6-Renal Toxicity Flashcards
1
Q
Renal toxicants
A
- Ethylene glycol
- Cholecalciferol/Vitamin D3
- Grape and raisin tox
2
Q
Hepatic toxicity
A
Acetaminophen
3
Q
Kidney is common site of toxicity
A
- High blood flow (22-25% cardiac output)
- Concentration of compounds
- tubular concentration can be 600X that of plasma
- Can lead to crystallization
- oxalic acid
- Most imp organ for excretion of zenobiotics
- dep on water solubility of toxican
- high lipid solubility of xenobiotics
- resorbed across tubular cells into bloodstream again
4
Q
Proximal Convoluted Tubule
A
-
most common site of toxin induced injury
- cytochrome P450 and cysteine conjugate Beta-lysase localized here
- phase one detox enzymes
- bioactivation => damage
- Loose epithelium allows compounds to enter cells
- Inc transport => ischemic injury to epithelial cells
- anions
- cations
- heavy metals
- cytochrome P450 and cysteine conjugate Beta-lysase localized here
5
Q
Acute Renal Failure
A
- Decreased GFR and renal azotemia
- Caused by transient damage to tubule, glomerulus or vasculature
- Signs
- vomiting
- GI bleeding
- PUPD => anuria
- diarrhea
- tremors
6
Q
Chronic Renal Failure
A
- Mostly related to secondary pathological changes triggered by initial injury
- Secondary changes are compensatory mechanisms
- Signs
- edema
- hypocalcemiaparathyroid activity
- inc Ca in blood
- Calcitonin puts Ca back into bone
- reduced RBC count
7
Q
Ethylene Glycol
A
- Major ingredient in normal antifreeze
- 2nd most common cause of fatal poisonings in animals
- Most frequently used for malicious poisoning
- Exposure common in Spring and Fall when people change antifreeze
- Very high rate of lethality (80%)
- delay of clinincal symptoms and presentation
- Tastes sweet
- 1 tbspn can kill a cat
- 7 mL can kill a dog
8
Q
Ethylene glycol
MOA
A
- Metabolites caused by action of alcohol dehydrogenase are toxic
- glycolic acid
- acidosis
- possibly CNS signs
- oxalate/oxalic acid
- causes renal damage and hypocalcemia
- binds to calcium to form calcium oxalate
- causes renal damage and hypocalcemia
- glycolic acid
9
Q
Stages of ethylene glycol poisoning
A
- Stage 1: 30 minutes-3 hours
- drunkenness, ataxia, CNS depression
- nausea, vomiting
- PU/PD (dogs)
- Usually missed with unobserved ingestions
- Stage 2: 12-24 hours
- tachypnea, tachycardia (rarely bradycardia)
- cats typically remain depressed
- signs often not recognized by owner
- Stage 3: 12-72 hours
- most animals present in this stage
- polyuria => oliguria => anuria
- Lethargy, anorexia, vomiting, seizures
- Oral ulcers, abdominal pain, dehydration, enlarged kidneys
10
Q
Ethylene glycol tox
Diagnosis
A
- measuring EG conc in blood
- serum conc peak at 1-6 hours
- no detection in serum and urine by 24 hours
- cats can be poisoned by levels below detection of many kits
- Azotemia
- Elevated BUN and creatinine in Stage III
- Urinalysis
- low USG (1.008-1.012 in dogs w/in 3 hours)
- crystalluria (w/in 6 hours)
- Calcium oxalate crystals in kidney via ultrasound exam
- Shine a UV lamp
11
Q
Ethylene glycol toxicity
Serum biochem
Anion/osmol gap
A
- Serum biochem profile
- hyperglycemia
- hypocalcemia
- Anion and osmol gap
- metabolites inc unmeasured anions resulting in anion gap
- anion gap > 30 (normal is 10-25)
- Osmol gap > 20 (normal is 10)
- serum osmolality can reach 450 mosm (nor al is ~300)
- Ddx
- rhubarb
- pigweed
- defebechia…?
12
Q
Ethylene glycol tox
Treatment
A
- prevent formation of toxic metabolites
- Achieved through administration of competitive inhibitors of alcohol dehydrogenase
- 20% Ethanol and sodium bicarb (acidosis)
- monitor CNS depression and ethanol administration
- antagonized by fomepizole (bad!)
- Fomepizole (4-methypyrazole, 4-MP) or Antizol
- 20% Ethanol and sodium bicarb (acidosis)
- No benefit of ethanol or 4-MP if ethylene glycol has already been metabolised
- contraindicated in animals with renal failure
- no activated charcoal or emesis if 72 hours later (stage 3)
13
Q
Ethylene Glycol Toxicity
Prognosis
A
- Cats
- peak plasma conc about 1 hour after ingestion
- survival highly dependant on tx w/in first 3-4 hours
- mortality rate at least 90%
- Dogs
- peak plasma concentration occurs at 2-3 hours
- survival most likely tx if started w/in 6-8 hours of ingestion
- azotemia on admission => slim chance
- Renal failure => poor prognosis
- Survivors
- therapy often required for up to 72 hours
- recovery can take 3-5 days if treated aggressively
14
Q
Cholecalciferol / Vitamin D3
A
- Overdose of vitamin supplements
- exposure to rodenticide
- toxic at > 0.5 mg/kg
- lethal 10-15 mg/kg
- Dogs and cats most affected
15
Q
Cholecalciferol / Vitamin D3
MOA toxicity
A
- Cholecalciferol metabolized to 1,25-dihydroxycholecalciferol
- causes massive inc in serum calcium
- inc GI absorption
- dec renal excretion
- inc synthesis of Ca binding protein
- mobilizing bone Ca
