Renal Toxicants Flashcards
What is the most common site of renal injury and why?
The proximal convoluted tubule is most sensitive to toxicosis. It is the first site to receive renal filtrates, has high levels of Cytochrome P450 to form toxic metabolites, has loose epithelium allowing influx of substances, and has increased transport of anions, cations and heavy metals.
What are signs of acute renal failure?
Vomiting, GI bleeding, polyuria/polydipsia progressing to anuria, diarrhea, and tremors
What are signs of chronic renal failure?
Edema, hypocalcemia (due to decreased vitamin D conversion), increased parathyroid activity, and reduced red blood cell counts (due to decreased erythropoetin)
What are the 3 stages of ethylene glycol toxicity and describe them?
1) 30min-3hrs Ethylene glycol reaches peak plasma concentration = CNS depression and ataxia
2) 12-24hrs Cardiopulmonary Effects = tachycardia and tachepnia
3) 12-72hrs Renal Effects = oxalic acid metabolites precipitate in blood stream and renal tubules causing renal faluire
How do you treat ethylene glycol toxcicity?
Main goal is to prevent formation of oxalic acid metabolite: Use of 20% Ethanol (competitive inhibition of alcohol dehydrogenase) and sodium bicarbonate (treats metabolic acidosis) with fluids to diurese or use of Fomepizole (antidote to ethylene glycol, but costly)
What is the enzyme responsible for metabolizing ethylene glycol?
Alcohol dehydrogenase
Would it be a good idea to use activated charcoal with ethylene glycol ingestion?
No. Activated charcoal will not bind organic substances like ethylene glycol
What is the mechanism of toxicity of cholecalciferol (Vit D)?
It causes a massive increase of serum calcium and Phosphorus levels via 1) Increased GI absorption, 2)Decreased renal excretion of Ca, 3)Increased expression of proteins that mobilize Ca, and 4)increasing resorption of Ca from bone.
What are the clinical signs of Cholecalciferol toxicity?
Calcium precipitates in kidneys leads to depression, weakness, thirst, and polyuria.
Calcification of vessels and organs causes GI bleeding, diarrhea, and vomiting
High serum Ca causes hypertension, bradycardia, and arrythmias
How do you diagnose cholecalciferol (Vit D) toxicity?
As bone breaks down, serum phosphorus will rise, and then serum Ca will rise. PTH will be low.
BUN and CRE will rise as kidneys become damaged and you will see low spec grav with calciuria (~4000ppm wheras EG toxcicity will be higher at ~8000ppm)
High hydroxycholecalciferol levels in bile and kidney.
How do you treat Vit D toxicity?
Saline and furosemide to help with Ca excretion
Prednisolone - reduces aborption/resorption of Ca in GI, bones, and kidney
Calcitonin or Pamidronate to inhibit bone resorption (but effects are unpredictable with Calcitonin, and Pami is $$)
Sucralfate or Milk pf magnesia helps prevent GI ulcers and helps bind Phosphate
What supportive therapies are there to treat grape toxicity?
Furosemide - promotes diuresis and kidney function
Dopamine - facilitates renal blood flow
Mannitol - renal protectant
Fluids for a minimum of 72hrs
What is the mechanism of Acetaminophen toxicity?
Highly reactive metabolite NAPQI (N-acetyl-p-benzoquinone imine) causes oxidative and mitochondrial damage.
What two animals are particularly sensitive to Acetaminophen and why?
Cats - lack of glucouronidase to metabolize
Pigs - lack of sulphonidase metabolize
What effects does Acetaminophen toxicity have in cats?
Oxidative damage to RBCs and methemoglobin
