Tubulointerstitial Disease Flashcards
causes of acute renal failure
pre-renal
renal (tubular, glomerular, vascular)
post-renal
causes of tubular ARF
- acute tubular injury (ischemic or toxic)
- inflammatory
what nephron segments are the most susceptible to acute tubular injury
PCT and thick ascending loop of Henle
due to HIGH O2 demand
ischemic ATI
decreased perfusion of renal parenchyma caused by vasoconstriction
segmental distribution
what part of the kidney is most susceptible to ischemic ATI
outer medulla
LOW O2 availability
toxic ATI
nephron exposure to endogenous/exogenous toxins
diffuse distribution
what part of the kidney is most susceptible to toxic ATI
renal tubules
high surface area, active transport systems, high O2/energy demands, high toxin exposure
what is the maladaptive response to injury in the nephron
- tubular activation
- histologic cell changes
- cell swelling
- cell detachment
- de-differentiation
- proliferation
- differentiation
tubular activation
increased demand on tubular cells –> release of cytokines –> recruitment of inflammatory cells and fibroblasts –> fibrosis + necrosis –> tubule loss
occurs in response to ischemia/hypoxia, glomerular injury, and tubular injury
what is the main sign of glomerular dysfunction
proteinuria
how is glomerular dysfunction related to tubular injury
glomerular dysfunction causes proteinuria
proteins in urine cause tubular damage –> tubular activation
what histologic changes occur to tubular epithelial cells during maladaptive response to injury
loss of polarity
loss of microvilli/brush border –> decreased absorptive capacity –> high Na in filtrate reaching DCT –> increased vasoconstriction
why do cells start to swell in maladaptive response to injury
leukocyte infiltrate and vesiculation –> increased intracellular pressure
what happens when cells detach from basement membrane
dead tubular cells slough off into lumen –> increase intratubular pressure and decreased GFR –> wrinkled basement membrane (tubular atrophy)
formation of casts –> can obstruct distal tubules
what is de-differentiation
simplification (stretching out) of surviving epithelial cells to cover the exposed segments of the basement membrane; causes cells to become undifferentiated
what is required in order for cells to regenerate
INTACT basement membrane
what happens if the basement membrane is not intact OR cells don’t regenerate
chronic nephron loss –> CKD
what happens once cells completely cover the basement membrane
cells proliferate across the basement membrane and re-differentiation (reestablish polarity)
what are the classes of inflammatory diseases
- tubulointerstitial nephritis
- interstitial nephritis (acute and chronic)
- pyelonephritis (acute and chronic)
what is the pathogenesis of tubulointerstitial nephritis
infectious
sterile (glomerular disease)
idiopathic
chronic
pathogenesis of leptospirosis
- bacteria is shed in urine
- enters through MM or abraded skin
- moves through the blood to the kidney, liver, uterus, and eye and migrates through endothelium
what kind of disease does leptospirosis cause
- interstitial nephritis
- tubulitis
interstitial nephritis
lymphocyte and plasma cell infiltrate/inflammation
tubulitis
neutrophil infiltrate in renal tubules
what is chronic nephritis
loss of nephrons that get replaced by fibrosis
gross and histologic lesion of chronic nephritis
scalloped edges
interstitial inflammation, fibrosis, tubular atrophy w/ intact glomeruli
what is the sign of tubular atrophy
wrinkled basement membrane
what histologic lesion does FIP cause
perivascular pyogranulomatous interstitial nephritis/vasculitis (neutrophils + lymphocytic infiltrate)
causes pressure necrosis –> tubule loss
pyelonephritis
ascending infection from lower urinary tract to kidneys
ONLY infectious etiologies
neutrophilic infiltrate
chronic pyelonephritis gross lesion
pale, fibrotic, irregular margins, irregular renal crest
linear scars from ascending necrosis
mechanism of NSAID toxicity
- NSAIDs inhibit COX 1 and 2
- decreased production of prostaglandins
- decreased vasodilation –> increased vasoconstriction
- vasoconstriction –> medullary ischemia –> renal papillary necrosis
renal papillary necrosis
death of renal parenchyma in the region of the renal papilla
caused by ischemia due to low perfusion of papillary vessels
mechanism of copper toxicity
chronic low-level copper exposure –> massive hepatic copper storage –> stressful event triggers hepatocellular necrosis –> copper releases into the blood –> damages RBCs (intravascular hemolysis) –> anemia + hemoglobinuria –> ischemia + tubular necrosis
occurs in sheep
gross lesion of copper toxicity
gun metal blue kidneys
