DISEASES AFFECTING TUBULES AND INTERSTITIUM

Transcription

1 DISEASES AFFECTING TUBULES AND INTERSTITIUM Acute tubular injury (ATI) Pyelonephritis Drug-induced tubulointerstitial nephritis (TIN) Myeloma cast NP Renal stones Urinary outflow obstruction: hydronephrosis

2 ACUTE RENAL FAILURE (ARF) Sudden development of oliguria within 24 hours (less than 400 ml-s of urine) and increasing azotemia (creatinine, BUN)

3 Causes of ARF Prerenal Sustained hypoperfusion of kidneys ischemic ATI Renal Crescentic GN HUS Toxic ATI Acute TIN (infectious, drug-induced, etc.) Postrenal Acute bilateral urinary tract obstruction

4 ACUTE TUBULAR INJURY Morphologically acute tubular injury, clinically acute renal failure are observed Classification Ischemic ATI Nephrotoxic ATI

5 Causes of ischemic ATI Shock Acute pancreatitis-induced hypotension Skeletal muscle injury-induced rhabdomyolysis and myoglobinuria (crush sy in earthquakes; victims have been trapped under fallen masonry)

6 Pathomechanism of GFR and oliguria Intrarenal vasoconstriction ( renin-angiotensin + endothelin + NO + PGI 2 ) and Ischemic tubular injury: epithelial cells detach from the TBM tubular casts obstruction of tubules, in intratubular pressure, backleak of ultrafiltrate to the interstitium oliguria

7 Shock kidney enlarged, swollen kidney (~ 200 g); pale, bloodless cortex, dark medulla

8 ATI: pseudodistal proximal tubuli

9 Eosinophilic granular casts in distal tubules

10 Morphology Gross: Shock kidneys : enlarged, swollen kidneys; pale, bloodless cortex, dark medulla LM: Dilated, pseudodistal proximal tubuli (loss of brush border, simplified wall structure) Detached epithelial cells and granular casts in distal tubuli

11 Nephrotoxic ATI Causes Antibiotics RTG contrast media Poisons excreted by tubular cells: - ethylene glycol - insecticides - certain mushrooms LM Epithelial necrosis in the proximal convoluted and straight tubules and the thick ascending limb

12 Outcome of ATI If the initiating event can be eliminated, and ARF is properly treated, tubular cells regenerate (clinically polyuria) complete recovery

13 ACUTE PYELONEPHRITIS Acute purulent inflammation of the kidney and pelvis induced by Gram-negative bacteria Common Pathogenesis First bacterial cystitis occurs, and bacteria reach the kidney via ascending route

14 Predisposing factors for cystitis Bladder calculi Carcinoma of bladder, carcinoma of cervix invading the bladder Lower urinary tract obstruction (e.g., prostatic hyperplasia) Pregnancy Diabetes Catheterization, cystoscopy

15 Infected urine reaches the kidney(s) via reflux Bacterial cystitis

16 Normal ureteral insertion: acts as a valve that prevents retrograde flow of the urine during micturition. Abnormal ureteral insertion: urine refluxes in the ureter and pelvis during micturition (VUR) May be unilateral or bilateral Kumar et al Pathologic Basis of Disease, 2005.

17 Ascending infection of the kidney Intrarenal reflux From calyces to kidney In the upper and lower poles where papillae have concave area cribrosa Vesicoureteral reflux Congenital: mainly in girls Acquired: prostatic hyperplasia, bladder atony, etc. Infected urine Bacterial cystitis

18 Morphology of acute PN One or both kidneys may be involved LM features: a) patchy interstitial purulent inflammation b) tubular destruction in the involved area c) neutrophilic casts in collecting ducts pyuria Gross: in advanced cases yellowish abscesses in the cortex and medulla, and hyperemia of pelvic mucosa

19 LM: interstitial purulent inflammation, tubular destruction, and neutrophilic casts in collecting ducts

20 Abscesses in the cortex and medulla; the pelvic mucosa is hyperemic

21 Clinical features of acute PN Symptoms of cystitis (lower urinary tract infection): frequency, lower abdominal pain and dysuria (pain or burning on micturition) + renal pain indicating upper urinery tract infection + fever, bacteriuria, and pyuria (granulocytes in the urine) Outcome in uncomplicated cases: proper antibiotic treatment healing

22 Complications Bilateral PN with abscesses ARF and death Perinephric abscess Pyonephrosis (urinary tract obstruction +; pus is unable to pass and thus fills the pelvis, calyces)

23 CHRONIC PYELONEPHRITIS Chronic damage to the pelvis, calyces, and renal interstitium and tubules Frequent

24 Pathomechanism Reflux-induced (scars at the upper and lower poles) Obstruction-induced Superimposed infections enhance scar formation

25 Reflux-induced chronic pyelonephritis leading to kidney shrinkage

26 Coarse scars overlying blunted calyces in reflux-induced PN

27 Chronic pyelonephritis: the papilla is markedly atrophic (arrow), overlaid by corticomedullary scar

28 Gross Dilated, deformed calyces, overlaid by coarse corticomedullary scars LM of scars Interstitial fibrosis with lymphocytic infiltration Atrophic tubules without lumina or with dilated lumina filled with eosinophilic casts ( thyroidization )

