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interstitial nephritis
RPM I
27
Medical
Graduate
05/05/2010

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Term
what is acute tubular interstitial nephritis?
Definition
an inflammatory lesion of the kidney marked by intense accumulation of PMNs, eosinophils, and lymphocytes induced by immunologic injury (often accompanied by rash/fever - can be due to drugs)
Term
what is chronic tubular interstitial nephritis?
Definition
a fibrosis of the renal tubulointerstitium from immunologic or toxic injury (usually has to do with impairment of blood flow for long periods of time - mostly caused by ischemic events)
Term
what are ddxs when considering acute tubulointerstitial nephritis?
Definition
acute tubular necrosis (ATN - ischemic/toxic) or acute glomerulonephritis
Term
what are the causes of acute renal failure and their associated prevalence?
Definition
ATN (45%, ischemic event causing cells to necrose, not necessarily inflammatory), prerenal (21%, kidney is getting less bloodflow and it thus lowers GFR), acute on chronic renal failure (13%, mostly due to ATN and prerenal disease), urinary tract obstruction (10%, think about this w/sudden deterioration of kidney function - check w/ultrasound, happens w/prostate), glomerulonephritis/vasculitis (4%, post-strep, wegners, goodpastures - see lots of glomerular bleeding), and finally acute interstitial nephritis (2% - uncommon)
Term
what is the pathophysiology of renal injury in acute tubular necrosis?
Definition
intact tubular epithelium -> loss of polarity, tight junction integrity, cell-substrate adhesion, simplification of the brush border -> cell death (necrosis/apoptosis) -> sloughing of viable/nonviable cells w/intraluminal cell-cell adhesion -> cast formation/tubular obstruction
Term
what is seen histologically with acute tubular necrosis?
Definition
necrosis and cell sloughing in the tubulointerstitium. denuding of the GBM
Term
how does acute tubulointerstitial nephritis appear histologically?
Definition
the capillary loop is clear, but the interstitium is filled with inflammatory cells. the chronic is scarred in these areas where inflammatory cells were. (think of it as a rash in the kidney)
Term
what is the most important cause of acute tubulointerstitial nephritis?
Definition
drugs, which can form neoantigens: complex of drugs and cell proteins, which mimics antigens in the kidney - which induces an inflammatory allergic response. NSAIDs, including selective COX-2 inhibitors. PCN (including ceph). rifampin. sulfa drugs. cipro, other quinolongs. cimetidine. allopurinol. proton pump inhibitors. 5-aminosalicylates.
Term
what is the only way to be sure that a pt has acute tubulointerstitial nephritis? how is a clinical dx made?
Definition
renal bx - however most of the time this is not realistic to do, given the precarious health of most pts suspected of this. therefore if a pt has severe hypotension, was just put on PCN, a day later, kidney function deteriorates, they get fever, rash, eosinophila - acute tubulointerstitial nephritis is the clinical dx.
Term
what is the most important infection that can lead to acute tubulointerstitial nephritis? other infections?
Definition
most important: legionella, which is a common cause of pneumonia (accompanied by acute renal failure). leptospirosis, CMV (in immune compromised pts), strep, etc
Term
can autoimmune diseases lead to acute tubulointerstitial nephritis?
Definition
yes - sarcoid (usually seen with respiratory issues) can affect the kidneys, also tubulointerstitial nephrotis and uveitis
Term
what is the clinical presentation of acute tubulointerstitial nephritis?
Definition
urinalysis: pyuria, eosinophila (inflammation - this is a very useful determinant). renal function: acute rise in BUN, creatinine. systemic: fever, rash, malaise.
Term
what is tx for acute tubulointerstitial nephritis?
Definition
remove inciting agent, monitor and consider anti-inflammatories or immunosuppressives (steroids can be very helpful)
Term
how is chronic tubulointerstitial nephritis separated from acute tubulointerstitial nephritis?
Definition
the chronic is not inflammatory, rather it is mainly an ischemic process
Term
what is the spectrum of pathologic findings in chronic renal failure?
Definition
chronic interstitial nephritis: 75% (HTN, chronic ischemia - DM, toxic nephropathies - lead), glomerulonephritis: 15%. cystic disease: 10%
Term
what is thyroidization of the kidney?
Definition
a name for the histologic appearance of chronic fibrosing tububulointerstitial nephropathy - large dilated tubules w/colloid material in them, also scarring
Term
how does chronic tubulointerstitial nephritis associate with renal failure in general?
Definition
chronic tubulointerstitial nephritis as a pathologic entity is a final common pathway for a number of, if not all, disorders causing renal failure. however, it may represent a specific series of disorders originating with a toxic, metabolic, or immune injury to the renal tubules and interstitium
Term
what is the mechanism of renal fibrosis?
Definition
tubular injury leading to recruitment/activation of fibroblasts and epithelial-mesenchymal transformation (tubular cells transforming into fibroblasts)
Term
what is the how is the kidney affected clinically by chronic tubulointerstitial nephritis?
Definition
declining GFR, loss of tubular functions. decreased NH4 (ammonia) production: acidosis. decreased EPO: anemia. disordered medulla: polyuria. decreased vit D activation: osteodystrophy.
Term
what the clinical presentation of chronic tubulointerstitial nephritis?
Definition
slowly developing uremia, minimal proteinuria (glomeruli can be intact, mainly involves interstitium), HTN (due to RAA activation), and chronic anemia
Term
what are the main causes for chronic tubulointerstitial nephritis?
Definition
chronic reflux nephropathy (defect in ability to empty bladders), heavy metal poisoning, analgesic abuse, chronic ischemic nephropathy, and the final common pathway for ESRD etiologies (DM, HTN, chronic hypoxia/ischemia)
Term
do UTIs/pyelonephritis cause chronic tubulointerstitial nephritis?
Definition
no, as long as there is no obstruction or foreign bodies
Term
what is an important cause of chronic renal failure?
Definition
cystic diseases (10% of pts in dialysis units) such as adult polycystic kidney disease (PKD)
Term
what is the etiology of PKD?
Definition
it has a genetic locus - chr 16 + 2 other loci. there is an association with genes for cilia, which are important mechanotransducers. the theory is that every cell has this genetic defect, however not every cell develops into a cyst - therefore it is a 2-hit disease dependent on other mutations. these pts are at risk of developing problems with cilia systemically, aneurysms are a risk - particularly in the brain
Term
what is the pathogenesis of PKD?
Definition
altered tubular development, altered cellular development, altered membrane protein insertion -> all due to crowding from cysts
Term
what is the pathogenesis of analgesic abuse leading to nephropathy?
Definition
no proteinuria (glomerulus normal), bland urinalysis, and renal biopsy showed chronic fibrosis (looked like ischemic effect in interstitium), necrosis of the papilla (very bottom part of the kidney that empties into the calyx) - ultimately the papilla slip out and deposit in the collecting system (looked like stones)
Term
what is the problem with chronic interstitial nephritis tx?
Definition
nothing works once the disease is present
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