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Kidney and Urinary Tract Pathology

Congenital
Horseshoe kidney
o Conjoined at lower pole in lower abdomen
o Inferior mesenteric artery
Renal agenesis
o Absent kidney(s)
Unilateral hypertrophy hyperfiltration renal failure
Bilateral oligohydramnios lung hypoplasia, flat face w/
low set ears, extremity defects (Potter) death
Dysplastic kidney
o Noninherited
o Cysts, cartilage
o Usually unilateral
PKD
o Inherited
o Bilat enlarged kidneys w/ cysts in cortex and medulla
o AR
Infants potter sequence
Congenital hepatic fibrosis portal hypertension, hepatic
cysts
o AD
Young adults
APKD1/2
Berry aneurysm, hepatic cysts, mitral valve prolapse
Medullary cystic kidney disease
o Inherited AD
o Cysts in medullary collecting ducts
o Shrunken kidneys

Acute renal failure


Azotemia incr BUN and Cr w/ oliguria
Prerenal decr blood flow to kidneys (cardiac failure)
o Decr GFR
o Bun:Cr >15
o FENa <1% (tubules intact)
o Urine osm >500 mOsm/kg
Postrenal azotemia obstruction of urinary tract (ureters)
o Decr GFR
o Early BUN/Cr >15
o FENa <1%
o Urine osm >50 mOsm/kg
o Long-standing obstruction tubular damage
BUN:Cr <15
FENa >2%
Urine osm <500 mOsm/kg (inability to concentrate urine)
Acute tubular necrosis intrarenal azotemia
o Brown granular casts plug tubules decr GFR
o BUN:Cr <15
o FENa >2%
o Urine osm <500 mOsm/kg (inability to concentrate urine)
o Hyperkalemia
o Time for recovery tubular cells (stable) need to reenter cell cycle
to regenerate
o Etiology
Ischemia
Preceded by prerenal azotemia
Proximal tubule, medullary segment of thick
ascending limn esp susceptible
Nephrotoxic
Proximal tubule susceptible
Aminoglycosides, heavy metals (Pb), myoglobinuria
(crush injury to muscle), ethylene glycol (oxalate
crystals in urine), radiocontrast dye, urate (tumor lysis
syndrome)
Hydration and allopurinol before chemo to decr urate-
ATN
Acute interstitial nephritis
o Drug-induced hypersensitivity
o NSAIDS, penicillin, diuretics
o Eosinophilia
o Resolve w/ cessation of drug
Renal papillary necrosis
o Flank pain, gross hematuria
o Caused by chronic analgesic abuse (aspirin, phenacetin), DM, sicle
cell, pyelonephritis

Nephrotic syndrome
Proteinuria (>3.5 g/day)
o Hypoalbuminemia pitting edema
o Hypogammaglobulinemia incr infection
o Hypercoagulable state loss of ATIII
o Hyperlipidemia and hypercholesterolemia fatty casts
Minimal change disease
o Most common in children
o Normal glomeruli
o Effacement of foot processes
o Selective proteinuria (albumin, not Ig)
o Excellent response to steroids (damage by cytokines from T cells)
Focal segmental glomerulosclerosis
o Hispanics, African americans
o HIV, heroin, sickle cell
o Effacement of foot processes
o Poor response to steroids chronic renal failure
Membranous nephropathy
o Caucasians
o Hep B/C, solid tumors, SLE, drugs (NSAIDs, penicillamine)
o Thick glomerular basement membrane
o Subepithelial immune complex (granular IF) deposition w/ spike
and dome appearance
Membranoproliferative glomerulonephritis
o Thick glomerular basement membrane
o Tram track appearance
o Immune complex deposition
Type I subendothelial; HBV/HCV
Type II (dense deposit disease) intramembranous; C3
nephritic factor (autoAb stabilizes C3 convertase)
complement overactivation, low C3
o Poor response to steroids chronic renal failure
DM
o High serum glucose nonenzymatic glycosylation of BM
hyaline arteriolosclerosis
o Efferent arteriole constriction high GFR microalbuminuria
nephrotic syndrome
ACE inhibitors slow hyperfiltration damage
o Sclerosis of mesangium Kimmelstiel-Wilson nodules
Systemic amyloidosis
o Amyloid in mesangium
o Apple-green birefringence under polarized light w/ Congo red
staining

Nephritic syndrome
Inflammation and bleeding
Limited proteinuria
RBC casts and RBCs in urine
Hypercellular inflamed glomeruli
Immune complex deposition complement
o C5a neutrophils damage
PSGN
o Group A beta-hemolytic streptococcal infection of skin (impetigo) or
pharynx
o M protein virulence factor
o Presents 2-3 weeks after infection
o Hypercellular inflamed glomeruli
o Subepithelial immune complexes (granular IF)
o Treatment is supportive
Rapidly progressive glomerulonephritis
o Crescents in Bowman space fibrin and macrophages
o Linear IF
Anti-GBM Ab
Against collagen in glomerular and alveolar BMs
Goodpasture syndrome
Hematuria and hemoptysis
Young adult males
o Granular IF (immune complex deposition)
PSGN
Diffuse proliferative glomerulonephritis
Subendothelial
Most common renal disease in SLE
o Negative IF (pauci immune)
Wegener granulomatosis
C-ANCA
Microscopic polyangiitis
P-ANCA
Churg-Strauss
P-ANCA
Granulomatous inflammation, eosinophilia, asthma
IgA nephropathy
o IgA in mesangium
o Hematuria w/ RBC casts following mucosal infections
(gastroenteritis)
Alport syndrome
o X-linked
o Type IV collagen
o Thinning and splitting of GBM
o Hematuria, sensory hearing loss, ocular disturbances

