JPC SYSTEMIC PATHOLOGY
Signalment (JPC # 1947999): Hampshire ewe
HISTORY: This tissue is from a 4-year-old Hampshire ewe that became ill 36 hours after initial access to a new field. Clinical signs included salivation, mydriasis, tremors, ataxia, and paresis.
HISTOPATHOLOGIC DESCRIPTION: Kidney: Multifocally and predominantly within the cortex, tubules are ectatic, expanded up to 4 times normal, and lined by epithelium that is either attenuated, degenerative (characterized by pale, vacuolated cytoplasm), necrotic (characterized by fragmented, hypereosinophilic cytoplasm and pyknosis), or regenerative (characterized by increased mitotic activity and large pale basophilic nuclei with a high nuclear to cytoplasmic ratio and piling up of epithelium). Tubules often contain intraluminal yellow, translucent, variably shaped, angular, prismatic, anisotropic crystals; rare small amounts of eosinophilic amorphous material (protein); rare sloughed epithelial cells; or, intensely basophilic acellular, fragmented material (mineral). The interstitium and perivascular connective tissue are mildly expanded by eosinophilic amorphous fluid (edema), eosinophilic beaded to fibrillar material (fibrin) and mild hemorrhage admixed with low numbers of neutrophils, lymphocytes and plasma cells.
MORPHOLOGIC DIAGNOSIS: Kidney, tubules: Degeneration and necrosis, diffuse, moderate with marked tubular ectasia and numerous intratubular oxalate crystals, breed unspecified, ovine.
ETIOLOGIC DIAGNOSIS: Oxalate nephrosis
- Oxalate toxicosis in ruminants occurs primarily from ingestion of plants that contain toxic amounts of soluble oxalate salts
- Oxalate content is highest in the leaves, with lesser amounts in the seeds, and the lowest concentrations in the stems; concentration varies with season and is highest in the autumn (Northern Hemisphere); adaptation to oxalate with chronic exposure to low doses occurs
- Small numbers of oxalate crystals are found occasionally in the renal tubules of many species and are usually an insignificant finding as oxalates are also produced endogenously in the normal degradation of glycine, an important constituent amino acid of collagen and elastin
- Common plants that contain large amounts of soluble oxalates:
- Plants of lesser importance that contain soluble oxalates:
- In ruminants, three events may occur following oxalate ingestion:
- Degradation and detoxification of oxalate by rumen microorganisms into carbonate and bicarbonate (adaptation occurs over 3-5 days as the microorganisms proliferate)
- Oxalate binds to free calcium in the rumen with excretion in feces
- Absorption of oxalate into the blood; binds to circulating calcium and forms insoluble calcium oxalate; may lead to: hypocalcemia, tetany, decreased milk production
- Reabsorption of water in renal tubules -> calcium oxalate crystallization -> tubular obstruction -> acute renal failure
- Calcium oxalate crystal precipitation occasionally observed in vessel lumina or walls causing necrosis and hemorrhage
- Aspergillus genera of fungi may produce abundant oxalates on feedstuffs
- Primary hyperoxaluria: inherited condition that may occur in cats, dogs (Tibetan spaniel, Shih Tzu) and beefmaster cattle
- Pyridoxine (vitamin B6) deficiency and methoxyflurane anesthesia ma also cause renal accumulation of oxalates
TYPICAL CLINICAL FINDINGS:
- May occur as early as 2-4 hours after ingestion
- Depression, anorexia, mild colic, slight to moderate bloating, weakness, restlessness, frequent attempts to urinate, hypocalcemic seizures, coma, and death
- Serum chemistry: Hypocalcemia, hyperphosphatemia, hyponatremia, and hyperkalemia; elevations in BUN, creatinine, ALT, AST, LDH; and metabolic acidosis
- Urinalysis: Calcium oxalate crystalluria; proteinuria
TYPICAL GROSS FINDINGS:
- Pale, edematous, swollen kidneys with yellow streaks in the cortex
- Thin renal medulla with dilated renal calyces that contain numerous small, hard, pale yellow, granular to jagged calculi
- Ascites and hydrothorax; GI tract hemorrhage; epi- and endocardial hemorrhages; rumen edema
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Distension of cortical and medullary tubules with numerous small to large, clear, angular, prismatic, birefringent crystalline deposits or casts; crystals also occasionally in tubular epithelial cells
- Multifocal tubular degeneration and regeneration; occasional lymphoplasmacytic interstitial nephritis and interstitial fibrosis
- Minimal glomerular lesions
- Crystals occasionally present around cerebral, heart, and lung vasculature
- May see prominent oxalosis in the kidneys of aborted bovine fetuses secondary to maternal intake (plants or moldy feed)
- Few oxalate crystals are often seen in degenerate tubule in any species and are generally considered insignificant
- Causes of tubular nephrosis in ruminants:
- Hemoglobinuric or myoglobinuric nephrosis: Tubular lumina with orange-red, granular, refractile material; brown cortex with red-brown streaks in medulla
- Acute toxic nephrosis:
- Heavy metals: Arsenic, lead, cadmium, natural gas condensate
- Pharmaceutic agents: Aminoglycosides
- Plants: Amaranthus retroflexus (pigweed), Quercus (oak tree)
- Vitamin D nephropathy: Prolonged ingestion of plants with vitamin D-like biologic activity (Cestrum diurnum, Solanum malacoxylon, Trisetum flavescens and Meticago sativa); chronic process; calcification of tubular basement membranes, tubular dilation and atrophy; interstitial fibrosis; chalky calcific deposits in cortex
- Horses: Resistant to oxalate nephrosis; succumb to acute gastroenteritis if large amounts of oxalate is ingested
- Dogs, cats, humans, and poultry: Commonly poisoned by ingesting ethylene glycol.
- Outbreaks of melamine associated renal failure also reported in dogs and cats due to contamination of commercial pet food; melamine alone is not toxic but forms insoluble crystals when combined with cyanuric acid which may be mistaken for oxalate crystals
- Captive cheetahs: should be considered as a potential cause of acute renal failure in young captive cheetahs, predisposition is at this time unknown
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- Speight KN, Boardman W, Breed WG, et al. Pathological features of oxalate nephrosis in a population of koalas (Phascolarctos cinereus) in South Australia. Veterinary Pathology. 2012;50(2):299-307.