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FA Renal-Path

Terms in this set (55)

Distal renal tubular acidosis (type 1)
Urine pH > 5.5. Defect in ability of α intercalated cells to secrete H+ no new HCO3− is generated metabolic acidosis.

Associated with hypokalemia, risk for calcium phosphate kidney stones (due to urine pH and bone turnover).


Causes: amphotericin B toxicity, analgesic nephropathy, congenital anomalies (obstruction) of urinary tract.



Renal tubular acidosis-A disorder of the renal tubules that leads to normal anion gap (hyperchloremic) metabolic acidosis.
Proximal renal tubular acidosis (type 2)
Urine pH < 5.5. Defect in PCT HCO3− reabsorption inc excretion of HCO3− in urine and subsequent metabolic acidosis.

Urine is acidified by α-intercalated cells in collecting tubule. Associated with hypokalemia, risk for hypophosphatemic rickets.

Causes: Fanconi syndrome and carbonic anhydrase inhibitors.
Hyperkalemic renal tubular acidosis (type 4)
Urine pH < 5.5. Hypoaldosteronism hyperkalemia NH3 synthesis in PCT NH4+ excretion.

Causes: aldosterone production (eg, diabetic hyporeninism, ACE inhibitors, ARBs, NSAIDs, heparin, cyclosporine, adrenal insufficiency) or aldosterone resistance (eg, K+-sparing diuretics, nephropathy due to obstruction, TMP/SMX).
Casts in urine
Presence of casts indicates that hematuria/pyuria is of glomerular or renal tubular origin. Bladder cancer, kidney stones hematuria, no casts.
Acute cystitis pyuria, no casts
RBC casts
Glomerulonephritis, malignant hypertension.
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
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
nephrotic syndrome
Nephritic syndrome
nephrotic, nephritic syndrome
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.
Acute poststreptococcal glomerulonephritis
LM—glomeruli enlarged and hypercellular A . 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.

Most frequently seen in children. Occurs ∼ 2-4 weeks after group A streptococcal infection of pharynx or skin.

Resolves spontaneously. Type III hypersensitivity reaction.

Presents with peripheral and periorbital edema, cola-colored urine, hypertension.
Positive strep titers/serologies, complement levels (C3) due to consumption.
Rapidly progressive (crescentic) glomerulonephritis
LM and IF—crescent moon shape C . Crescents consist of fibrin and plasma proteins (eg, C3b) with glomerular parietal cells, monocytes, macrophages.

Several disease processes may result in this pattern, in particular:

Goodpasture syndrome—type II
hypersensitivity reaction; antibodies to GBM and alveolar basement membrane linear IF

Granulomatosis with polyangiitis (Wegener) Microscopic Polyangiitis

Poor prognosis. Rapidly deteriorating renal function (days to weeks).
Hematuria/hemoptysis.

Treatment: emergent plasmapheresis.
PR3-ANCA/c-ANCA. Pauci-immune (no Ig/C3 deposition).
MPO-ANCA/p-ANCA. Pauci-immune (no Ig/C3 deposition).
Diffuse proliferative glomerulonephritis
Often due to SLE or membranoproliferative glomerulonephritis.
LM—"wire looping" of capillaries. EM—subendothelial and sometimes
intramembranous IgG-based ICs often with
C3 deposition. IF—granular.

A common cause of death in SLE (think "wire lupus"). DPGN and MPGN often present as nephrotic syndrome and nephritic syndrome concurrently.
IgA nephropathy (Berger disease)
LM—mesangial proliferation.
EM—mesangial IC deposits.
IF—IgA-based IC deposits in mesangium. Renal pathology of Henoch-Schönlein purpura.


Episodic gross hematuria that occurs concurrently with respiratory or GI tract infections (IgA is secreted by mucosal linings). Not to be confused with Buerger disease (thromboangiitis obliterans
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."
"Basket-weave" appearance on EM.
Membrano- proliferative glomerulonephritis
Type I—subendothelial immune complex (IC) deposits with granular IF; "tram-track" appearance on PAS stain D and H&E stain
E duetoGBMsplittingcausedbymesangial ingrowth.

Type II—also called dense deposit disease.

MPGN is a nephritic syndrome that often copresents with nephrotic syndrome.

Type I may be 2° to hepatitis B or C infection. Mayalsobeidiopathic.

Type II is associated with C3 nephritic factor (IgG antibody that stabilizes C3 convertase persistent complement activation C3 levels).
Nephrotic syndrome
NephrOtic syndrome—massive prOteinuria (> 3.5 g/day) with hypoalbuminemia, resulting
edema, hyperlipidemia. Frothy urine with fatty casts.

