Toxicology Flashcards
xenobiotic
a poison or toxin
exogenous chemicals that can be absorbed into the body
mechanism of xenobiotics
ADME
Absorption
Distribution
Metabolism
Excretion - by kidneys if water soluble, bile if lipid soluble but can also accumulate in fat
metabolism
2 phase -
phase 1 - produces derivatives to be processed through phase 2 - oxidation, reduction, hydorlysis. used CP450
Phase 2 - conjugation - joining with other substances for elimination (uses glucornyl transferase as well as other things - cats don’t have so not as good at this)
directly toxic - toxic in original form
toxic metabolites - form after phase 1 is toxic (eg ethylene glycol, organophosphates)
gross and hist appearance of liver in toxicity
diffuse liver enlargement - acute
zonal necrosis (usually always toxicity or hypoxia) - acute centrilobar
(if random necrosis - more likely blood bourne bacteria)
massive necrosis - spreading from centrilobar - iron toxicity in pigs, vitamin E/selenium deficiency, xylitol in dogs
post mortem samples
liver - toxicity
spleen - haemangiosarcoma
lungs - e coli
heart - congestive heart failure
fat - fat soluble toxins - more chronic
kidney (fixed) - ethylene glycol crystals
ethylene glycol
absorbed from GIT –> bloodstream to liver –> metabolised by gastric mucosa and liver by mucosal alcohol dehydrogenase –> toxic metabolites (oxalic acid)
IV alcohol - competes for the alcohol dehydronenase
causes severe metabolic acidosis
binds with blood calcium to leave calcium oxalate crystals in kidneys, brain, heart and lungs
hypocalcemia
renal azotemia
renal damage –> acute tubular necrosis
diagnosis -
azotemia
hypocalcemia
metabolic acidosis
calcium oxalate crystals in urine
flourescent urine under UV
post mortem - bilaterally enlarged kidneys, gritty, deposition of calcium crystals, multifocal white streaking in cortex
anticoagulant rodenticide poisoning
anticoagulant causes rodents to bleed to death
inhibits vitamin k –> interferes with secondary homeostasis –> large haemorrhages
treat with activate charcoal and come back or give vitamin k
diagnosis -
increased PT and aPPT
regenerative anemia
normal buccal mucosal bleeding time
post mortem - haemorrhage into intestine and body cavities, toxicology testing on stomach contents
not much on histo
vitamin D3 poisoning (cholecalciferol)
found in rodenticides and some human medicines (psoriasis cream)
metabolised by liver and kidney –> calcitrol –> enhances calcium absorption from bone, gut and urine –> hypercalcemia –> calcium deposition in stomach and kidney
diagnosis -
azotemia
hypercalcemia
post mortem - soft tissue mineralisation (gritty stomach wall, serosal surfaces, kidneys)
crystals on stomach and kidneys in histo
NSAID toxicity
inhibit COX –> inhibited prostglandin production –> vasoconstriction –> renal failure from infarction + stomach ulcers
kidney necrosis
mild buccal mucosal bleeding time increase
hepatotoxins
toxins primary affecting the liver
xylito
alfatoxins
amanita mushrooms
blue green algae - seizures, rapid liver failure
heavy metals - copper
pesticides - acute liver failure
paracetamol - cats
idiosyncratic drug reactions
liver failure - jaundice, raised ALP and ALT, low albumin, secondary coagulopathy, increased bilirubin, increased ammonia
DIC –> multi organ fialure
zonal necrosis in liver
hepatic encephalopathy - neurological signs from liver failure
copper toxicosis - dogs and sheep
copper - co factor in lots of functions - mitochondrial respiration, collagen cross linking, formation of anti oxidants, production of melanin (loss of dark colour)
dogs-
more chronic
free radical formation –> accumulation in nucleus –> DNA damage –> apoptosis
altered biliary excretion or excess in diet
bedlington terriers - genetic defect - need low copper diet
pm - shrunken liver, cirrhosis
histo - centrilobar degeneneration but chronic (fibrosis), evidence of reversible injury, regeneration (multiple nuclei in hepatocytes), stains for intracellular copper
sheep -
accidental ingestion of cattle feed
acute crisis
toxic to hepatocytes and erythrocytes
acute liver failure and intravascular haemolysis (haemoglobinuria)
variable liver appearance, bilaterally dark red enlarged kidneys
paracetamol - cats
phase one metabolism by CYP450 –> toxic metabolite
can’t do phase 2 to excrete because cats don’t have glucothione
oxidative stress and damage to erythrocytes –> oxidate iron in blood to methemaglobin –> lack of oxygen transport
cyanosis
brown mm (colour of methemaglobin)
heinz bodies (denature methemabolbin precipitates on RBCs)
eccentrocyte formation
oxidative injury of erythrocytes - toxins
paracetamol
chocolate - PUPD, tachycardia, tremors, seizures, pancreatitis
grapes/raisins - renal failure
metaldehyde (slug bait) - sudden onset neuro signs - seizures)
cannabis - ataxia, bradycardia, hypothermia, vacolisation, urinary incontinence (dribbling urine constantly)
avocado - cardiotoxic
carbon monoxide poisoning
CO has high affinity for haem than oyxgen –> competes with oxygen for binding –> reduced oxygen carrying capacity
mass death
post mortem - cherry red mm and organs
ragwort toxicity
most common liver plant toxin
pyrrolizidine alkaloids in plant converted to toxic enzymes –> prevent replication of liver cells –> centrilobular necrosis with megalocytosis (massive nucleus)
^ only toxin that really does this
usually chronic - fibrosis, billiary hyperplasia, regenerative nodules
elevated liver enzymes
in herbivores - photosensitisation - chlorophyll not metabolised, toxins react with sunlight when reach the skin
