Week 4: Pathology of tubulointerstitial and Cystic renal diseases Flashcards
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 - infectious
- 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.
ETIOLOGY
-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
PATHOGENESIS
-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
- vesicoureteral reflex
- pregnancy
- 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
- preterm labor
- 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
- chronic obstruction: acute renal infection and inflammation superimposed upon diffuse or localized obstructive lesions–>parenchymal atrophy and extensive scarring
- 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
- reversible
- 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)
- pigment casts
- glomeruli spared
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
- ethylene glycol
- drugs: amphotericin B, gentamicin
- metals
- radiocontrast media
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
- sodium wasting
- tubular acidosis also prominent
- progression terminal renal failure in 5-10 years
- assoc. with hepatic fibrosis, retinal dysplasia, hyperuricemia, and gouty arthritis
Describe dialysis cystic disease. Etiology, pathology, clinical course
- definition: cortical or medullary cysts occurring in patients with end-stage renal disease who have undergone prolonged dialysis
- etiology: may be result of fibrosis than dialysis
- gross: cysts containing clear fluid and some times calcium oxalate crystals
- micrl: cysts lined by flattened epithelium, but foci of papillary hyperplasia of the tubular lumen are common
- increased incidence of renal adenoma and renal cell carcinoma arising within the wall of cysts
