11. Path of Tubular and Interstitial Diseases Flashcards
what is osmotic nephrosis? is it reversible? when is it often seen?
reversible renal tubular injury, often seen following administration of agents used to induce osmotic diuresis. considered a hydropic change (swelling, taking up of fluid)
what are the agents that can induce osmotic diuresis (leads to osmotic nephrosis)?
hypertonic agents like sucrose, mannitol, dextran, IV contrast material.
where in the kidney is osmotic nephrosis most pronounced?
prox convoluted tubules
what is the histo appearance of osmotic nephrosis?
prox tubules look pale and foamy due to accumulation of vacuoles, which distend the cytoplasm of epithelial cells. the cavuoles are distended phagolysosomes.
what is hyaline droplet change? is it reversible?
protein resorption droplets in the proximal tubular epithelial cells. reversible.
what does hyaline droplet change look like on histo?
cytoplasm of the prox tubules is finaly granular, due to accumulation of resorbed droplets of protein.
what causes hyaline droplet change? what will reverse it?
excessive protein in the tubules. seen in nephrotic patients. will disappear with the reduction of proteinuria. droplets themselves are not problematic.
what is acute kidney injury? what are the 2 most common types?
acute injury of the renal tubules that results in acute renal failure (ARF).
subtypes of AKI: ischemic, toxic.
what labs define acute renal failure (ARF)?
- acute drop in GFR
- oliguria/anuria (<400ml/24hrs)
- elevated BUN and serum creatinine
what are the 3 general types of ARF?
pre-renal
post-renal
intra-renal (interstitial, tubular most common)
ischemic AKI: when does it most often occur? reversible?
in the setting of inadequate visceral blood flow. usually with hypotension/shock. reversible
ischemic AKI: what problems are seen clinically?
- decreased Na, Cl and fluid reabsorption (elevated urine Na)
- impaired ability to concentrate urine
how can AKI lead to ARF? what is the critical event?
tubular necrosis with reduction in GFR leading to elevated BUN and serum creatinine.
what are some postulated mechanisms for how ischemic AKI leads to ARF?
overall picture: reduced GFR. possible mechs:
- backleak of filtered fluid through damaged tubule wall -> incr pressure from the outside -> collapse -> decr GFR
- tubular obstruction by casts and necrotic cells -> incr tubular lumen pressure -> decr GFR
- arteriolar vasoconstriction due to secondary to activation of RAAS (tubulo-glomerular feedback) -> decr GFR
ischemic AKI: gross appearance? what regions are most affected? what is the pattern of pathology?
swollen kidney with pale cortex, congested medulla. blood has redistributed from cortex to medulla. pattern of ischemia tends to be patchy and multifocal.
affects the prox tubule and the ascending/thick LOH.
toxic AKI: as compared to ischemic AKI, what regions are most affected? what is the pattern of pathology?
mostly prox convoluted tubule affected. tends to be more diffuse (less patchy) involvement
ischemic AKI: microscopic appearance?
simplification/distalization of the prox tubules: cells are dilated, flattened, have lost brush border, lost their integrity, disintegrated. many tubules contain epithelial cells that are sloughed off. hard to distinguish from toxic AKI via microscopic view
acute tubular necrosis: part of what process? appearance on path?
- part of ischemic or toxic acute kidney injury. -epithelial lining of tubule is disrupted, cells dislodged, sloughing into lumen. may also be flattened.
- may be clumps of necrotic, shrunken sloughed cells forming a luminal cast
- may be mitotic activity indicating regeneration.
renal infarct: part of what process? reversible? appearance on gross, appearance on histo?
extreme ischemic AKI. not reversible.
will see massive areas of yellowish/pale infarcts.
-cytoplasm of epithelial cells is intact but pale. no nuclei. capillaries congested with blood.
Toxic AKI: why is the tubular epithelium vulnerable to toxins?
- high proportion of cardiac output directed to kidney
- high concentration of toxins
- high rate of energy consumption in order to reabsorb, actively transport, concentrate urine.
what are the types of toxins that may cause acute tubular necrosis via toxic AKI?
antibiotics, solvents, metals, other….
toxic AKI: what is path appearance?
tubules are diffusely hypereosinophilic, epithelial cells are sloughing into the tubular lumens. extensive loss of epithelial cell nuclei.
clinical course of AKI/ATN: what are three phases? what occurs in each?
- initiating phase. 1-2 days. mild decr in urine output.
- maintenance phase. significant drop in urine output. salt and water overload. elevated BUN and K. metabolic acidosis.
- Recover phase. increasing urine output, decr K, BUN, creatinine.
define tubulointerstitial diseases
varied group of inflammatory diseases, involving tubules and interstitium with diverse causes and pathogenic mechanisms.
AKI/ATN: what is overall clinical picture?
Acute necrosis without inflammation.
what are some clinical manifestations that relate primarily to defects in tubular function?
