Renal Pathology Flashcards
Casts in urine-presence of casts indicates that hematuria/pyruia are of glomerular or renal origin
bladder cancer, kidney stones–> hematuria, no casts
acute cystitis--> pyuria, no cast
RBC casts
WBC casts
Fatty casts (“oval fat bodies”)
Granular (“muddy brown”) casts
Waxy casts
Hyaline casts
Casts in urine
RBC casts-Glomerulonephritis, hypertensive emergency
WBC casts-Tubulointerstitial inflammation, acute pyelonephritis, transplant rejection.
Fatty casts (“oval fat bodies”)-Nephrotic syndrome. Associated with “Maltese cross” sign.
Granular (“muddy brown”) casts-Acute tubular necrosis (ATN)
Waxy casts-End-stage renal disease/chronic renal failure
Hyaline casts-Nonspecific, can be a normal finding, often seen in concentrated urine samples.
Nomenclature of glomerular disorders
Focal- Characterisitc: < 50% of glomeruli are involved, Example: Focal segmental glomerulosclerosis
Diffuse- Characterisitc: > 50% of glomeruli are involved, Example: Diffuse proliferative glomerulonephritis
Proliferative-Characterisitic: Hypercellular glomeruli, Example: Membranoproliferative glomerulonephritis
Membranous- Characteristic: Thickening of glomerular basement membrane (GBM), Example: Membranous nephropathy
Primary glomerular disease- Characteristic: 1° disease of the kidney specifically impacting the glomeruli, Example: Minimal change disease
Secondary glomerular disease- Characterisitic: Systemic disease or disease of another organ system that also impacts the glomeruli, Example: SLE, diabetic nephropathy
Nephrotic syndrome-
NephrOtic syndrome—massive prOteinuria (> 3.5 g/day) with hypoalbuminemia, resulting edema, hyperlipidemia. Frothy urine with fatty casts.
Disruption of glomerular filtration charge barrier may be 1° (eg, direct sclerosis of podocytes) or 2° (systemic process [eg, diabetes] secondarily damages podocytes).
Severe nephritic syndrome may present with nephrotic syndrome features (nephritic-nephrotic syndrome) if damage to GBM is severe enough to damage charge barrier.
Associated with hypercoagulable state due to antithrombin (AT) III loss in urine and risk of infection (loss of immunoglobulins in urine and soft tissue compromise by edema).
Minimal change disease (lipoid nephrosis)
Focal segmental glomerulosclerosis
Membranous nephropathy
Amyloidosis
Diabetic glomerulonephropathy
Minimal change disease (lipoid nephrosis)-Most common cause of nephrotic syndrome in children.
Often 1° (idiopathic) and may be triggered by recent infection, immunization, immune stimulus. Rarely, may be 2° to lymphoma (eg, cytokine-mediated damage).
1° disease has excellent response to corticosteroids.
LM (light microscopy)—Normal glomeruli (lipid may be seen in PCT cells)
IF (immunofluorescence)—⊝
EM (electron microscopy)—effacement of podocyte foot processes
Focal segmental glomerulosclerosis-Most common cause of nephrotic syndrome in African-Americans and Hispanics.
Can be 1° (idiopathic) or 2° to other conditions (eg, HIV infection, sickle cell disease, heroin abuse, massive obesity, interferon treatment, or congenital malformations).
1° disease has inconsistent response to steroids. May progress to CKD.
LM—segmental sclerosis and hyalinosis
IF—often ⊝ but may be ⊕ for nonspecific focal deposits of IgM, C3, C1
EM—effacement of foot processes similar to minimal change disease
Membranous nephropathy-Also known as membranous glomerulonephritis.
Can be 1° (eg, antibodies to phospholipase A2 receptor) or 2° to drugs (eg, NSAIDs, penicillamine, gold), infections (eg, HBV, HCV, syphilis), SLE, or solid tumors
1° disease has poor response to steroids. May progress to CKD.
LM—diffuse capillary and GBM thickening
IF—granular due to immune complex (IC) deposition
EM—“Spike and dome” appearance of subepithelial deposits
Amyloidosis-Kidney is the most commonly involved organ (systemic amyloidosis). Associated with chronic conditions that predispose to amyloid deposition (eg, AL amyloid, AA amyloid).
LM—Congo red stain shows apple-green birefringence under polarized light due to amyloid deposition in the mesangium
Diabetic glomerulonephropathy-Most common cause of ESRD in the United States.
Hyperglycemia –> nonenzymatic glycation of tissue proteins –> mesangial expansion; GBM thickening and increase permeability. Hyperfiltration (glomerular HTN and increased GFR) –> glomerular hypertrophy and glomerular scarring (glomerulosclerosis) leading to further progression of nephropathy
LM—Mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson lesions, arrows in
Nephritic syndrome-NephrItic syndrome = Inflammatory process.