Due to podocyte damage disrupting glomerular filtration charge barrier. May be 1° (eg, direct sclerosis of podocytes) or 2° (systemic process [eg, diabetes] secondarily damages podocytes). Associated with hypercoagulable state (eg, thromboembolism) due to antithrombin (AT) III loss in urine and risk of infection (due to loss of immunoglobulins in urine and soft tissue compromise by edema).

Severe nephritic syndrome may present with nephrotic syndrome features (nephritic-nephrotic syndrome) if damage to GBM is severe enough to damage charge barrier.
Minimal change disease (lipoid nephrosis
LM—normal glomeruli (lipid may be seen in PCT cells).
IF ⊝.
EM—effacement of foot processes A

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.
Focal segmental glomerulosclerosis
LM—segmental sclerosis and hyalinosis B . IF—often ⊝, but may be ⊕ for nonspecific focal
deposits of IgM, C3, C1. EM—effacement of foot process similar to
minimal change disease

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, chronic kidney disease due to congenital malformations).

1° disease has inconsistent response to steroids. May progress to chronic renal disease.
Membranous nephropathy (membranous glomerulonephritis)
LM—diffuse capillary and GBM thickening C . IF—granular as a result of immune complex deposition. Nephrotic presentation of SLE.
EM—"spike and dome" appearance with subepithelial deposits.

Most common cause of 1° nephrotic syndrome in Caucasian adults. 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 chronic renal disease.
Amyloidosis
LM—Congo red stain shows apple-green birefringence under polarized light due to amyloid deposition in the mesangium.

Kidney is the most commonly involved organ (systemic amyloidosis). Associated with chronic conditions that predispose to amyloid deposition (eg, AL amyloid, AA amyloid).
Diabetic glomerulo- nephropathy
LM—mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson lesions, arrows in


Nonenzymatic glycosylation of GBM permeability, thickening.
Nonenzymatic glycosylation of efferent arterioles (hyaline arteriosclerosis) GFR mesangial expansion.
Most common cause of end-stage renal disease in the United States.
Kidney stones
Can lead to severe complications such as hydronephrosis, pyelonephritis. 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.
Hydronephrosis
Distention/dilation of renal pelvis and calyces A . Usually caused by urinary tract obstruction (eg, renal stones, severe BPH, 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 only one kidney.

Leads to compression and possible atrophy of renal cortex and medulla.
Renal cell carcinoma
Originates from PCT cells polygonal clear cells A filled with accumulated lipids and carbohydrates.

Often golden-yellow B due to lipid content. Most common in men 50-70 years old. incidence with smoking and obesity.

Manifests clinically with hematuria, palpable mass, 2° polycythemia, flank pain, fever, weight loss. Invades renal vein (may develop varicocele if left sided) then IVC and spreads hematogenously; metastasizes to lung and bone.

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. Associated with gene deletion on chromosome
3 (sporadic or inherited as von Hippel-Lindau
syndrome). RCC = 3 letters = chromosome 3. Associated with paraneoplastic syndromes (eg,
ectopic EPO, ACTH, PTHrP, renin).
Renal oncocytoma
Benign epithelial cell tumor arising from collecting ducts (arrows in A point to well- circumscribed mass with central scar).

Large eosinophilic cells with abundant mitochondria without perinuclear clearing
(vschromophoberenalcellcarcinoma).

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 A 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: Wilms tumor, early-onset nephrotic syndrome, male pseudohermaphroditism (WT1 mutation)

Beckwith-Wiedemann: Wilms tumor, macroglossia, organomegaly, hemihyperplasia (WT2 mutation)
Transitional cell 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.
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.
Stress incontinence
Outlet incompetence (urethral hypermobility or intrinsic sphincteric deficiency) leak with
intra-abdominal pressure (eg, sneezing, lifting). 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.

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.

Inc 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.
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.
Diffuse cortical necrosis
Acute generalized infarction of cortices of both kidneys. Likely due to a combination of vasospasm and DIC.

Associated w/ obstetric catastrophes (e.g. abruptio placentae) and septic shock
Renal osteodystrophy
Hypocalcemia, hyperphosphatemia, and failure of vitamin D hydroxylation associated with chronic renal disease 2° hyperparathyroidism.

Hyperphosphatemia also independently serum Ca2+ by causing tissue calcifications, whereas dec 1,25-(OH)2 D3 intestinal Ca2+ absorption.

Causes subperiosteal thinning of bones.
Acute kidney injury (acute renal failure)
Acute kidney injury is defined as an abrupt decline in renal function as measured by inc creatinine and inc BUN or by oliguria/anuria.
Prerenal azotemia
Due to dec RBF (eg, hypotension) dec GFR. Na+/H2O and BUN retained by kidney in an attempt to conserve volume inc BUN/creatinine ratio (BUN is reabsorbed, creatinine is not) and FENa.
Intrinsic renal failure
Generally due to acute tubular necrosis or ischemia/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 dec GFR.