Urinary tract infections


Infection of urethra, bladder, kidney
Ascending infection
Incr in females
Sexual intercourse, urinary stasis, catheters causes
Cystitis bladder infection
o Suprapubic pain
o Fever absent
o Cloudy urine w/ >10 WBCs/hpf
o Positive leukocyte esterase (pyuria) and nitrites
o Culture - >100,000 cfus (gold std)
o Etiology
E coli
Staph saprophyticus incr in young sexually active females
Klebsiella pneumonia
Proteus mirabilis alkaline urine w/ ammonia scent
Enterococcus faecalis
o Sterile pyuria (neg urine culture)
Urethritis due to Chlamydia trachomatis or Neisseria
gonnorhoeae dysuria
Pyelonephritis kidney infection
o Ascending infection
o Vesicoureteral reflux
o Fever, flank pain, WBC casts, leukocytosis
o Causes
E coli
Enterococcus faecalis
Klebsiella
Chronic pyelonephritis
o Interstitial fibrosis and atrophy of tubules
o Vesicoureteral reflux (children) (scarring at upper and lower poles)
or obstruction (BPH, cervical carcinoma)
o Cortical scarring w/ blunted calyces
o Eosinophilic proteinaceous material resembles thyroid follicles
(thyroidization of kidney)
Waxy casts in urine

Nephrolithiasis
Urinary solute as stone
High concentration of solute in urinary filtrate, low urine volume
Hematuria and unilateral flank tenderness
Calcium oxalate/phosphate stones
o Most common
o Hypercalciuria
o Crohn disease
o Trt HCTZ
Ammonium Mg Phos
o Second most common
o Urease positive organisms infection
Proteus, Klebsiella
Alkaline urine stone formation
o Staghorn calculi
o Trt surgical removal and antibiotics
Uric acid
o Radiolucent
o Hot arid climates, low urine volume, acidic pH
o Gout, hyperuricemia in leukemia or myeloproliferative disorders
o Trt hydration and alkalinization of urine (potassium bicarb)
o Allopurinol gout pts
Cysteine
o Children
o Cystinuria decr reabsorption of cysteine
o Staghorn calculi sometimes
o Trt hydration and alkalinization of urine

Chronic renal failure


End stage renal failure
Assoc w/ DM, HTN, glomerular disease
Uremia incr nitrogenous waste inblood (azotemia)
o Urea crystals in skin
Salt and water retention HTN
Hyperkalemia w/ metabolic acidosis
Anemia decr EPO
Hypocalcemia decr 1-alpha-hydroxylation fo vit D by proximal renal
tubule cells and hyperphosphatemia
Renal osteodystrophy secondary hyperparathyroidism, osteomalacia,
osteoporosis
Trt dialysis, renal transplant
o Cysts develop w/in shrunken end stage kidneys during dialysis
incr risk for renal cell carcinoma

Renal neoplasia
Angiomyolipioma
o Hamartoma blood vessels, smooth muscle, adipose tissue
o Incr frequency in tuberous sclerosis
Renal cell carcinoma
o Malignant epithelial tumor from tubules
o Hematuria, palpable mass, flank pain
Paraneoplastic (EPO, renin, PTHrP, ACTH)
Left sided varicocele
o Yellow mass
o Clear cell cytoplasm
o VHL (3p) tumor suppressor gene incr IGF-1 (promotes growth)
and incr HIF txn factor (incr VEGF and PDGF)
o Hereditary or sporadic
Sporadic adult males; single tumor in upper pole of kidney;
smoking risk factor
Hereditary young adults; bilateral
Von Hippel Lindau disease AD disorder assoc w/
inactivation of VHL incr risk fo hemangioblastoma
of cerebellum and renal cell carcinoma
Wilms tumor
o Malignant kidney tumor comprised of blastema (immature kidney
mesenchyme), primitive glomeruli, tubules, stromal cells
Most common malignant tumor in children 3 yrs old avg
o Large unilateral flank mass w/ hematuria and HTN (renin secretion)
o Most sporadic
WAGR syndrome wilms tumor, aniridia, genital
abnormalities, mental/motor retardation; deletion of WT1
tumor suppressor gene (11p13)
Denys-Drash syndrome wilms tumor, progressive renal
disease, male pseudohermaphroditism, WT1 mutations
Beckwith-Wiedemann syndrome wilms tumor, neonatal
hypoglycemia, muscle hemihypertrophy, organomegaly (incl
tongue), WT2 mutations (11p15.5

Lower urinary tract carcinoma


Urothelial (transitional cell) carcinoma
o Malignant tumor arising from urothelial lining of renal pelvis, ureter,
bladder, urethra
Usually bladder
o Risk factor cigarette smoke, naphthylamine, azo dyes,
cyclophosphamide/phenacetin use
o Painless hematuria
o Pathways
Flat high grade flat tumor invades; p53 mutations
Papillary low grade papillary tumor high grade papillary
tumor invasion
o Multifocal and recur (field defect)
Squamous cell carcinoma
o Malignant, usually in bladder
o Squamous metaplasia (bladder not normally lined w/ squamous
epithelium)
o Risk factors chronic cystitis, schistosoma haematobium infection
(Egyptian male), long standing nephrolithiasis
Adenocarcinoma
o Malignant proliferation of glands, usually bladder
o Arises from urachal remnant, cystitis glanduralis, exstrophy

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