- decr concentration –> polyuria
- decr salt reab -> Na wasting
- decr acid excretion -> metabolic acidosis
what are the two major disease categories of tubulointerstitial diseases?
- pyelonephritis (infection related)
- tubulo-interstitial nephritis (IgE reaction to drug/toxin)
what is pyelonephritis (in english)? what are the 2 categories of pyelonephritis?
kidney infection.
acute, chronic
what are the most common etiologies of pyelonephritis?
gram neg bacilli (e coli, proteus, klebsiella, enterobacter).
pyelonephritis: what are the 2 main types of pathogenesis?
hematogenous, ascending
ascending pyelonephritis: typical sequence?
- colonisation of distal urethra
- introduction into the bladder
- incompetence of the vesico-ureteral orifice, (anatomic) leading to reflux
incompetence of the vesico-ureteral orifice - wtf?
normally the ureter enters the bladder tangentially. when bladder contracts, it compresses the intramural part of the ureter, reducing reflux. most patients with urinary reflux have abnormal anatomy of this junction, more of a perpendicular entrance of the ureter. allows reflux.
predisposing conditions for pyelonephritis?
urinary obstruction, catheterization, vesico-ureteral reflux, pregnancy, sex, age, diabetes, immunosuppression
ascending infection: what is pattern in kidney?
ascending infection tends to occur in poles (due to slightly different anatomy of calyces: complex papillae rather than simple papillae).
hematogenous infection: what is the pattern in kidney?
arrives from aorta, miliary distribution of punctate microabscesses on all surfaces/areas of the kidney.
ascending pyelonephritis: gross appearance?
streaky pale yellow material, corresponding to linear purulent inflammation.
hematogenous pyelonephritis: microscopic appearance?
inflammatory focus w PMNs, both within tubules and within interstitium.
ascending pyelonephritis: microscopic appearance?
PMNs with vaguely streak-like distribution, roughly aligned with parallel to collecting ducts
the three main complications of acute pyelonephritis?
Papillary necrosis
pyonephrosis
perinephric abscess
what is papillary necrosis? what condition is it a complication of?
necrosis of tip of medullary pyramid. pale, necrotic medulla, intense inflammation present in adjacent parenchyma. complication of acute pyelonephritis
what is pyonephrosis? what condition is it a complication of?
kidney filled with pus. will see dilatation of the pelves, rims of yellowish discoloration in remaining parencyma. may see embedded calculus. complication of acute pyelonephritis
what is perinephric abscess? what condition is it a complication of?
an infection of the pelvis that has ruptured through the pelvic wall. complication of acute pyelonephritis
what the scarring pattern from acute pyelonephritis look like?
classically, broad based and U-shaped (as opposed to the V shaped from ischemia/infarct). more common in upper and lower poles
what is chronic pyelonephritis?
tubulointerstitial inflammation and scarring, associated with pathologic involvement of calyces and pelvis
chronic pyelonephritis: pathological appearance?
nonspecific: have to find scarring, inflammation in association with deformed calyx. cannot dx by light microscopy alone.
besides infection, what else can cause tubulointerstitial nephritis?
allergic response to drugs, toxins
drug/toxin induced tubulointerstitial nephritis: most frequently seen with what? what are clinical signs?
seen with penicillins, antibiotics, diuretics, NSAIDS.
clinical sx: fever, eosinophilia, rash. acute renal failure with oliguria in 50%
immune-mediated tubulointerstitial nephritis: what is cause?
late-phase IgE mediated hypersensitivity reaction.
immune-mediated tubulointerstitial nephritis: what cells respond?
T helper lymphocytes, macrophages. hallmark are eosinophils.
immune-mediated tubulointerstitial nephritis: what is pathogenic sequence?
drug acts as a hapten secreted by the tubule. covalently binds to a tubular cell component which then becomes immunogenic. IgE and immune reactions attack!
immune-mediated tubulointerstitial nephritis: what is seen on histo?
scattered, patchy infiltrate of lymphocytes in the interstitium. presence of eosinophils.
analgesic abuse nephropathy: pathology?
tubulo-interstitial nephritis and fibrosis, papillary necrosis, urothelial carcinoma
urate nephropathy: three types?
- acute uric acid nephropathy
- chronic urate nephropathy
- nephrolithiasis
what is acute uric acid nephropathy? it occurs typically in what patients?
caused by precipitation of uric acid crystals in collecting ducts, -> obstruction -> acute renal failure.
particularly in cancer patients following chemotherapy.
what is chronic urate nephropathy? occurs in what patients?
tophus formations (deposits of urate crystals). occurs in patients with hyperuricemia
what is nephrolithaisis? occurs in what patients?
urate stones. 22% of patients with gout
urate nephropathy: what is appearance on micro and path?
several presentations, but common features are crystals/deposits/stones. obstruction.
what is myeloma kidney?
cause of renal dysfunction in pts with multiple myeloma. Bence-Jones light chains cause proteinuria. toxicity to tubular epithelial cells, cast formation leads to luminal obstruction.