29 Thyroidization, interstitial fibrosis

30 Clinical features Can manifest with the symptoms of acute PN Can have a silent, insidious onset, presenting only very late in their course: unilateral shrinkage renal hypertension; bilateral shrinkage (asymmetric involvement on ultrasound evaluation) renal hypertension + renal insufficiency; may lead to ESRD

31 DRUG-INDUCED ACUTE TUBULOINTERSTITIAL NEPHRITIS (TIN) Pathomechanism 2 to 40 days after exposure to antibiotics, nonsteroidal anti-inflammatory drugs, diuretics, etc., hypersensitive inflammatory reaction occurs in the interstitium, damaging the tubules The offending agents act as immunizing haptens Unexpexted event, not related to dose

32 LM: patchy interstitial lymphocytic infiltrates + tubulitis

33 Eosinophils may be present in the infiltrate

34 Clinical features In middle-aged or older individuals Sudden onset of skin rash, hematuria, mild proteinuria, increasing se-creatinine, oliguria, ARF Outcome Withdrawal of the drug, proper treatment of the initiating event and ARF recovery in most of the patients In minority: progression to chr. TIN ESRD

35 Chronic TIN: widespread interstitial fibrosis, tubular atrophy, lymphocytic interstitial infiltrates

36 MYELOMA CAST NEPHROPATHY Tubulointerstitial nephritis in myeloma Pathogenesis The tumorous plasma cells may elaborate only the light chain part of the immunoglobulin molecule (Bence Jones protein) enter into the circulation These molecules pass through the GBM May, however, be nephrotoxic and precipitate in the tubules cast NP

37 Cast NP: precipitated hyaline cast surrounded by multinucleated giant cells; note interstitial fibrosis

38 LM - chronic TIN: interstitial fibrosis, atrophy of tubules, inflammatory giant cell reaction around large, distinctive protein casts

39 Clinical features May cause acute renal failure or chronic renal failure Renal disease may be the first manifestation of myeloma

40 NEPHROLITHIASIS/urolithiasis Stones can arise at any level in the urinary tract, mainly in the pelvis Frequent Men are more affected than women Frequent in white men between ys

41 Composition Majority: Ca-containing stones: Ca-oxalate or Ca-oxalate mixed with Ca-phosphate; can be seen on X-ray Minority: triple (struvite) stones: ammoniummagnesium-ca-phosphate; associated with infection of urea-splitting bacteria that convert urea to ammonia; staghorn calculi

42 Pathogenesis Increased urine concentration of the stone s constituents, so that it exceeds their solubility (supersaturation) Reduced fluid intake for years (1000 ml water instead of 2500 ml) Increased exercise with dehydration Hyperuricemia: precipitated urate salt provide a nidus for calcium deposition

43 Consequences Small stones frequently travel down the ureter: intense colic pain radiating to the ipsilateral testicle or labia majora + ulceration of mucosa hematuria Staghorn stones remain localized but lead to pyelonephritic scars because cause permanent obstruction and predisposes to infection Extracorporeal shock wave lithotripsy uses sound waves to break up large stones so they can more easily pass down the ureters into the bladder.

44 The traveling small stone obstructed the orifice of ureter (arrow); forced drinking of 1.5 liters of fluid the stone passed

45 The sharp edges of the stone incised the urothelium of ureter during the travel hematuria

46 Staghorn calculus: remains localized; leads to pyelonephritic scar

47 Pyelonephritic scar due to stone in the calyx: obstruction + infections are keyplayers in scar formation

48 URINARY TRACT OBSTRUCTION Can occur suddenly or insidiously, and at any level of the urinary tract Can be complete or incomplete Sudden obstruction by calculi, blood clots, sloughed renal papillae colic pain; if treated, structural changes in the kidney do not develop Insidious obstruction hydronephrosis Increased susceptibility to infection and stone formation

49 HYDRONEPHROSIS Dilation of the the pelvis and calyces and atrophy of the kidney caused by subtotal obstruction of the urinary tract Obstruction above the trigone of the urinary bladder unilateral hydronephrosis; below the trigone: bilateral hydronephrosis Causes Pelvis: calculi, cc, cong. ureteropelvic stenosis Ureter: calculi, cc, pregnancy Bladder: calculi, cc, neurogenic bladder Urethra: prostatic hyperplasia, prostatic cc, congenital posterior valve stricture

50 Morphology Gross: Dilation of the renal pelvis and calyces, atrophied papillae, markedly thinned renal parenchyma; depending on the level of obstruction, one or both ureters may be dilated (hydroureter) Superimposed acute pyelonephritis is common pyonephrosis LM: Severe atrophy of medulla and cortex, atrophy and even disappearance of tubuli, interstitial fibrosis, focal interstitial lymphocytic infiltrates in the interstitium + foci of acute pyelonephritis

51 Hydronephrosis: dilated calyces, atrophied papillae (arrows), thinned parenchyma

52 Consequences Unilateral hydronephrosis may remain silent for long periods, since the unaffected kidney maintains adequate renal function Bilateral hydronephrosis: polyuria as a result of defects in tubular concentrating mechanisms, later chronic renal failure, renal hypertension; if obstruction becomes complete: death