Renal Path

Question 1

Horseshoe Kidney

Answer 1

Conjoined kidney.
Connected at lower pole.
Kidney in lower abdomen bc gets caught on inferior mesenteric artery root during ascent from pelvis to abdomen.

Question 2

Renal Agenesis

Answer 2

Absent kidney formation.
Unilateral –> hypertrophy of existing kidney; hyper filtration increases risk of renal failure.
Bilateral –> oligohydramnios w lung hypoplasia, flat face, low set ears, developmental defects of extremities (aka Potter sequence); incompatible w life.

Question 3

Dysplastic Kidney

Answer 3

Noninherited.
Congenital malformation of renal parenchyma.
Cysts and abnormal tissue (i.e. cartilage).
Usu unilateral.
Bilateral - distinguish from inherited polycystic kidney disease.

Question 4

Polycystic Kidney Disease (PKD)

Answer 4

Inherited.
Bilateral enlarged kidney w cysts in renal cortex and medulla.

Autosomal recessive: infants w worsening renal failure and HTN, may have Potter sequence; assoc w congenital hepatic fibrosis (leads to portal HTN) and hepatic cysts.

Autosomal dominant: young adults w HTN (due to ^ renin), hematuria, worsening renal failure; mutation in APKD1 or APDK2 gene; cysts develop over time; assoc w berry aneurism, hepatic cysts, mitral valve prolapse.

Question 5

Medullary Cystic Kidney Disease

Answer 5

Inherited, autosomal dominant.
Cysts in medullary collecting ducts.
Parenchymal fibrosis –> shrunken kidneys and worsening renal failure.

Question 6

Acute Renal Failure (general)

Answer 6

Acute, severe decrease in renal fcn.
Develops within days.
Azotemia - increased BUN (blood urea nitrogen) and creatinine. 
Often oliguria (low urine production).
Prerenal, postrenal, and intrarenal.

Question 7

Prerenal Azotemia

Answer 7

Caused by decreased blood flow to kidneys –> v GFR, azotemia, and oliguria.
Reabsorption of fluid and BUN (serum BUN:Cr >15)
Tubular fcn intact and can still resorb Na and concentrate urine (fractional excretion sodium (FENa) < 1%; urine osmolality > 500 mOsm/kg)

Question 8

Postrenal Azotemia

Answer 8

Due to obstruction of urinary tract downstream from the kidneys.
Decreased outflow –> v GFR, azotemia, oliguria.
Early stage - ^ tubular pressure forces BUN into blood (BUN:Cr >15); tubular fcn intact (FENa<1% and urine osmolality >500).
Long-standing obstruction –> tubular damage –> decreased reabsorption of BUN (<15), decreased reabsorption of Na (FENa>2%), inability to concentrate urine (<500).

Question 9

Acute Tubular Necrosis (intrarenal azotemia)

Answer 9

Injury and necrosis of tubular epithelial cells –> ARF.
Necrotic cells plug tubules –> v GFR.
Brown granular casts.
Decreased reabsorption BUN (BUN:Cr <15)
Decreased reabsorption Na (FENa >2%)
Inability to concentrate urine (<500)
Ischemic etiology - due to decreased blood supply; often preceded by pre renal azotmeia; proximal tubule and thick ascending limb most susceptible.
Nephrotic etiology - due to toxic agents, most commonly aminoglycosides; proximal tubule; hydration and allopurinol used prior to starting chemo to decrease risk of urate-induced.
Hyperkalemia (decreased renal excretion) w metabolic acidosis.
Reversible, but may need supportive dialysis.
Oliguria can persist 2-3 weeks.

Question 10

Acute Interstitial Nephritis (intrarenal azotemia)

Answer 10

Drug-induced HSR.
Interstitium and tubules involved.
NSAIDs, penicillin, and diuretics.
Oliguria, fever, rash after starting new drug.
Eosinophils in urine.
Resolves w drug cessation.
May progress to renal papillary failure.

Question 11

Renal Papillary Necrosis

Answer 11

Necrosis of renal papillae.
Gross hematuria and flank pain.
Causes: chronic analgesic abuse, diabetes mellitus, sickle cell trait/disease, severe acute pyelonephritis.

