Urinary Toxicology, Pt. 2 Flashcards
What are some oxalate-containing plants that are nephrotoxic? What animals are most susceptible?
- beets and docks (Rumex spp.)
- Halogeton spp.
- lamb’s quarter (Chenopodium spp.)
- greasewood (Sarcobatus)
- rhubarb (Rheum spp.)
- soursob (Oxalis cernua)
- Setaria, Kochia, Amaranthus
livestock (mostly sheep and cattle) and companion animals
What is the mechanism of toxicity of oxalate-containing plants? What is partly responsible for renal cell damage?
soluble oxalates bind to serum calcium to form calcium oxalate, which cases hypocalcemia and crystalizes in the kidney, causing tubular necrosis
free radical production (scavengers were shown. to reverse renal damage
What causes clinical signs associated with oxalate-containing plant toxicosis? What are the most common clinical signs?
hypocalcemia
- muscle tremors, tetany, seizures
- weakness, incoordination, reluctance to move, recumbency
- depression coma
- rumen atony, bloat
- teeth grinding, slobbering
- bradycardia
- vomiting, increased BUN and weight loss in those that do not die acutely
How is oxalate-containing plant toxicosis diagnosed? What 3 treatments are recommended?
plant identification, calcium oxalate crystals in kidneys, oxalate in forage
- SMALL ANIMALS: induce emesis and give dairy products, like milk or yogurt to bind oxalate
- dicalcium phosphate:sodium chloride (1:3) binds oxalates in gut
- IV fluid in animals with renal insufficiency
What species is especially susceptible to Lilium and Hemerocallis (lily) toxicity? What is the toxic principle?
cats
unknown water-soluble toxin found in the leaves and flowers
What is the mechanism of toxicity of Lilium and Hemerocallis (lily)? What are the 2 components necessary for acute renal failure?
renal tubular epithelial cell damage
- direct action of the toxin(s) on the renal tubular epithelium resulting in cellular damage
- severe dehydration due to polyuria
When are most cases of Lilium and Hemerocallis (lily) toxicity common? What are the initial and later clinical signs?
1-3 weeks after Easter
- INITIALLY: depression, vomiting, anorexia, salivation, progressive weakness
- LATER: PU followed by dehydration, anuria,and recumbency
What treatment is recommended for anuric patients with Lilum and Hemerocallis (lily) toxicity?
- correct dehydration and impose fluid diuresis (2-3x amount of maintenance)
- peritoneal dialysis or hemodialysis
What species is most susceptible to grape and raisin toxicity?
dogs, maybe cats and ferrets
all types and colors of grapes/raisins are toxic and toxic dosage varies widely
What is thought to be the toxic principle of grapes and raisins? What are 3 reasons this is hypothesized?
tartaric acid and potassium bitartrate
- toxicity of potassium bitartrate is characterized by similar clinical signs and proximal renal tubule damage as grapes and raisins
- exposure to tamarinds, which are uniquely ricj in tartaric acid, cause similar severe vomiting and acute renal failure in dogs as grapes and raisins
- grapes contain high levels of both, with levels varying depending on growing conditions and ripeness
What are 5 other additional toxins suspected to be present in grapes/raisins?
- ochratoxin
- flavonoids
- polyphenols
- tannins
- monosaccharides
Why is rapid absorption of grape and raisin toxins suspected? What describes why a clear dose-response curve has not been established yet?
toxicosis has rapid onset
variation in the number of toxic principles or varying sensitivities among individual dogs
Where is the injury to the kidneys most concentrated with grape/raisin toxicity? What does this result in? What may explain the variability in toxicosis?
proximal renal tubular epithelium
idiosyncratic reaction resulting in hypovolemic shock and renal ischemia
variability in tartaric acid and potassium bitartrate in grape types, different growing conditions, and ripeness
What clinical sign is first noted with grape/raisin toxicity? What develops?
vomiting within 6-12 hr of ingestion, likely due to direc effect of the toxins on the GIT or from uremia secondary to renal failure
- diarrhea, anorexia, lethargy
- abdominal pain, weakness, dullness
- dehydration isosthenuria, oliguria/anuria
- increased BUN and creatinine within 24 hours
- hypercalcemia, hyperphosphatemia, hyperkalemia
- anuric renal failure leads to death or euthanasia
What treatments are used to combat renal failure in grape/raisin toxicity? What symptomatic/supportive treatments are recommended?
- Furosemide
- Dopamine
- Mannitol
- hemodialysis/peritoneal dialysis
VOMITING - antiemetics
IV FLUIDS - monitor central venous pressure in anterior vena cava and uring production for potential fluid overloas
What is Amphotericin-B? What is the major factor that limits its use?
antifungal - Fungizone, Amphotec, AmBisome used to treat candidiasis, aspergillosis, and histoplasmosis
nephrotoxicity
What is the ADME of Amphotericin-B like? What animals are most susceptible?
- poor oral absorption
- highly bound to plasma proteins
- slowly eliminated in urine and bile
cats
What are the 3 mechanisms of toxicity of Amphotericin-B?
- renal arteriolar vasoconstriction causing a reduction in renal blood flow and GFR, causing ischemic injury and uremia
- forms intramembranous pores in the renal tubules causing dysfunction due to increased permeability, which leads to excess monovalent ions delivered to the distal tubule and a decrease in GFR due to tubuloglomerular feedback
- antagonizes ADH, causing an impairment or urine concentrating ability —> PU
What renal signs are associated with Amphotericin-B toxicity? What risk factors increase the likelihood of these developing?
ACUTE RENAL FAILURE
- PU, oliguria, anuria
- hematuria, proteinuria
- increased casts in urine sediments
- increased BUN and creatinine
- fever, depression, anorexia, nausea, vomiting, diarrhea, anemia
dehydration and pre-existing renal disease
What treatments for Amphotericin-B is recommended?
