Renal Pathology - Tubular Disease Flashcards
What are 4 common causes of tubular diseases?
tubular epithelium damage from:
1. blood-borne infections (septicemia)
2. toxins and chemicals
3. hypoxia/ischemia
4. ascending infection from the lower urinary tract (pyelonephritis)
What is the most important cause of acute renal failure? What are 2 causes? 2 results?
acute tubular necrosis
nephrotoxins or ischemia
oliguria and anuria
How can the cause of acute tubular necrosis be differentiated?
- NEPHROTOXINS: causes necrosis, but leaves the basement membrane intact, so that the damaged epithelium is regenerated
- ISCHEMIA: results in damage to the basement membrane so the tubular damage heals by fibrosis
Toxic vs. ischemic acute tubular necrosis, histology:
TOXIC: necrotic cells in lumen with intact BM
ISCHEMIC: necrosis of everything with BM rupture
What are 3 reasons that toxins preferably damage kidneys?
- 25% of cardiac output goes to the kidney
- substance is filtered into the urine by the glomerulus
- toxin or its metabolites within the renal tubular lumina are concentrated
What are 9 common nephrotoxins of domestic animals?
- PIGMENTS: hemoglobin, myoglobin, bile/bilirubin
- HEAVY METALS: lead, mercury
- PHARMACEUTICALS: aminoglycosides, NSAIDs
- FUNGAL TOXINS: Aspergillus and Penicillium ochratoxin
- PLANT TOXINS: pigweed, oxalate-containing plants, oak tannins
- ANTIFREEZE: ethylene glycol
- VITAMINS and MINERALS: vitamin D, hypercalcemia
- BACTERIAL TOXINS: epsilon toxin from Clostridium
- PET FOOD CONTAMINANTS: melamine, cyanuric acid, raisins, grapes
What is hemoglobinuric nephrosis? What does this cause?
increased hemoglobin in urine/kidney
intravascular hemolysis —> hemoglobinemia —> hemoglobin passes into the glomerular filtrate —> intraluminal accumulation —> direct damage to tubular epithelium and hypoxia —> necrosis of epithelium and hemoglobin cast formation
What are specific causes of hemoglobinuric nephrosis in sheep, cattle, horses, and dogs?
SHEEP: chronic copper toxicity
CATTLE: leptospirosis, babesiosis, Clostridium haemolyticum
HORSES: red maple toxicity
DOGS: babesiosis or autoimmune hemolytic anemia
How does the kidney look grossly with hemoglobinuric nephrosis?
diffuse red-brown to blue-black discoloration due to hemoglobin in urine
(chronic copper toxicity, sheep)
What is seen histologically in hemoglobinuric nephrosis?
coagulative necrosis of tubular epithelium with orange-red, granular hemoglobin casts in lumen
Hemoglobinuric nephrosis:
- immune-mediated hemolytic anemia in dogs + pre-hepatic icterus
- red maple toxicosis in horses
What is the cause of myoglobinuric nephrosis? What is the mechanism of disease?
acute and extensive muscle necrosis
increased myoglobin in the urine is filtered by the glomerulus and is toxic to the tubular epithelium
What are specific causes of myogloninuric nephrosis in horses, greyhounds, and wild/exotic animals and cattle? What is an additional cause?
- exertional rhabdomyolysis, capture myopathy
- Cassia spp. toxicity (plant causes muscle necrosis)
- severe direct trauma to muscle (traffic accident)
How does myoglobinuric nephrosis look grossly? Histologically?
diffuse myoglobin staining of the cortex and medullar (red-brown)
intraluminal myoglobin casts —> necropsy needed for differentiation from hemoglobinuria
What causes cholemic nephrosis? How does this affect the kidney?
acute fulminant hepatic failure —> icterus —> bile cast nephropathy
green discoloration
How can animals come into contact with lead and develop heavy metal poisoning? What does this cause?
old paints, batteries, automobile components
damages membranes of epithelial cells and mitochondria, with the deposition of acid-fast positive intranuclear inclusion bodies composed of lead-protein complexes
What is ethylene glycol? How does this cause renal damage?
constituent of engine antifreeze solution that is sweet and commonly voluntarily consumed by young animals
oxidized by alcohol dehydrogenase in the liver into toxic metabolites, glycoaldehyde, glycolic acid, glyoxylate, and oxalate and is filtered by the glomerulus, causing direct toxic effects (ATP depletion, membrane damage)
What is characteristic of ethylene glycol toxicity?
proximal tubular degeneration and necrosis and calcium oxalate crystals that are birefringent with polarized light arranged in rosettes or sheaves
(large amount = pathognomonic)
What did old-school veterinarians used to give animals that have consumed antifreeze?
ethanol - competes with ethylene glycol for alcohol dehydrogenase
What are 4 common causes of ischemic renal tubular damage?
(anything that will decrease the volume of blood going through the kidneys)
1. volume depletion - vomiting, diarrhea, GI hemorrhage, burns
2. not enough blood being pumped - heart failure, severe valvular disease
3. systemic vasodilation/hypotension - sepsis, massive release of cytokines
4. renal arterial occlusion - thrombi, infarction
What are renal infarcts? What causes them? What are 4 predisposing conditions?
localized areas of coagulative necrosis
obstructive materials and decrease blood supply: thrombi (hypercoagulable state), septic emboli, neoplastic emboli
- valvular endocarditis
- feline cardiomyopathy (HCM)
- endotoxemia
- neoplasia
What are 3 common predilection sited for renal infarction?
- RENAL ARTERY: entire kidney will be necrotic; rare
- ARCUATE ARTERY: wedge-shaped necrosis of cortex and medulla
- INTERLOBULAR ARTERY: necrosis of cortex only
How do renal infarcts progress?
- acute, early = swollen, dark red
- 2-3 days = pale, surrounded by thin zone of hyperemia (degradation of Hb)
- chronic = pale, shrunken, and depressed due to loss of tissue and replacement by fibrosis
What is the cause of renal medullary/papillary/crest necrosis? What are 4 examples?
ISCHEMIA
- NSAIDs - block prostaglandin production (blocks COX1 and COX2), which control local blood supply, leading to ischemia of the medulla and necrosis
- medullary amyloidosis - compresses medullary capillaries
- chronic pyelonephritis - scarring, connective tissue compresses medullary capillaries
- pelvic calculi/tumor - pressure necrosis
What are 2 common things that medullary renal necrosis and NSAIDs are associated with?
- dehydration
- analgesic nephropathy - dehydrated horse treated with phenylbutazone