Week 4: Pathology of tubulointerstitial and Cystic renal diseases

Question 1

Define tubulointerstitial disease. Two principal causes?

Answer 1

• 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

Question 2

Define pyelonephritis. Etiology? Pathogenesis?

Answer 2

-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

Question 3

Predisposing conditions for pyelonephritis.

Answer 3

• 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

Question 4

Pathology of pyelonephritis

Answer 4

• 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

Question 5

Clinical course of pyelonephritis.

Answer 5

• 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

Question 6

Complications of acute pyelonephritis

Answer 6

• 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

Question 7

Define chronic pyelonephritis.

Answer 7

• 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

Question 8

Etiology of chronic pyelonephritis

Answer 8

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

Question 9

Pathology of chronic pyelonephritis

Answer 9

• 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

Question 10

Clinical course of chronic pyelonephritis.

Answer 10

• 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)

Question 11

Define xanthogranulomatous pyelonephritis

Answer 11

• 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

Question 12

Causes of drug induced nephropathy (non infectious interstitial nephritis)

Answer 12

• -delayed hypersensitivity reaction due to happen like effect. Onset ~2 weeks after exposure to drug
• penicillins and rifampin
• thiazides and cimetidine

Question 13

Pathology of drug induced nephropathy

Answer 13

• interstitial edema with lots of eosinophils and neutrophils.
• may be granulomas (methicillin).
• Tubular necrosis and regeneration are present and glomeruli are normal

Question 14

Clinical course of drug induced nephropathy

Answer 14

• 15 days after exposure, prevents with rash, fever, eosinophilia, hematuria, mild proteinuria
• 50% have Cr elevation
• acute renal failure may develop

Question 15

Describe radiation nephritis.

Answer 15

• 6-12 months after radiation

- micro: glomeruli hyalinization, severe interstitial fibrosis and tubular atrophy–>HTN, anemia, and proteinuria

Question 16

Define acute tubular necrosis.

Answer 16

• 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

Question 17

Pathogenesis of ischemic ATN

Answer 17

• 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

Question 18

Pathology of ischemic ATN

Answer 18

• 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

Question 19

Etiology of nephrotoxic ATN

Answer 19

• 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

Question 20

Pathology of nephrotoxic ATN

Answer 20

• more diffuse with toxic compared to segmental with ischemic
• greatest injury usually in PT

Question 21

Pathology of ADPKD

Answer 21

• 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

Question 22

Etiology of ARPKD (autosomal recessive polycystic kidney disease or infantile polycystic kidney disease). Prognosis?

Answer 22

• 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

Question 23

Pathology of ARPKD

Answer 23

• 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

Question 24

Describe medullary sponge kidney

Answer 24

• 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

Question 25

Describe uremic medullary cystic disease. Pathology?

Answer 25

- 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

Question 26

Clinical features of uremic medullary cystic disease

Answer 26

- 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

Question 27

Describe dialysis cystic disease. Etiology, pathology, clinical course

Answer 27

- 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