2/18/99
Pathology II
1. inflammatory involvement of tubules and interstitium
2. ischemic or toxic tubular injury
Pyelonephritis—bacterial infections in renal pelvis
Interstitial nephritis—non infectious causes
Acute pyelonephritis
· common suppurative inflammation by bacterial infection
· enteric gram negative rods—
· E. coli—most common
· Proteus, Klebsiella, Enterobacter, Pseudomonas—in recurrent infections
2 Routes
· Hematognous—less common
· Ascending infection—lower urinary tract—most important route
· Colonization of distal urethra and female introitus
· Movement into bladder against urine flow
· Urethral instrumentation: catheterization/cysoscopy
· Female more prone due to short urethra and urethral trauma during sexual intercourse
Bladder Defenses
1. antimicrobial properties of bladder mucosa
2. flushing action w/voiding of urine
Predisposing factors
· obstruction-urinary stasis-leads to bacterial proliferation and ascent to renal pelvis
· more common in patents w/urinary tract incompetence of vesicoureteral orifice
· normal-1 way valve preventing retrograde urine
· flow-incompetent valve allows reflux of urine to bladder
· diabetes
· septicemia
· necrotizing papillitis
Morphology
· suppurative necrosis or abscess formation w/I renal substance
· early stages: limited to interstitial tissue
· later stages: abscess rupture into tubules
· white cell casts: in urine from neutrophils in collecting ducts—Pyelonephritis is the most common disease associated w/ WBC casts
· note: casts form when proteins precipitate and get in the tubular lumina, it is generally held that Tamm-Horsfall mucoproteins from the basic matrix of the all casts. WBC’s enter tubular lumina from the interstitium
Pyelonephrosis-due to obstruction blocking the drainage of suppurative exudate
Necrotizing papillitis or Papillary necrosis-complication more common in diabetes
· pahognomonic feature is sharply defined gray-white to yellow necrosis of the apical 2/3
clinical course
· sudden onset-pain at costovertebral angle
· systemic signs of infection-chills, fever, malaise
· puruia, bacteriuria
· bladder irritation-dysuria, frequency, urgency
· course tends to be self-limiting
· recurrent or chronic if predisposing factors are present
· poor prognosis w/ necrotizing papillitis-sepsis and renal failure
Chronic Pyelonephritis and Reflux Nephropathy
· important cause of chronic renal failure
· interstitial inflammation and scarring of the renal parenchyma w/grossly visible scarring and deformity of the pelvicalyceal system
1. Chronic Obstructive Pyelonephritis
· Recurrent infections due to persistent obstructive lesions-posterior urethral valves, calculi, or obstructive anomalies of the ureter
2. Chronic Reflux Pyelonephritis
· More common forms, recurrent infections and damage due to persistent reflux
Clinical Course
· Present late
· Don’t know what is going on—gradual
· Pyelograms show asymmetrically contracted kidney w/ blunting and deformity of the calyceal system
· Glomerular lesions ultimately develop, eventually leading to renal failure
Interstitial Nephritis
· Due to use of ab and analgesics
· Acute drug-Induced interstitial nephritis
· Adverse reaction-synthetic penicillin's, methicillin, ampicillin, rifampin, diuretics (thiazides, NSAIDS
Clinically
· 15 days (range 2-4days) after exposure
· fever, eosinophilia, skin rash
· renal abnormalities, hematuria, mild proteinuria, leukocyturia
· acute renal failure w/ oliguria (esp. in older patients)
Morphology
· interstitial edema w/ lymphocytes and macrophage infiltration
Pathogenesis
· immune mechanism is probable
· hypersensitivity suggested by latent period, eosinaphilia, skin rash
Analgesic Nephropathy
· patients consume large quantities of analgesics may develop chronic interstitial nephritis, often associated w/renal papillary necrosis
· mixtures of drugs is more common: phenacetin, aspirin, acetaminophen, caffeine, or codeine for long periods
Clinical Features
· chronic renal failure
· hypertension
· anemia
Acute Tubular Necrosis (ATN)
· acute tubular necrosis is a clinicopathlogic entity characterized morphologically by destruction of tubular epithelial cells and clinically by acute suppression of renal fxn
· most common cause of acute renal failure
Clinical Patterns
1. ischemic ATN-inadequate blood flow, hypotension, shock, severe trauma, hemolytic crises, mismatched blood transfusions
