Liver and Pancreas 4, 5 and Practical Flashcards
What are obligate and idiosyncratic toxic substances?
What can the mode of action be for obligate toxic substances?
How do exogenous proteins reach the liver
Obligate- leads to predictable toxic effects in numerous species- dose-dependent, direct or indirect on hepatocytes- paracetamol
Idiosyncratic- only in some individuals of some species- unpredictable, dose independent
Obligate direct effect-
oxidation of membrane lipids, denaturation of structural proteins, inhibition of enzymes
Indirect effects-
blocking of receptor or transport proteins, modification of proteins, binding to nuclear proteins- DNA, RNA
Exotoxins to liver via portal blood- intestine
What are the roles of hepatocytes in detoxification?
Biotransformation- hydroxylation and subsequent conjugation of lipophilic substances
mainly performed by centrilobular
Carrier systems for uptake of water-soluble substances from blood and secretion via bile
Activation of kupffer cells via receptors (endotoxins)- release of free radicals and inflammatory mediators
Where does most damage occur during biotransformation to hepatocytes?
Dominance of zone 3- centrilobular hepatocytes- injury with compounds metabolised by CytP450
Zone 3 prone to ischaemia/hypoxia
Dominance of zone 1 injury with direct-acting toxicants
What are the gross and histological findings of acute toxic hepatosis, independent of the toxin?
Gross-
ascites
oedema of gall bladder wall
petechial haemorrhage in the serosa
Histo-
Usually centrilobular to massive necrosis, often with a fatty hydropic change of adjacent hepatocytes
Early-stage- degenerate/necrotic hepatocytes still orderly arranged
Late-stage- dilated, blood-filled, sinusoids
What is the effect of toxic substances on hepatocytes and overall?
Effect on hepatocytes-
Diffuse or zonal metabolic derangement- hydropic degeneration, lipidosis or necrosis
Over all-
One-time submissive necrosis- regen possible
One time massive necrosis with destruction of reticular framework- fibrosis
Chronic or recurrent toxin application- chronic active hepatitis- cirrhosis
Some toxins- hepatic neoplasms
What does copper deficiency cause in sheep and cattle?
What can cause copper toxicity cause in sheep?
Deficiency-
Sheep- swayback
Cattle- coat and pigment abnormalities
Toxicity-
High intake, reduced biliary excretion, familial predisposition
Pasture contamination- high Cu in pig/poultry slurry
Inadvertent feeding- pig/cattle diets
Nutritional imbalance of Mo- Cu and Mo form complexes
Consumption of hepatotoxic plants
Breed susceptibility- merino most resistant, Texel most
Stress- transport
Describe the clinical-pathological manifestation of copper toxicosis in sheep
Accumulation of Cu in the liver to over normal with minimal effect
Haemolytic crisis-
- release of Cu from necrotic hepatocytes into normal blood
- may be precipitated by ingestion of hepatotoxin
- Histological changes- liver necrosis of zone 3, renal tubular Hb casts
Diagnosis- liver copper 500-1000mg/g
What is familial copper toxicosis in dogs?
What is copper associated liver disease and what canine breeds are predisposed?
Familial copper toxicosis in dogs-
Due to autosomal recessive mutation
Cu accumulates in liver zone 3 with progressive hepatitis and ultimately cirrhosis
Copper-associated liver disease
Copper retention can occur secondarily to chronic liver disease in which there is failure or obstruction to bile flow-
Chronic active hepatitis in Doberman
Syke terrer hepatitis
What are the alternative names for ragwort poisoning?
When does ragwort grow?
What are the toxic mechanisms of ragwort?
What are the pathological findings?