Urine has epithelial/granular casts. BUN reabsorption is impaired BUN/creatinine ratio and FEN
Postrenal azotemia
Due to outflow obstruction (stones, BPH, neoplasia, congenital anomalies). Develops only with bilateral obstruction.
Consequences of Renal failure
Inability to make urine and excrete nitrogenous wastes.

Consequences (MAD HUNGER):
Metabolic Acidosis
Dyslipidemia (especially triglycerides)
Hyperkalemia
Uremia—clinical syndrome marked by
BUN:
Nausea and anorexia Pericarditis
Asterixis
Encephalopathy
Platelet dysfunction
Na+/H2O retention (HF, pulmonary edema, hypertension)

Growth retardation and developmental delay
Erythropoietin failure (anemia)
Renal osteodystrophy

2 forms of renal failure: acute (eg, ATN) and chronic (eg, hypertension, diabetes mellitus, congenital anomalies).
Acute interstitial nephritis (tubulointerstitial nephritis)
Acute interstitial renal inflammation. Pyuria (classically eosinophils) and azotemia occurring after administration of drugs that
act as haptens, inducing hypersensitivity (eg, diuretics, penicillin derivatives, proton pump inhibitors, sulfonamides, rifampin, NSAIDs).

Less commonly may be 2° to other processes such as systemic infections (eg, mycoplasma) or autoimmune diseases (eg, Sjögren syndrome, SLE, sarcoidosis).

Associated with fever, rash, hematuria, and costovertebral angle tenderness, but can be asymptomatic.
Remember these P's:
Pee (diuretics)
Pain-free (NSAIDs)
Penicillins and cephalosporins Proton pump inhibitors
RifamPin
Acute tubular necrosis
Most common cause of acute kidney injury in hospitalized patients. Spontaneously resolves in many cases.
Can be fatal, especially during initial oliguric phase. FENa.

Key finding: granular ("muddy brown") casts A . 3 stages:

1. Inciting event

2. Maintenance phase—oliguric; lasts 1-3 weeks; risk of hyperkalemia, metabolic acidosis,
uremia

3. Recovery phase—polyuric; BUN and serum creatinine fall; risk of hypokalemia

Can be caused by ischemic or nephrotoxic injury:
Ischemic—2° to renal blood flow (eg, hypotension, shock, sepsis, hemorrhage, HF). Results
in death of tubular cells that may slough into tubular lumen B (PCT and thick ascending limb
are highly susceptible to injury).

Nephrotoxic—2° to injury resulting from toxic substances (eg, aminoglycosides, radiocontrast
agents, lead, cisplatin, ethylene glycol), crush injury (myoglobinuria), hemoglobinuria. PCT is particularly susceptible to injury.
Renal papillary necrosis
Sloughing of necrotic renal papillae A gross hematuria and proteinuria.

May be triggered by recent infection or immune stimulus.

Associated with sickle cell disease or trait, acute pyelonephritis, NSAIDs, diabetes mellitus.

SAAD papa with papillary necrosis: Sickle cell disease or trait
Acute pyelonephritis
Analgesics (NSAIDs)
Diabetes mellitus
Autosomal dominant polycystic kidney disease
Numerous cysts in cortex and medulla A causing bilateral enlarged kidneys ultimately destroy kidney parenchyma.

Presents with flank pain, hematuria, hypertension, urinary infection, progressive renal failure in ~ 50% of individuals.

Mutation in PKD1 (85% of cases, chromosome 16) or PKD2 (15% of cases, chromosome 4). Death from complications of chronic kidney disease or hypertension (caused by renin production).
Associated with berry aneurysms, mitral valve prolapse, benign hepatic cysts, diverticulosis.

Treatment: ACE inhibitors or ARBs.
Autosomal recessive polycystic kidney disease
Cystic dilation of collecting ducts B . Often presents in infancy.

Associated with congenital hepatic fibrosis. Significant oliguric renal failure in utero can lead to Potter sequence.

Concerns beyond neonatal period include systemic hypertension, progressive renal insufficiency, and portal hypertension from congenital hepatic fibrosis.
Medullary cystic disease
Inherited disease causing tubulointerstitial fibrosis and progressive renal insufficiency with inability to concentrate urine.

Medullary cysts usually not visualized; shrunken kidneys on ultrasound. Poor prognosis.
Simple vs complex renal cysts
Simple cysts are filled with ultrafiltrate (anechoic on ultrasound C ).

Very common and account for majority of all renal masses.

Found incidentally and typically asymptomatic.

Complex cysts, including those that are septated, enhanced, or have solid components on imaging require follow-up or removal due to risk of renal cell carcinoma.
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