Renal & Hepatic Flashcards
Why kidneys are susceptible to effects of toxicity
High blood flow
High concentration of toxins
Critical for excretion of xenobiotics
Most common site of kidney for toxin-induced injury
Proximal tubule
Because:
Cytochrome p450 and cysteine conjugates can bioactivate toxins
Loose epithelium allow compounds to enter cells
Increased transport of anion, cations, and heavy metals causes accumulation and can cause ischemic injury to epithelial cells
Characteristics of ethylene glycol
Antifreeze
2nd most common of fatal poisonings in animals
Most frequently used for malicious poisonings
Exposure most common in spring and fall when people change their antifreeze
Very high rate of lethality (80%) due to delays in presentation
Tastes “sweet”
Lethal dose of ethylene glycol in cats
1.5 ml/kg of undiluted antifreeze
About 1 tbsp of 50% antifreeze
Lethal dose of of ethylene glycol in dogs
7 ml/kg of undiluted antifreeze
4.5oz of 50% antifreeze
Mechanism of action in ethylene glycol toxicity
- Glycolic acid causes acidosis
- Glyoxylic acid causes CNS signs
- Oxalate/oxalic acid causes renal damage and hypocalcemia
Stage 1 of ethylene glycol toxicity
30 min - 3 hours after ingestion
“Drunkenness”, ataxia, CNS depression
Nausea, vomiting
PU/PD (dogs)
Usually missed with unobserved ingestions
Stage 2 of ethylene glycol toxicity
12-24 hours post ingestion
Tachypnea, tachycardia (or bradycardia)
Often not severe and not recognized by owner
Cats typically remain depressed
Stage 3 ethylene glycol toxicity
12-72 hours post ingestion
Most animals present in this stage!
Polyuria progression to oliguria and anuria
Lethargy, anorexia, vomiting, seizures
Oral ulcers, abdominal pain, dehydration, enlarged kidneys
Diagnosis of ethylene glycol toxicity
Best method is measuring EG concentration in blood (peak concentrations at 1-6 hours, undetectable by 24 hours)
Chem panel: elevated BUN and creatinine in Stage 3, hyperglycemia, hypocalcemia, increased anion gap
Urinalysis: low SG, crystalluria
Calcium oxalate crystals in kidney
Treatment of ethylene glycol toxicity
Goal: prevent formation of toxic metabolite
Give 20% ethanol + sodium bicarbonate, or fomepizole
No benefit if E.G. Has already been metabolized
Prognosis of EG toxicity (cats and dogs)
Cats: prognosis best if treated in first 3-4 hours, 90% mortality rate
Dogs: prognosis best if treated in the first 6-8 hours
Renal failure indicates poor prognosis for both
For the survivors: therapy may be needed every 72 hours, treatment may take 3-5 days
Why is sodium bicarbonate given with ethanol in treatment of ethylene glycol toxicity?
Correct metabolic acidosis
Why would you not use decontamination as a treatment for ethylene glycol toxicity?
It is rapidly absorbed in stomach so these treatments would be ineffective unless the ingestion was observed/could treat within 1 hour of ingestion
Sources of cholecalciferol (Vit D3) that may cause toxicity
Vitamin supplements
Some rodenticides
Mechanism of action of cholecalciferol (Vit D3)
Is metabolized to 1,2 dihydroxycholecalciferol
Causes massive increases in serum calcium by:
Increasing GI absorption
Decreasing renal excretion
Increased synthesis of Ca binding protein
Mobilizing bone calcium
Clinical signs of cholecalciferol (Vit D3) toxicity
Signs usually appear 36-48 hours after ingestion
Anorexia, weakness, depression
Thirst and polyuria
Diarrhea, dark feces due to intestinal bleeding
Vomiting
Hypertension
Bradycardia, ventricular arrhythmia
Mineralization of tissues when Ca * P >70 mg/l
Diagnosis of cholecalciferol (Vit D3) toxicity
Based on history of ingestion, clinical signs, and hypercalcemia
Rapid increased in P followed by increase in plasma Ca
Low PTH
Increased BUN, creatinine
Low urine SG with calciuria
High hydroxycholecalciferol levels in bile and kidney
Differential diagnoses for cholecalciferol (Vit D3) toxicity
Mineralization in multiple organs
Ethylene glycol
Paraneoplastic syndrome
Juvenile hypercalceimia
Hyperparathyroidism
Treating cholecalciferol (Vit D3) toxicity
GI decontamination within 6-8 hours Monitor and reduce dietary Ca and P Saline, furosemide Prednisolone Pamidronate Sucralfate or milk of magnesia for ulceration
Mechanism of action of grape/raisin toxicity
UNKNOWN
Major result of grape/raisin toxicity
Renal failure
Clinical signs/diagnosis of grape/raisin toxicity
Vomiting followed by symptoms of acute renal failure
Hypercalcemia
Hyperphosphatemia
Increased CaPO4
Elevated BUN and serum creatinine
Treatment of grape/raisin toxicity
Recommended following ingestion of ANY quantity
Emesis, lavage, activated charcoal
Fluid therapy for a min 72 hours
Furosemide
Other supportive therapies: Dopamine, mannitol, hemodialysis, peritoneal dialysis
Mechanism of action of acetaminophen toxicity
Metabolized bin liver by glucuronidation, sulphonation, and oxidative pathways that result in the formation of NAPQI (causes most of the damage)
NAPQI binds macromolecules and proteins to cause liver tissue necrosis and causes erythrocytes injury (MetHb and Heinz bodies)
Cats especially susceptible!
Clinical signs of acetaminophen toxicity
MetHB, Heinz bodies
Hepatotoxicity, Liver necrosis
Tachycardiaa, hyperpnea, weakness, lethargy
Diagnosis of acetaminophen toxicity
Cats: cyanosis, MetHb, dyspnea, weakness, depression, edema of face/paws, anemia
Dogs: centrilobular hepatic necrosis, nausea, vomiting, anorexia, abdominal pain, tachypnea, tachycardia
Treatment of acetaminophen toxicity
REPLENISH GLUTATHIONE STORES! Give NAC (N-acetylcysteine)
Early decontamination if possible
Decreased MetHb by giving ascorbic acid (Vit C)
Cimetidine
Antioxidants
Supportive care