Pyrrolizdine alkaloidosis, seneciosis
Biennial-
during first year the plant produced a root, a short step and leaves a flat rosette
The second-year- plant develops tall stem and yellow flowers
Toxic mechanisms-
the cumulative effect- chronic hepatotoxicity
Alkaloids themselves are not toxic
cytochrome P450 produces toxic pyrrolic esters
Sensitivity- pig, cattle/horse, sheep- most to least sensitive
Pathological findings-
Hepatic cirrhosis
Single-cell necrosis
Megalocytes- regenerative attempt- inhibition of mitosis
Inflammatory infiltration, fibrosis
Bile duct proliferation
Hepatoencephalopathy
What is consumed for alflatoxicosis?
What causes the toxic effect?
What are the effects similar to?
What species are sensitive?
Due to the consumption of mouldy feedstuffs
Aspergillus flavus
Chronic hepatoxicity
Liver changes- similar to senecoisis
Sensitive- dogs, cats, pig, calf
What causes blue-green algae poisoning?
What species is it seen in?
What liver changes does it cause?
Due to toxic, fresh water, blue-green algae
Seen in cattle, sheep, horse, pig, dog
Acute hepatotoxicity- when algae degenerate
Centrilobular to massive necrosis with haemorrhage
What artery does the pancreas receive blood from and where does blood leave?
How do different species secrete from the pancreas?
Arterial blood- cranial mesenteric and celiac arteries
Venous- portal vein
Secretion-
Major pancreatic duct into duodenum at duodenal papilla-
only present in sheep, goats and cats- always in horses
Minor pancreatic duct into duodenum at accessory duodenal papilla-
only duct in swine and cattle, often only in dogs- always in horses
The pancreas produced and secretes digestive enzymes
How does it prevent autodigestion?
- Synthesis/storage of inactive proenzymes
- Storage of enzymes in zymogen granules separated from lysosomes
- Activation of enzymes distant from pancreas
- Protection of ductal epithelial cells by mucus layer
- Secretion of specific inhibitors of trypsin and nucleases
- Circulating protease inhibitors
What digestive enzymes does the pancreas secrete and what controls the secretion?
Proteases-
trypsin- activated by enterokinase in intestinal mucosa
Chymotrypsin- activated by trypsin
Lipase-
Amylase-
Control-
Cholecystokinin- secreted by endocrine cells in the duodenum into blood
Secretin- endocrine cells in cranial SI in response to acid, stimulates water and bicarb in pancreas
Gastrin- secreted by stomach in response to digestion
What are the different anomalies of the development of the pancreas?
Aplasia- very rare, incompatible with life
Hypoplasia- occurs sporadically in calves
clinically EPI exocrine pancreatic insufficiency
Juvenile atrophy-
young dogs (GSH)
Histo- exocrine tissue most absent, islets unaffected
Clinical signs- chronic EPI, fat-rich faeces
Haemorrhage-
mainly seen in dogs
with coagulation disorders- infection/intoxication
This is an ultrasound from a dog with pancreatitis, what are the hyperechoic/hypoechoic regions in the middle of the scan?
What are the outcomes for dogs with acute necrotising pancreatitis?
Hypoechoic- black- irregularly shaped inflamed pancreas
Hyperechoic- white- surrounding areas of peritonitis
Outcome-
death within a few days- consumption of plasma protein inhibitors, activation of kinin, coagulation, fibrinolysis, complement cascade-> DIC, shock
Animals survive and develop repeated acute episodes-
chronic fibrosing pancreatitis, exocrine pancreatic insufficiency, diabetes mellitus
What causes chronic fibrosing pancreatitis?
How does it histologically appear?
What can cause it in cats?
Sequel to acute necrotising pancreatitis
Histology-
Pancreatic tissue replaced by fibrous tissue
Cats-
chronic interstitial pancreatitis with chronic cholangitis- bile duct and pancreatic duct fuse before duodenum
What are the neoplasms of the exocrine pancreas?
Nodular hypoplasia-
not a neoplasm
older dogs, cattle and cats
multiple, no encapsulation, no compression of adjacent tissue
Adenoma-
very rare, usually solitary
Adenocarcinoma
