Term
| How does tubular injury decrease GFR? |
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Definition
1. Tubuloglomerular feedback via the macula densa (increased Na+ because tubular cells aren't able to reabsorb it results in decreased renin release, which decreases ATII and thus blood pressure and GFR.)
2. Increased tubular pressure due to casts and/or crystals
3. Increased permeability of tubules leads to leakage of filtrate into interstitium and thence to blood. |
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Term
| What drugs cause tubular injury via ischemia? |
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Definition
-NSAIDs: inhibition of vasodilatory prostacyclin in the medulla causes medullary and papillary ischemia.
-Cisplatin: induces renal vasoconstriction; may have direct toxicity to tubules as well. |
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Term
| What drug causes tubular injury via increased membrane permeability? |
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Definition
| Amphotericin B (antifungal) |
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Term
| Which drugs/metabolites cause tubular injury via intratubular crystal formation? |
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Definition
-Melamine/cyanuric acid
-Uric acid (from purine catabolism): in Dalmatians
-Cysteine: genetic inability to metabolize (several breeds of dog)
-Ethylene glycol |
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Term
| How do aminoglycosides damage tubular cells? |
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Definition
| Freely filtered; in tubular epithelial cells induce lysosomal damage. Exact mechanism unknown. |
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Term
| How do mycotoxins (e.g. fumonisin B) cause tubular damage? |
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Definition
| Interferes with sphingolipids in tubular cells...exact mechanism unknown. |
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Term
| How do hemoglobin and myoglobin cause tubular damage? |
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Definition
| Iron is directly toxic by generation of reactive oxygen species. Pigment casts can obstruct tubules. |
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Term
| How do heavy metals (esp. metal salts) cause tubular damage? |
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Definition
| Bind to sulfhydryl groups on proteins and inhibit critical cellular functions. |
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Term
| WHat is Fanconi syndrome? |
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Definition
| Tubules fail to reabsorb glucose, amino acids, Na+, PO4---, and HCO3-. Inherited in Basenjis and can be acquired with Cu+ toxicity. |
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Term
| Can damaged tubules regenerate? |
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Definition
| Yes, if the insult is not catastrophic (i.e. if there are at least some intact epithelial cells left). Nearby intact cells "de-differentiate" so they can proliferate, migrate, and mature to cover for sloughed epithelium. |
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Term
| How long does it take for tubular epithelium to begin to regenerate? |
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Definition
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Term
| What is the most common cause of glomerular disease? |
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Definition
| Immune-mediated mechanisms (immune complexes recruit inflammatory cells which induce damage via cell-, complement-, and cytokine-mediated pathways). Damage is to podocytes, basement membranes, and/or endothelium causing less selective filtration. |
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Term
| What is the most common basement membrane component affected to cause glomerular dysfunction? |
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Definition
| Collagen Type IV. Results in increased permeability. |
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Term
| What is a non-inflammatory cause of glomerular damage? |
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Definition
| Amyloid deposition. This can be associated with chronic systemic inflammation, though. |
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Term
| Over time, glomerular disease always leads to _____ and ______ GFR. |
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Definition
| Sclerosis, decreased GFR. |
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Term
| What are some infectious diseases that result in antigen-antibody complex deposition in the glomerulus? |
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Definition
| Lyme disease, Canine adenovirus, FIP, FIV, equine infectious anemia. |
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Term
| Where are 2 places in the kidney that amyloid can be deposited? |
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Definition
1. Glomerulus (most common in dogs, cattle).
2. Medulla (Sharpeis, cats) -> may not be proteinuria in these animals. |
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Term
| WHat is hemolytic uremic syndrome? |
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Definition
| Due to Shiga toxin (E. coli and other bacteria) causing endothelial damage leading to ischemia + necrosis. |
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Term
| What effect can disseminated bacterial infection have on the kidneys? |
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Definition
| Bacterial emboli can lodge in the glomerular tufts, leading to microthrombi and/or neutrophilic inflammation. |
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Term
| What is hereditary glomerulopathy of Finnish-Landrace sheep? |
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Definition
| Decreased complement factor (C3) results in decreased clearance of immune complexes -> membranoproliferative glomerulonephritis. |
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Term
| What 3 viral infections of pigs cause kidney damage? |
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Definition
| Classical Swine fever, African swine fever, Porcine circovirus. Cause necrotizing vasculitis, glomerulitis, and/or thrombosis. |
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