When glomeruli are involved, leads to hematuria and RBC casts in urine.
Associated with azotemia, oliguria, hypertension (due to salt retention), proteinuria, hypercellular/inflamed glomeruli on biopsy.
Acute poststreptococcal glomerulonephritis
Rapidly progressive (crescentic) glomerulonephritis
Diffuse proliferative glomerulonephritis
IgA nephropathy (Berger disease)
Alport syndrome
Membranoproliferative glomerulonephritis
Acute poststreptococcal glomerulonephritis-Most frequently seen in children. ~ 2–4 weeks after group A streptococcal infection of pharynx or skin. Resolves spontaneously in most children; may progress to renal insufficiency in adults. Type III hypersensitivity reaction.
Presents with _peripheral and periorbital edem_a, cola-colored urine, HTN. ⊕ strep titers/serologies, decreased complement levels (C3) due to consumption.
LM—glomeruli enlarged and hypercellular
IF—(“starry sky”) granular appearance (“lumpy-bumpy”) B due to IgG, IgM, and C3 deposition along GBM and mesangium
EM—subepithelial immune complex (IC) humps
Rapidly progressive (crescentic) glomerulonephritis-Poor prognosis, rapidly deteriorating renal function (days to weeks).
LM—crescent moon shape. Crescents consist of fibrin and plasma proteins (eg, C3b) with glomerular parietal cells, monocytes, macrophages
Several disease processes may result in this pattern which may be delineated via IF pattern.
Linear IF due to antibodies to GBM and alveolar basement membrane: Goodpasture syndrome—hematuria/hemoptysis; type II hypersensitivity reaction;
Treatment: plasmapheresis
Negative IF/Pauci-immune (no Ig/C3 deposition): Granulomatosis with polyangiitis (Wegener)—PR3-ANCA/c-ANCA or Microscopic polyangiitis—MPO-ANCA/p-ANCA
Granular IF—PSGN or DPGN
Diffuse proliferative glomerulonephritis-Often due to SLE (think “wire lupus”). DPGN and MPGN often present as nephrotic syndrome and nephritic syndrome concurrently.
LM—“wire looping” of capillaries
IF—granular;
EM—subendothelial and sometimes intramembranous IgG-based ICs often with C3 deposition
IgA nephropathy (Berger disease)-Episodic hematuria that occurs concurrently with respiratory or GI tract infections (IgA is secreted by mucosal linings). Renal pathology of IgA vasculitis (HSP)
LM—mesangial proliferation
IF—IgA-based IC deposits in mesangium;
EM—mesangial IC deposition
Alport syndrome-Mutation in type IV collagen –> thinning and splitting of glomerular basement membrane. Most commonly X-linked dominant.
Eye problems (eg, retinopathy, lens dislocation), glomerulonephritis, sensorineural deafness;
“can’t see, can’t pee, can’t hear a bee.”
EM—“Basket-weave”
Membranoproliferative glomerulonephritis-MPGN is a nephritic syndrome that often co-presents with nephrotic syndrome.
Type I may be 2° to hepatitis B or C infection. May also be idiopathic.
Subendothelial IC deposits with granular IF
Type II is associated with C3 nephritic factor (IgG antibody that stabilizes C3 convertase –> persistent complement activation –> decreased C3 levels).
Intramembranous deposits, also called dense deposit disease
In both types, mesangial ingrowth –> GBM splitting –> “tram-track” appearance on H&E and PAS stains.
Kidney stones-Can lead to severe complications such as hydronephrosis, pyelonephritis. Obstructed stone presents with unilateral flank tenderness, colicky pain radiating to groin, hematuria. Treat and prevent by encouraging fluid intake.
Most common kidney stone presentation: calcium oxalate stone in patient with hypercalciuria and normocalcemia.
calcium
Ammonium magnesium phosphate
Uric acid
Cystine
calcium: precipitate with: Calcium oxalate: hypocitraturia, Xray: Radiopaque, CT findings: Radiopaque, Urine crystal: Shaped like envelope A or dumbbell,
Notes:Calcium stones most common (80%); calcium oxalate more common than calcium phosphate stones. Hypocitraturia often associated with decreased urine pH.
Can result from ethylene glycol (antifreeze) ingestion, vitamin C abuse, hypocitraturia, malabsorption (eg, Crohn disease). Treatment: thiazides, citrate, low-sodium diet.
calcium-Calcium phosphate: increased pH, xray: Radiopaque, CT findings: Radiopaque, urine crystal: Wedge-shaped prism,
Note: Treatment: low-sodium diet, thiazides.
