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
Crest necrosis, dog with amyloidosis:
Papillary necrosis, dehydrated horse treated with phenylbutazone:
What is the most common cause of inflammatory tubulointersitial disease? How does this occur? What are 2 types?
bacterial/viral septicemia that is able to bypass the glomeruli
infect kidney tubules and damage them —> incites an inflammatory response in the interstitium
1. ACUTE: neutrophils, edema, tubular necrosis; Leptospira spp., canine adenovirus, herpesvirus
2. CHRONIC: mononuclear inflammatory cells, interstitial fibrosis, tubular atrophy/dilation; Leptospira spp., E. coli in cattle, Malignant Catarrhal Fever from BHV-2
What is inflammatory tubulointerstitial disease clinical characterized by?
loss of concentrating ability —> isosthenuria (dilute urine)
What are the 2 classifications of inflammatory tubulointerstitial disease?
- NONSUPPERATIVEL lymphocytes, plasma cells, macrophages
- SUPPURATIVE: neutrophils; embolic, pyelonephritis
What are 7 common causes of nonsuppurative interstitial nephritis?
- Leptospirosis
- white-spotted kidneys in calves (E.coli, salmonella)
- larval migration of Toxocara canis
- malignant catarrhal fever
- FIP
- Lyme disease
- hairy vetch
What does hairy vetch (Vicia spp.) ingestion result in?
nonsuppurative intersitial nephritis with systemic granulomatous inflammation in the skin, heart, spleen, kidney, liver, and intestines
Nonsuppurative interstitial nephritis:
lymphoplasmacytic inflammation
Nonsuppurative interstitial nephritis:
interstitial fibrosis with tubular dilation and atrophy
(Trichrome stain)
What does the random distribution of abscesses point toward?
hematogenous spread
What are white spotted kidneys commonly the result of? How do acute and chronic cases present?
usually an incidental finding in young calves with bacteremia due to E. coli or Salmonella infection
ACUTE: microabscesses
CHRONIC: nonsuppurative interstitial nephritis
Chronic white spotted kidneys, calves:
nonsuppurative interstitial nephritis
- small foci
What causes malignant catarrhal fever in cows? How does this affect the kidney?
BHV2
- nonsuppurative interstitial nephritis
- red, hematogenous kidney
How does hairy vetch (Vicia spp.) toxicity affect bovine kidneys? In what region is this commonly a problem?
- nonsuppurative interstitial nephritis
- pallor cortex
TX and OK
How does Toxocara canis affect the kidneys?
- nonsuppurative interstitial nephritis
- multiple subcapsular, cortical, tan, raised granulomas
(typically an incidental finding)
How does FIP affect the kidneys?
- nonsuppurative interstitial nephritis
- vasculitis centered at veins
- raised, white, granulomatous plaques
What is the most common cause of acute nonsuppurative interstitial nephritis in neonatal puppies? How does the kidney look grossly?
canine herpesvirus-1
multifocal cortical hemorrhages due to viral-induced tubular necrosis and interstitial hemorrhage
What are 4 common causes of suppurative embolic nephritis? What are the 2 common sources?
- Actinobacillus equuli - foals
- Erysipelothrix rhusiopathiae - pigs
- Trueperella pyogenes - cattle
- Corynebacterium pseudotuberculosis - sheep/goats
- septic omphalophlebitis
- septic endocarditis
How does suppurative embolic nephritis present grossly and histologically?
GROSS: multiple, small, randomly scattered microabscesses
HISTO: microabscesses with bacteria
What is pyelonephritis? What is the cause?
inflammation of the renal pelvis and renal parenchyma
ascending urinary tract infection from inhabitants of the vulva, vagina, and prepuce
- E. coli, Pseudomonas spp., Proteus spp., Streptococcus spp.
- Corynebacterium renale in ruminants
- Actinobaculum suis in pigs
What are 4 predisposing factors to pyelonephritis?
- urinary obstruction
- urolithiasis
- prostatic hyperplasia
- transitional cell carcinoma of the urinary bladder
How are bacteria able to reach the renal pelvis to cause pyelonephritis?
- abnormal vesicoureteral reflux
- reverse peristalsis
Suppurative pyelonephritis:
centered in the pelvis + scattered in the cortex
- ascension
What is a common sequelae to pyelonephritis?
pyelonephrosis - compression atrophy of parenchyma caused by purulent accumulation and dilation
This renal tissue was obtained from a horse. Is this normal?
YES - horses have many mucoid cells around the kidneys
What is hydronephrosis? What does this result in? What is the most common cause?
progressive cystic dilatation of renal pelvis from obstruction of urine outflow
pressure atrophy of renal medulla and cortex
obstruction of LUT by calculi, external pressure in the abdomen, or neoplasia in the urinary bladder
What are 4 common species causing parasitic disease in the kidneys?
- Toxocara canis
- Stephanurus denatus (kidney worm) in pigs
- Dioctophyma renale (giant worm) in dogs
- Halicephalobus gingivalis in horses
Stephanurus dentatus:
kidney worm in pigs
Dioctophyma renale:
giant worm in dogs - compresses pelvis causing the kidney to become a fibrous capsule
Halicephalobus gingivalis:
horses
- tumor-like
- granulomatous inflammation
What are the 3 types of primary neoplasms affecting the kidneys? Are they usually unilateral or bilateral?
- epithelial
- embryonal
- mesenchymal
unilateral (<5% bilateral)
- most renal neoplasms are metastatic
What is the most common primary neoplasm of dogs, cattle, and horses? What is its origin? Where does it typically invade?
renal carcinoma
epithelium of proximal tubules
LOCAL: epaxial muscles, adrenal glands, vena cava
SYSTEMIC: lungs, lymph nodes, liver
What is renal cystadenocarcinoma-nodular dermatofibrosis syndrome? What dogs have a high predilection?
bilateral and multifocal renal cystadenoma/carcinoma with nodular dermatofibrosis and uterine leiomyoma commonly seen in German Shepherds
What is nephroblastoma?
the most common primary renal neoplasm of young pigs and chickens originating from metanephric blastema
Where are ectopic nephroblastomas?
embryonal renal tissue becomes trapped between the dura matter and spinal cord, typically at the thoracolumbar junction (T13/L1) in young dogs, which can cause hindlimb paresis
What are 3 other non-epithelial renal neoplasms?
- fibroma, fibrosarcoma - mesenchymal
- hemangiosarcoma - primary or metastatic
- lymphoma - usually bilateral (BLV and cats!)
Metastatic hemangiosarcoma:
Multicentric lymphoma:
common in cattle with BLV
