Tubulointerstitial Disorders, B&B Flashcards
what cellular changes occur in ischemic acute tubular necrosis (ATN)?
ischemia —> vasoconstriction —> decreased GFR
loss of tubular cell polarity - Na/K ATPase moves to luminal side —> more sodium in urine
[ischemia tends to affect PCT and TAL]
what are some toxin/drug causes of acute tubular necrosis? (name a few)
- aminoglycosides, vancomycin
- iodinated contrast dye
- urine acid (tumor lysis syndrome)
- myoglobin (rhabdomyolysis)
- lead
- cisplatin
- ethylene glycol (antifreeze)
[toxins tend to affect proximal tubule]
describe the pathology of acute tubular necrosis (ATN)
ATN: sudden damage to tubular epithelial cells (patchy/focal necrosis) —> slough off into urine and obstruct flow —> intrinsic renal failure (low GFR, high BUN/Cr)
epithelial cells form granular casts in tubules —> “muddy brown” casts
which portions of the nephron are typically affected by acute tubular necrosis (ATN) caused by ischemia vs toxins?
ischemic ATN affects PCT and TAL
toxic ATN affects PCT only
what are the 3 phases of acute tubular necrosis?
- injury: slight decline in urine output, rising BUN/Cr and declining GFR
- maintenance: oliguria (Na+/H2O overload), hyperkalemia, AG metabolic acidosis
- recovery: polyuria, risk of hypokalemia
what is the usual cause of acute interstitial nephritis?
acute interstitial nephritis: inflammation of renal tubules and interstitium, allergic hypersensitivity reaction mediated by eosinophils and neutrophils —> renal failure
usually triggered by drugs, sometimes infections / autoimmunity or obstruction (crystals, light chains)
usually resolves with removal of trigger (rarely progresses to papillary necrosis)
which classes of drugs are know to cause acute interstitial nephritis? (5, name a few)
acute interstitial nephritis: allergic hypersensitivity reaction mediated by eosinophils and neutrophils
drugs (75% cases) act as haptens:
- sulfonamides (TMP-SMX)
- rifampin
- penicillins/ cephalosporins
- diuretics
- NSAIDs
what are the classic findings of acute interstitial nephritis?
acute interstitial nephritis: allergic hypersensitivity reaction mediated by eosinophils and neutrophils, usually triggers by drugs acting as haptens
—> fever/rash/malaise, acute renal failure (high BUN/Cr), WBC casts, “sterile pyuria” (no bacteria), peripheral eosinophilia, urine eosinophils
how is chronic interstitial nephritis characterized? what is the usual trigger?
mononuclear cell infiltration, fibrosis and atrophy of tubules, mild BUN/Cr elevation, resolves with stoppage of drugs
usually triggered by chronic NSAIDs use or unrecognized acute interstitial nephritis
clinical findings reflect tubule dysfunction - Fanconi syndrome (PCT dysfunction), Type IV (hyperkalemic) RTA, nephrogenic diabetes insipidus
Pt is a 36yo F with PMH of sickle cell anemia presenting with painless gross hematuria. Renal function is normal and there are no WBC casts in the urine. Pt reports urine output is less than normal. What may be going on?
papillary necrosis: coagulative necrosis of renal papillae, causing sloughing of tissue and gross hematuria (often painless)
in isolation - no intrinsic renal failure or WBC casts, urine flow may be obstructed
classic causes include: chronic phenacetin use, diabetes, acute pyelonephritis, sickle cell anemia
in which patients is renal cortical necrosis most likely to be seen?
cortical necrosis: caused by ischemia of renal cortex, acute onset of severe renal failure and oliguria —> anuria
seen in very sick patients with septic shock or obstetric catastrophes
acute interstitial nephritis is likely caused by what type of hypersensitivity reaction?
Type IV (delayed) hypersensitivity - T cell mediated
how can tumor lysis syndrome cause acute kidney injury?
tumor lysis syndrome: cellular breakdown following chemotherapy, basically cells spill their insides
—> hyperphosphatemia (—> hypocalcemia)
—> hyperkalemia
—> hyperuricemia —> uric acid crystals precipitate in distal tubule —> obstruction decreases GFR which induces vasoconstriction —> reduced glomerular blood flow
describe how light chain cast nephropathy occurs
free light chains (kappa, delta) are filtered at the glomerulus and pass to renal tubules —> acute tubule obstruction —> decreased GFR induces vasoconstriction, which decreases blood flow
*problem in conditions like multiple myeloma !
intact antibodies are too big to pass through filter and are excluded from the urine
how does acute vs chronic lead nephropathy manifest?
acute lead nephropathy —> Fanconi’s syndrome (dysfunctional PCT)
chronic lead nephropathy —> HTN, ”Saturnine” gout, tubule atrophy, fibrosis