Ammonium magnesium phosphate-increased pH, xray: Radiopaque, CT findings: Radiopaque, urine crystal: Coffin lid,
notes: Also known as struvite; account for 15% of stones. Caused by infection with urease ⊕ bugs (eg, Proteus mirabilis, Staphylococcus saprophyticus, Klebsiella) that hydrolyze urea to ammonia –> urine alkalinization. Commonly form staghorn calculi C .
Treatment: eradication of underlying infection, surgical removal of stone.
Uric acid-decreased pH, xray: RadiolUcent, CT finding: Minimally visible, urine crystal: Rhomboid D or rosettes,
Notes: About 5% of all stones. Risk factors: decreased urine volume, arid climates, acidic pH. Strong association with hyperuricemia (eg, gout). Often seen in diseases with increased cell turnover (eg, leukemia).
Treatment: alkalinization of urine, allopurinol.
Cystine-decreased pH, xray:Faintly radiopaque, CT Finding: Moderately radiopaque, Urine crystal: Hexagonal,
Notes: Hereditary (autosomal recessive) condition in which Cystine-reabsorbing PCT transporter loses function, causing cystinuria. Transporter defect also results in poor reabsorption of Ornithine, Lysine, Arginine (COLA). Cystine is poorly soluble, thus stones form in urine. Usually begins in childhood. Can form staghorn calculi. Sodium cyanide nitroprusside test ⊕. “SIXtine” stones have SIX sides.
Treatment: low sodium diet, alkalinization of urine, chelating agents if refractory.
Hydronephrosis
Distention/dilation of renal pelvis and calyces A . Usually caused by urinary tract obstruction (eg, renal stones, severe BPH, congenital obstructions, cervical cancer, injury to ureter); other causes include retroperitoneal fibrosis, vesicoureteral reflux. Dilation occurs proximal to site of pathology.
Serum creatinine becomes elevated if obstruction is bilateral or if patient has an obstructed solitary kidney.
Leads to compression and possible atrophy of renal cortex and medulla.
Renal cell carcinoma
Polygonal clear cells A filled with accumulated lipids and carbohydrate. Often golden-yellow B due to increased lipid content
Originates from PCT –> invades renal vein (may develop varicocele if left sided) –> IVC –> hematogenous spread –> metastasis to lung and bone.
Manifests with hematuria, palpable masses, 2° polycythemia, flank pain, fever, weight loss
Treatment: surgery/ablation for localized disease. Immunotherapy (eg, aldesleukin) or targeted therapy for metastatic disease, rarely curative. Resistant to chemotherapy and radiation therapy.
Most common 1° renal malignancy . Most common in men 50–70 years old, increased incidence with smoking and obesity
paraneoplastic syndromes: eg, PTHrP, Ectopic EPO, ACTH, Renin
Associated with gene deletion on chromosome 3 (sporadic, or inherited as von Hippel-Lindau syndrome).
Renal oncocytoma
Benign epithelial cell tumor arising from collecting ducts (well-circumscribed mass with central scar). Large eosinophilic cells with abundant mitochondria without perinuclear clearing
(vs chromophobe renal cell carcinoma). Presents with painless hematuria, flank pain, abdominal mass
Often resected to exclude malignancy (eg, renal cell carcinoma).
Nephroblastoma (Wilms tumor)-Most common renal malignancy of early childhood (ages 2–4). Contains embryonic glomerular structures. Presents with large, palpable, unilateral flank mass and/or hematuria
“Loss of function” mutations of tumor suppressor genes WT1 or WT2 on chromosome 11. May be a part of several syndromes:
WAGR complex: Wilms tumor, Aniridia (absence of iris), Genitourinary malformations, mental Retardation/intellectual disability (WT1 deletion)
Denys-Drash syndrome—Wilms tumor, Diffuse mesangial sclerosis (early-onset nephrotic syndrome), Dysgenesis of gonads (male pseudohermaphroditism), WT1 mutation
Beckwith-Wiedemann syndrome—Wilms tumor, macroglossia, organomegaly, hemihyperplasia (WT2 mutation)
Transitional cell carcinoma
Also known as urothelial carcinoma. Most common tumor of urinary tract system (can occur in renal calyces, renal pelvis, ureters, and bladder) . Can be suggested by painless hematuria (no casts).
Associated with problems in your Pee SAC: Phenacetin, Smoking, Aniline dyes, and Cyclophosphamide.
there is dysplastic urothelium and fibrovascular core in papillary tumor
Squamous cell carcinoma of the bladder
Chronic irritation of urinary bladder –> squamous metaplasia –> dysplasia and squamous cell carcinoma.