- discontinue drug administration
- provide aggressive fluid therapy to prevent further renal damage wth Mannitol
- monitor PCV, TP, BUN and creatinine and stop therapy when BUN becomes normal
What are 3 types of Aminoglycosides? What is the mechanism of toxicity?
- Gentamicin
- Kanamycin
- Neomycin
nephrotoxicity and ototoxicity, especially in cats
Where do Aminoglycosides accumulate? What are 2 results of this?
renal proximal tubule cells and endolymph of ear
- myeloid body (concentric lamellae of phospholipids) formation in lysosomes of renal tubular cells, which causes rupture of the lysosomes and the release of its enzymes —> cell death
- interacts with ribosomes and mitochondria, resulting in impairment of protein and ATP synthesis —> cell death
What are renal signs of Aminoglycoside toxicity attributed to? What risk factors increase susceptibility?
acute tubular necrosis and ARF
- anorexia, vomiting, depression
- PU, proteinuria, glucosuria, casts, uremia
dehydration, extended duration of therapy, large dose, renal disease, age
How do Aminoglycosides cause ototoxicosis? What are the 2 major dysfunctions?
damages cranial nerve VIII - vestibulocochlear
- VESTIBULAR - nystagmus, incoordination, loss of righting reflex
- AUDITORY - loss of high frequency hearing due to damage of hair cells in the organ of Corti
What are 3 major sources of cholecalciferol (vitamin D3)? What species are susceptible to toxicosis?
- vitamin D-containing plants, like Cestrum spp. (day blooming jasmine)
- vitamin supplements
- rodenticides
cats*, dogs, swine, horses
Why is cholecalciferol (vitamin D3) slowly eliminated? How is it distributed? What happens when it reaches the liver?
fat-soluble
bound to vitamin D-binding protein (α2-globulin) in plasma
metabolized and circulated as calcifediol, which is then activated in the renal proximal tubule into calcitriol
What are the 3 mechanisms of toxicity of cholecalciferol (vitamin D3)? What does it commonly work in conjunction with?
- enhances plasma calcium and phosphorus absorption from the gut by increasing the amount of intestinal calcium-binding protein (calbindin)
- stimulates calcium and phosphorus transfer from blood to plasma
- increases renal calcium reabsorption
PTH
What causes clinical signs associated with cholecalciferol (vitamin D3) toxicity? What signs are most common?
hypercalcemia and hyperphosphatemia
- depression, vomiting/hematemesis, diarrhea/malena
- constipation, anorexia
- PU/PD, calcuria, dehydration
- cardiac arrhythmias
- seizures
- mineralization of soft tissue
How are symptomatic patients with cholecalciferol (vitamin D3) toxicity commonly treated? What is given to those that do not respond?
- diuresis with caline at 2-3x maintenance rate
- Furosemide: increase renal calcium excretion
- Prednisone: decreases serum calcium by reducing GI absorption and increases excretion
- salmon calcitonin: lowers plasma calcium by inhibiting osteoclastic activity
Biphosphonate - lowers plasma calcium by inhibiting bone resorption
What supportive care is recommended for patients with cholecalciferol (vitamin D3) toxicosis?
- hydration
- phosphate binders: aluminum hydroxide
- low-calcium low-phosphorus diet
What are the main sources of melamine and cyanuric acid?
MELAMINE: resins used as laminates, adhesive, moldings, plastics, cleaners, glues, yellow dye, and flame retardants; fertilizer (high nitrogen), dog food (fraudulently increased apparent protein)
CYANURIC ACID: melamine analogue produced during melamine synthesis and degradation used to stabilize chlorine in swimming pools, bleach, disinfectants, and herbicides
What is toxicity of melamine and cyanuric acid like?
low toxicity individually, but toxicity increases dramatically when combined
What is metabolism of melamine and cyanuric acid like in monogastrics and ruminants and poultry? How is it excreted? How is this different in sheep?
- MONOGASTRIC: minimal metabolism
- RUMINANTS/POULTRY: partially metabolized and secreted in milk/eggs
unchanged in urine
54% urine, 24% feces
What is the mechanism of toxicity of melamine and cyanuric acid? What additional effect does melamine have?
crystal formation in renal tubules causes acute intra-renal obstruction, inflammation, obstruction due by proteinaceous material secondary to casts, and cell death
acts as a diuretic that can cause pre-renal azotemia
How does melamine cyanurate crystals form?
melamine and cyanuric acid dimerize and become insoluble, causing renal tubule occlusion and necrosis
What are the early signs of melamine and cyanuric acid toxicosis? What signs follow?
depression, vomiting, anorexia
RENAL FAILURE - increased BUN, creatinine, and anion gap, PU/PD, lethargy
What 3 clinical pathological changes are seen in melamine and cyanuric acid toxicosis
- hyperkalemia
- hyperphosphatemia
- circular green-brown crystals in urine sediment
Where is pathology of melamine and cyanuric acid toxicosis restricted? What is observed?
kidney
- bilateral renomegaly
- crystals in urine and pale-yellow crystals in renal collecting tubules
- dark red band of hemorrhage at corticomedullary junction
- tubular necrosis and rupture
- interstitial edema and hemorrhage
- increased inflammatory cells
How can melamine-cyanuric acid crystals be observed on histology and urinalysis?
HISTO = oil red O selectively stains melamine-cyanuric acid crystals, but not calcium oxalate or calcium phosphate crystals
URINALYSIS: dissolve over time when kidney secretions are stored in formalin
How is crystalluria in melamine and cyanuric acid toxicosis treated? What can decrease the formation of crystals?
fluid therapy/increased water intake increases urine output and elimination of crystals
alkalinization of urine
