liver toxicity

obligate toxic substances def

lead to predictable toxic effects, dose dependent

idiosyncratic toxic effect def

only in some individuals of some species, unpredictable, dose independent, hypersensitivity to hepatocytes

obligate toxic substances direct effects

membrane lipid oxidation

dentature structural proteins

inh enzymes

obligate toxic substances indirect effects

block recepotrs/ transport prtoeins

modify proteins

bind to nu proteins, dna, rna, ribosomes

how do exogenous posions reach liver

portal v

role of hepatocytes in detoxification

biotransformation (lipophilic hydroxylation → conjugation → bile)

hydrophilic carrier systems

kupffer cell activation → free radicals, infl

xenobiotics def

non polar foreign compounds

purpose of biotransformation

lipid soluble metabolites → water soluble for elimination via bile/urine

phases of biotransformation

1- add reactive polar groups to lipid soluble compounds / cytochrome p450 mediated oxidation

2- detoxification / conjugation

biotransformation - phase 2 conjugation happens with

water, glutathione, sulfate, glucoronate

biotransformation - how does hepatocyte damage occur

compouds metabolised by cytochrome p450 system

ischaemia, hypoxia

toxicants

acute toxic hepatosis - gross (same with any toxin)

ascites

gall bladder wall oedema

serosa petechial haemorrhage

acute toxic hepatosis - histo

centrolobular/ massive necrosis

fatty/ hydropic change

necrosis → dilated, blood filled sinusoids

acute toxic hepatosis - causes

halogenated hydrocarbons, tar derivatives, P, Cu edta, algae

effect of toxins on hepatocytes

diffuse/ zonal metabolic derangement → hydropic degeneration, lipidosis, necrosis

hydropic degeneration def

swelling cells

overall toxin effects

necrosis (regeneration depends on reticulum framework)

fibrosis

cirrhosis

hepatic neoplasms

copper toxicosis - copper deficiency disease in sheep

swayback

copper toxicosis - causes

inc intake, reduced bile excretion, genetics

copper toxicosis - which breeds predisposed (low tolerance for cu)

texels, north ronaldsay

copper toxicosis - legal max for sheep

15mg/kg

copper toxicosis - haemolytic crisis def

release of cu from necrotic hepatocytes → blood

copper toxicosis - haemolytic crisis CS

inappetance, jaundice, haemoglobinuria

copper toxicosis - histo

zone 3 necrosis, renal tubular hb casts

copper toxicosis - diagnosis def normal (150-400 microm/g)

liver cu 500-1000 microg/g

familial copper toxicosis - breed

bedlington terrier

familial copper toxicosis - cause in Bedlington terrier

autosomal recessive mutation

familial copper toxicosis - effects

hepatitis, cirrhosis

Familial copper toxicosis - histo (rhodanine stain)

Necrosis, infl, fibrosis

normal liver cu levels

<400 ppm

familial copper toxicosis - CS

inc liver enzymes, hameolytic crisis ,

copper toxicosis - copper retnetion due to

chronic liver disease → obstruct bile flow

copper toxicosis - sheep familial breed (from inc sensitivity due to low environment)

north ronaldsay

pyrrolizidine alkalosis - animals (grazing)

horse, cattle

pyrrolizidine alkalosis - cause

ing pyrrolizidine alkaloids

pyrrolizidine alkalosis - other name

ragwort, seneciosis

pyrrolizidine alkalosis - pathogenesis (chronic)

Alkaloid + cytochrome p450 → toxic pyrrolic esters → bind to DNA

pyrrolizidine alkalosis - gross

bile duct proliferation, hepatoencephalopathy, cirrhosis

pyrrolizidine alkalosis - histo

single cell necrosis, megalocytes, infl, fibrosis

megalocytosis def

inh mitosis but not protein synthesis → large cells

CS of liver failure

ascites, jaundice, hepatic encephalopathy

aflatoxicosis - cause

mouldy feed

aflatoxicosis - fungi species making toxins (furanocumarin)

aspergillus flavus, aspergillus parasiticus, penicillium puberculum

aflatoxicosis - effects

carcinogenic, teratogenic, inh mitosis, immunosuppressive, chronic hepatotoxicity

aflatoxicosis - liver change s

inh mitosis, megalocytosis, lobular shrinkage, fibrosis

blue green algae - group names

cyanobacteria

blue green algae - liver effects from algae digestion

centrolobular/ massive necrosis with haemorrhage