Risk factors include Schistosoma haematobium infection (Middle East), chronic cystitis, smoking, chronic nephrolithiasis.
Presents with painless hematuria.
Urinary incontinence
Stress incontinence
Urgency incontinence
Mixed incontinence
Overflow incontinence
Stress incontinence-Outlet incompetence (urethral hypermobility or intrinsic sphincteric deficiency) –> leak with increased intra-abdominal pressure (eg, sneezing, lifting). increased risk with obesity, vaginal delivery, prostate surgery. ⊕ bladder stress test (directly observed leakage from urethra upon coughing or Valsalva maneuver).
Treatment: pelvic floor muscle strengthening (Kegel) exercises, weight loss, pessaries.
Urgency incontinence-Overactive bladder (detrusor instability) –> leak with urge to void immediately. Associated with UTI.
Treatment: Kegel exercises, bladder training (timed voiding, distraction or relaxation techniques), antimuscarinics (eg, oxybutynin)
Mixed incontinence-Features of both stress and urgency incontinence
Overflow incontinence-Incomplete emptying (detrusor underactivity or outlet obstruction) –> leak with overfilling. Associated with polyuria (eg, diabetes), bladder outlet obstruction (eg, BPH), neurogenic bladder (eg, MS). increased post-void residual (urinary retention) on catheterization or ultrasound.
Treatment: catheterization, relieve obstruction (eg, α-blockers for BPH).
Urinary tract infection (acute bacterial cystitis)
Inflammation of urinary bladder.
Presents as suprapubic pain, dysuria, urinary frequency, urgency.
Systemic signs (eg, high fever, chills) are usually absent. Risk factors include female gender (short urethra), sexual intercourse (“honeymoon cystitis”), indwelling catheter, diabetes mellitus, impaired bladder emptying.
Causes:
E coli (most common).
Staphylococcus saprophyticus—seen in sexually active young women (E coli is still more common in this group).
Klebsiella.
Proteus mirabilis—urine has ammonia scent.
Lab findings: ⊕ leukocyte esterase. ⊕ nitrites (indicate gram ⊝ organisms).
Sterile pyuria and ⊝ urine cultures suggest urethritis by Neisseria gonorrhoeae or Chlamydia trachomatis.
Pyelonephritis
Acute pyelonephritis
Chronic pyelonephritis
Acute pyelonephritis-Neutrophils infiltrate renal interstitium A . Affects cortex with relative sparing of glomeruli/vessels.
Presents with fevers, flank pain (costovertebral angle tenderness), nausea/vomiting, chills.
Causes include ascending UTI (E coli is most common), hematogenous spread to kidney. Presents with WBCs in urine +/− WBC casts. CT would show striated parenchymal enhancement B .
Risk factors include indwelling urinary catheter, urinary tract obstruction, vesicoureteral reflux, diabetes mellitus, pregnancy
Complications include chronic pyelonephritis, renal papillary necrosis, perinephric abscess, urosepsis.
Treatment: antibiotics.
Chronic pyelonephritis-The result of recurrent episodes of acute pyelonephritis. Typically requires predisposition to infection such as vesicoureteral reflux or chronically obstructing kidney stones.
Coarse, asymmetric corticomedullary scarring, blunted calyx. Tubules can contain eosinophilic casts resembling thyroid tissue C (thyroidization of kidney).
Xanthogranulomatous pyelonephritis—rare; grossly orange nodules that can mimic tumor nodules; characterized by widespread kidney damage due to granulomatous tissue containing foamy macrophages.
Associated with Proteus infection.
Acute kidney injury
Prerenal azotemia-Due to decreased RBF (eg, hypotension) –> decreased GFR. Na+/H2O and urea retained by kidney in an attempt to conserve volume –> increased BUN/creatinine ratio (urea is reabsorbed, creatinine is not) and decreased FENa.
Intrinsic renal failure-Most commonly due to acute tubular necrosis (from ischemia or toxins); less commonly due to acute glomerulonephritis (eg, RPGN, hemolytic uremic syndrome) or acute interstitial nephritis.
In ATN, patchy necrosis –> debris obstructing tubule and fluid backflow across necrotic tubule –> decrease GFR. Urine has epithelial/granular casts. Urea reabsorption is impaired –> decreased BUN/creatinine ratio and increased FENa
Postrenal azotemia-Due to outflow obstruction (stones, BPH, neoplasia, congenital anomalies).
Develops only with bilateral obstruction or in a solitary kidney.
Postrenal azotemia
in terms of prerenal, intrinsic renal, postrenal
Urine osmolality: > 500, < 350, <350
urina Na: <20, >40, varies
FENa <1%, >2%, varies
Serum BUN/Cr: >20%, <15%, varies