2. Nephrotoxic ATN-caused b poisons, heavy metals, e.g. mercury, organic solvents, e.g. carbon tetrachloride, radiographic contrast media
Pathogenesis
· Tubular injury-damage to epithelial cells, debris blocking urine outflow
· Increase in intratubular pressure causes decrease GFR
· Blood flow distrubances-intrarenal vasoconstriction causing decrease GFR and decrease O2
Clinical
· Initiating phase
· Maintenance phase—2-6days. Urine output falls dramatically. Signs of symptoms of fluid overload
· Recovery-steady increase in urine vol., increased vulnerability to infection
Cystic Diseases of the Kidney
· Simple Cysts
· Cortical, 1-5 cm, common post mortem finding
· Differentiate from tumor
Autosomal Dominant (Adult) Polycystic Kidney Disease
· Multiple expanding cysts of both kidneys that destroy parenchyma
· Incidence: 1 in 1000
· 10% of cases of chronic renal failure
Clinical
· no symptoms until 40 y/o
· flank pain-heavy dragging sensation
· excruciating pain w/acute distention of cyst
· intermittent gross hematuia and urinary infection
· hypertension in 75% of patients
· saccular (berry)aneurysms-Circle of Willis-15%-30%
· asymptomatic liver cysts in 1/3rd
· ultimately fatal-end stage renal failure about age 50
· renal transplantation
Urinary Outflow obstruction
Renal Stones
· 75% calcium oxalate or calcium oxalate/calcium phosphate
· 15%-magnesium ammonium phosphate
· 10%-uric acid or cystine
· all stones have an organic matrix of mucoprotein
· the most important cause is increased urine concentration of the stone’s constituents, so that it exceeds their solubility in urine (supersaturtion)
Calcium Stones (Table 14-4)
· 50% of patients have hypercalciuria w/no hypercalcimia
· absorb excessive amounts of calcium form the gut and excrete into the urine. Some have a primary renal defect of calcium reabsorption
· 5-10% have hypercalcemia w/hypercalciuria (hyperparathyroidism, vit D intoxication , sarcoidosis)
· 20% have excessive excretion of uric acid in urine-thought to provide a nidus for calcium deposition
Magnesium ammonium phosphate (struvite) stones
· Alkaline urine-due to urinary tract infections
· Proteus vulgaris and staph are urea-splitting bacteria and predispose to stones
· Bacteria can sever as nidi for any kind of stone
· Avitaminosis A – desquamated squamous from metaplastic epithelium of collecting system
Uric Acid stones (acidic urine)
· gout and diseases involving rapid cell turnover, such as leukemia
· high uric acid levels (hyperuricemia, increased urine urate) and development of stones
· 50% of patients w/ uric acid stones have neither, but a tendency for acid urine (pH<5.5)
Cystine stones (acidic urine)
· genetically determined defect in renal transport of cystine
Morphology
· unilateral in 80% of patients
· common sites-renal pelvis, calyces, bladder
· tend to be small (2-3mm)—smooth or jagged
· Staghorn calculi—cast of renal pelvis and calyceal system. Massive size-magnesium ammonium phosphate
Clinical Course
· Renal pelvis stones-few symptoms or renal damage
· Ureteral passage-intense pain-renal or urethral colic-paroxysms of flank pain radiating toward the groin
· Gross hematuia
· Urinary flow obstruction
Tumors of the Kidney
· Renal cell carcinoma—most common
· Wilm’s tumor—kids
Renal cell Carcinoma
· Adenocarcinoma from tubular epithelial cells
· 80-90% of kidney cancer
· 2% of cancers overall
· men 2;1—ages 60-70
· associated w/ von Heippel-Lindau syndrome (VHL)
Clinical triad
· painless hematuria, long standing fever, dull flank pain
· usually large before detection
· polycythemia in 5-10% (elaboration of erythropoietin by renal tumor)
· metastasis-lungs and bone
Wilm’s Tumor
· major cancer in children—ranks 3rd for <age 10
· may arise sporadically or be familial
· deletion of short arm of chromosome 11 w/loss/mutation of cancer suppressor gene
Bladder Tumors
· most common among these
· cause more deaths than kidney
1. papilloma-rare and benign
2. transitional cell carcinomas-grades I-II-III
· ranges from noninvasive to invasive, well-differentiated to anaplastic
3. squamous cell carcinoma-only 5%
4. in situ
· painless hematuria
· bladder Men 3:1—ages 50-70 yrs
· exposure to beta-naphthylamine—increase50x more common
· cigarette smoking, chronic cystitis, schistosomiasis of bladder, certain drugs (cyclophophamide)
· stubborn