymphocytic cholangitis occurs in cats older than ___ years of age.
Chronic lymphocytic cholangitis is characterized by:
(1) Cats older than 4
(3) intrahepatic cholestasis
(4) Inflammation (lymphocytes and plasma cells) in portal areas around small bile ducts
(5) Bile duct proliferation
(6) Portal fibrosis
Cause of chronic lymphocytic cholangitis:
Unknown (may have an immunologic basis)
How can chronic lymphocytic cholangitis be differentiated from ascending infection of the biliary system?
Absence of neutrophils in chronic lymphocytic cholangitis
What are the two principal mechanisms of toxic liver disease?
(1) direct toxicity
(2) conversion of a xenobiotic to a toxin
What function does the liver have in relation to xenobiotics (exogenous chemicals)?
Central role in detoxification and excretion of xenobiotics, but liver may undergo severe necrosis when exposed to them.
process of liver to metabolize/detoxify and eliminate xenobiotics
process of liver generating toxic intermediate metabolites (often free radicals)
Why may the liver undergo severe necrosis when exposed to xenobiotics?
Because of bioactivation - formation of free radicals - that are more damaging than the parent compound (xenobiotic)
Free radicals can react with?
DNA, RNA, and cell membranes and proteins, as well as produce oxidative stress within hepatocytes
What determines the site where a compound undergoes bioactivation?
the distribution of drug metabolizing enzymes within the hepatic lobule
What zone is the most common to injury via bioactivation? Why?
Centrilobular (zone III) since there is a relatively high concentration of mixed function oxidases (cytochrome P-450 system) responsible for biotransformation in zone III of the hepatic acinus.
Cytochrome P-450 system
Resides in the smooth ER of hepatocytes and is the major enzyme system of the liver for drug metabolism.
Compounds that are hepatotoxic tend to be fat soluble as the microsomal enymes convert lipophilic substances to water soluble substances for clearance.
What zone of the liver is cytochrome P-450 system concentrated in?
Zone III - centrilobular
Compounds that are hepatotoxic tend to be ___ soluble.
Morphology of toxin induced hepatic injury varies considerable with:
type, dose, and duration of exposure to the toxin as well as other factors (species, age, sex, diet, hormonal status, genetic constitution, etc.)
Acute toxic injury is characterized by: (4)
(1) Cellular swelling
(2) Fatty degeneration
(3) +/- cholestasis
(4) +/- necrosis
Chronic toxic injury is characterized by: (3)
(2) Biliary hyperplasia
(3) Hepatocellular regeneration
Which anticonvulsant drugs may cause chronic hepatic disease and cirrhosis in dogs? (3)
Phenobarbital, phenytoin, and primidone
Phenobarbital stimulates ____ of the SER in hepatocytes by:
hyperplasia - increases activity of the microsomal enzyme system
What species are uniquely susceptible to acetominophen toxicity since they are less efficient in converting acetominophen into non-toxic intermediates?
Giving acetominophen to cats can lead to ____ damage in hepatocytes and cause ____
lead to oxidative damage in hepatocytes and cause hepatic necorisis
Which non-steroidal anti-inflammatory drug causes idiosyncratic hepatic disease in dogs?
NSAIDs - Carpofen
Exogenous and endogenous glucocorticoids increase hepatic storage of glycogen by inducing _____ activity.
With glucocorticoids in dogs, typical findings in glycogen accumulation are: (3)
vacuolated hepatocytes; hepatomegaly; and an increase in serum alkaline phosphatase activity
Is glyocgen accumulation reversible?
Yes, after withdrawal of exogenous steroids or correction of spontaneous hyperadrenocorticalism.
Drug toxicity is of principal concern in ____ animals.
Plant toxicity is of principal concern in ____ animals.
Pyrrolizidine alkaloids are found in:
Found in many plants - senecio, crotalaria, amskinkia
What happens to pyrrolizidine alkaloids in the liver?
Alkaloids must be metabolized to the active form, an ester, in the hepatic P-450 system
Esters are ____ agents that react with cytoplasmic and nuclear constituents in hepatocytes.
Which species of animals are most susceptible to pyrrolizidine alkaloids (plant toxicity)? Which are least affected?
Swine are most susceptible, followed by cattle, and horses, with sheep being least affected
Typical microscopic lesions caused by toxic plants (pyrrolizidine alkaloids for example)
Enlarged hepatocytes (megalocytes); fibrosis; bile duct hyperplasia; chronic intoxication can lead to cirrhosis and liver failure
Mycotoxins are ____ of fungi.
Aflatoxins are produced by _____ during storage feed (corn, peanuts, cotton seed) and converted to toxic _____ in SER hepatocytes.
Aflatoxins are produced by Asperigillus flavus; converted to toxic intermediate in SER hepatocyte
What animals are sensitive to mycotoxins?
Pigs, dogs, horses, and cattle
Acute toxication of mycotoxins is rare except in ____
Acute toxication of mycotoxins in dogs causes:
Hemorrhage, centrilobular to massive hepatic necrosis, lipidosis, and biliary proliferation
Blue-green Algae blooms usually occur during what seasons?
Late summer and early fall
How are blue-green algae toxic?
The algae contain preformed toxins that when ingested cause zonal or massive hepatic necrosis.
Consequences of excess accumulation of copper in lysosomes in liver are ____ dependent.
Species - dependent
Copper toxicity in sheep
Copper accumulates in the liver over a period of time (dietary excess, inadequate molybdenum); necrosis of hepatocytes (multifocal) results in release of copper which leads to severe intravascular hemolysis and hepatic necrosis (centrilobular and midzonal). Lysed hemoglobin products leads to dark colored kidneys and central lobular necrosis. Urine can also be dark red.
CASE: Centrolobular necrosis observed in sheep --> lamb is depressed, icterus, dark red urine 2 days duration then dead. Liver has diffuse centrilobular hepatic necrosis, kidney - tubular necrosis; kidney copper levels are elevated, liver copper levels are normal
What terriers are prone to hereditary (autosomal recessive) disorders of copper metabolism?
Bedlington terriers and WHW terriers
Hereditary disorder of copper metabolism results in
Continued copper accumulation in lysosomes (hepatic levels may be 5000ppm) --> leads to ongoing multifocal necrosis of hepatocytes, chronic inflammation, fibrosis, and end stage liver
Is hemolysis in copper toxicity a prominent feature in dogs?