Flashcards in Week 4: Pathology of tubulointerstitial and Cystic renal diseases Deck (27):
Define tubulointerstitial disease. Two principal causes?
-Definition: group of disorders characterized by abnormalities of renal tubules and the interstitial. Can spare the glomueruli.
1. inflammatory mediated injury
-non infectious: interstitial nephritis
2. Ischemic or toxic injury
-acute tubular necrosis
Define pyelonephritis. Etiology? Pathogenesis?
-Definition: an acute suppurative bacterial infection of the kidney. Associated with UTIs.
-bacterial infections caused by colonization of distal urethra and introits by coliform bacteria with adhesions on pili or upward spread by instruments
-most common: E.coli, other gram negative rods from fecal flora-Proteus, Klebsiella, Enterobacter, Strep faecalia, Pseudomonas aeruginosa
-most common mechanism: ascending infection from bladder
-promoted by obstruction, vesicoureteral reflux, or other reason for urinary stasis
-spread by blood less common
Predisposing conditions for pyelonephritis.
-urinary tract obstruction
-instrumentation, e.g. catheters
-females between 1-40, in males, incidence rises with age
-diabetes mellitus-due to impaired leukocyte fxn, frequent micturition (fainting during or after urination), nephrogenic bladder
-immunosuppression and immunodeficiency
Pathology of pyelonephritis
-hallmark: patchy interstitial suppurative inflammation and focal tubular necrosis
-gross: Large kidney, bulging cut surface, yellow streaks of pus, inflamed calyces and pelvis
-micro: PMNs in interstitium and tubules with focal micro-abscesses
Clinical course of pyelonephritis.
-acute onset of chills, fever, dysuria, frequent and urgency with costovertebral angle tenderness and pain
-lab findings: pyruia, WBC casts, pathogenic organisms 10^3 to 10^5 organisms/mL
Complications of acute pyelonephritis
-septicemia and gram negative shock
-papillary necrosis: mainly with DM
-pyonephrosis-pus fills in collecting systems of obstructed hydronephrotic kidney
-perinephric abscess: extension of the inflammatory process outside the renal capsule
Define chronic pyelonephritis.
-chronic tubulointerstitial inflammation and renal scarring with involvement of the calyces and pelvis
-other factors involved in pathogenesis in addition to bacterial infection (e.g. reflux and obstruction)
-chronic tubulointerstitial inflammation with scarring of the renal parenchyma and distortion of the renal calyces and pelvice
Etiology of chronic pyelonephritis
1. chronic obstruction: acute renal infection and inflammation superimposed upon diffuse or localized obstructive lesions-->parenchymal atrophy and extensive scarring
2. Reflux nephropathy: superimposition of urinary infection on congenital vesicoureteral reflex-->scarring
Pathology of chronic pyelonephritis
-gross: irregular discrete corticomedullary scars (pitted), overlaying dilated blunted calyx (fibrosis and shrunken parenchyma)
-micro: patchy atrophic tubules and hypertrophic surviving tubules, dilated with colloid casts (thyroidization), chronic interstitial inflammation, fibrosis
Clinical course of chronic pyelonephritis.
-insidious course, not recognized until onset of renal failure with lassitude, headaches, weight loss, nausea, polyuria, nocturne. HTN and its complications
-Lab findings: bacteriruia >10^5, low grade pyruria, proteinuria, elevated BUN and Cr (evidence of renal failure)
Define xanthogranulomatous pyelonephritis
-distant variant of chronic pyelonephritis
-foamy macrophages mixed with plasma cells, lymphocytes, neutrophils, giant cells
-associated with stag horn calculus with superimposed proteus infection
-yellow orange nodules mistaken for renal carcinoma
Causes of drug induced nephropathy (non infectious interstitial nephritis)
--delayed hypersensitivity reaction due to happen like effect. Onset ~2 weeks after exposure to drug
-penicillins and rifampin
-thiazides and cimetidine
Pathology of drug induced nephropathy
-interstitial edema with lots of eosinophils and neutrophils.
-may be granulomas (methicillin).
-Tubular necrosis and regeneration are present and glomeruli are normal
Clinical course of drug induced nephropathy
-15 days after exposure, prevents with rash, fever, eosinophilia, hematuria, mild proteinuria
-50% have Cr elevation
-acute renal failure may develop
Describe radiation nephritis.
-6-12 months after radiation
-micro: glomeruli hyalinization, severe interstitial fibrosis and tubular atrophy-->HTN, anemia, and proteinuria
Define acute tubular necrosis.
-characterized by destruction of tubular epithelial cells and clinically by suppression of renal function
-most common cause of acute renal failure
-when urine falls below 400mL in 24 hrs
-necrosis from ischemia or toxicity
Pathogenesis of ischemic ATN
-medulla is susceptible to ischemia because it receives small portion of blood fluid
-ischemi-->vasoconstriction-->reduced GFR and oliguria
-clinical complication after shock produced by severe bacterial infection, large burns, mismatched blood transfusion reaction, massive crushing injuries
Pathology of ischemic ATN
-focal tubular necrosis at multiple irregular points
-rupture of BM sometimes
-hyaline and granular casts of Tamm-Horsfall protein (glycoprotein normally secreted by TALH in normal urine)
Etiology of nephrotoxic ATN
-sensitive to toxic injury due to vast electrically charged surface for reabsorption, active transport for ions and organic acids, ability to concentrate urine
-drugs: amphotericin B, gentamicin
Pathology of nephrotoxic ATN
-more diffuse with toxic compared to segmental with ischemic
-greatest injury usually in PT
Pathology of ADPKD
-gross: bilateral, large, polycystic kidneys
-renal cysts vary in size
-often contain colorless fluid/turbid hemorrhagic or gelatinous fluid
-micro: variably sized cysts lined by simple epithelium with normally differentiated intervening parenchyma
Etiology of ARPKD (autosomal recessive polycystic kidney disease or infantile polycystic kidney disease). Prognosis?
-mutation on chromosome 6p (PKHD1). gene encodes fibrocystin, function unknown
-failure to communicate between nephron and pelvicalyceal system
-babies usually don't survive long and older children have associated hepatic fibrosis
Pathology of ARPKD
-gross: bilaterally enlarged, multi cystic kidneys with normal contour. Uniform sized cysts
-micro: cysts lined by uniform cuboidal cells, rare glomeruli but no normal parenchyma
Describe medullary sponge kidney
-congenital disorder with unknown pathogenesis
-renal condition consisting of multiple cystic dilations of the medullary collecting ducts
-usually asymptomatic unless presenting with secondary complication, usually in 40s-60s.
-the dilations give sponge like appearance to renal medulla
Describe uremic medullary cystic disease. Pathology?
-usually originates in childhood but found in adolescents and adults
-progressive renal failure and cyst formation in medullary and cortico-medullary regions of the kidney
-gross: small contracted kidneys, granular surfaces, cysts are present near corticomedullary junction
-micro: cotical tubular atrophy with interstitial fibrosis, cysts lined by flattened or cuboidal cells and border by inflammation or fibrosis
Clinical features of uremic medullary cystic disease
-polyuria, polydipsia -due to defect in concentration ability
-tubular acidosis also prominent
-progression terminal renal failure in 5-10 years
-assoc. with hepatic fibrosis, retinal dysplasia, hyperuricemia, and gouty arthritis