Question 12

NephrOtic Syndrome

Answer 12

Glomerular disorder w prOteinuria (>3.5g/day) –>
-hypoalbuminemia (pitting edema)
-hypogammaglobinemia (^ risk of infection)
-hypercoaguable state (bc loss of antithrombin III)
-hyperlipidemia and hypercholesterolemia (fatty casts in urine)
Syndromes include: MCD, FSGS, membranous nephropathy, membranoproliferative glomerulonephritis, diabetes mellitus, systemic amyloidosis.

Question 13

Minimal Change Disease (MCD)

Answer 13

Most common nephrotic syndrome in kids.
Idiopathic.
Assoc w Hodgkin lymphoma.
Normal glomeruli on H&E.
Effacement of foot processes on EM.
Negative immunofluorescence - no immune complex deposits.
Selective proteinuria - loss of albumin, not immunoglobulin.
Treat w steroids.

Question 14

Focal Segmental Glomerulonephritis (FSGN)

Answer 14

Most common nephrotic syndrome in Hispanics and African Americans.
Idiopathic.
Assoc w HIV, heroin use, sickle cell disease.
Focal (some glomeruli) segmental (only part of glomerulus) sclerosis on H&E.
Effacement of foot processes on EM.
Negative IF.
Poor response to steroids.
–> chronic renal failure.

Question 15

Membranous Nephropathy

Answer 15

Most common nephrotic syndrome in Caucasian adults.
Idiopathic.
Assoc w hep B or C, solid tumors, SLE, or drugs.
Thick glomerular basement membrane on H&E.
Due to immune complex deposition - granular IF.
Subepithelial deposits w “spike and dome” on EM.
Poor response to steroids.
–> chronic renal failure.

Question 16

Membranoproliferative Glomerulonephritis

Answer 16

Thick glomerular basement membrane on H&E.
Due to immune complex deposition - granular IF.
Type I: subendothelial deposits; assoc w HBV and HCV; “tram track” appearance.
Type II: dense deposit disease - intramembranous deposits; assoc w C3 nephritic factor (autoAb that stabilizes C3 convertase –> over activation of complement, inflammation, low levels of circulating C3).
Poor response to steroids.
–> chronic renal failure.

Question 17

Diabetes Mellitus

Answer 17

High serum glucose –> nonenzymatic glycosylation of vascular basement membrane - makes membrane leaky and protein enters –> hyaline arteriosclerosis.
Glomerular efferent arteriole more affected –> high glomerular filtration pressure.
Hyperfiltration injury –> microalbuminuria.
Progresses –> nephrotic syndrome.
Sclerosis of mesangium and Kimmelstiel Wilson nodules.
ACE inhibitors slow progression.

Question 18

Systemic Amyloidosis

Answer 18

Kidney most commonly involved.
Amyloid deposits in the mesangium –> nephrotic syndrome.
Apple-green birefringence under polarized light after Congo red stain.

Question 19

Nephr-I-tic Syndrome

Answer 19

Glomerular disorder w I-nflammation and bleeding.
Limited proteinuria (<3.5 g/day).
Oliguria and azotemia.
Salt retention w periorbital edema and HTN.
RBC casts and dysmorphic RBCs.
Hypercellular, inflamed glomeruli.
Immune complex deposition activates complement - C5a attracts neutrophils –> damage.
Includes PGSN, rapidly progressive glomerulonephritis, IgA nephropathy, alport syndrome.

Question 20

Poststreptococcal Glomerulonephritis (PSGN)

Answer 20

Nephritic syndrome that arises after group A beta-hemolytic strep infection of the skin or pharynx.
Nephritogenic strains carry M protein virulence factor.
2-3 weeks after the infection - hematuria (cola colored urine), oliguria, HTN, periorbital edema.
Usu in kids.
Hypercellular, inflamed glomeruli on H&E.
Immune complex deposition - granular IF.
Subepithelial “humps” on EM.
Supportive treatment.
Some adults –> RPGN.

Question 21

Rapidly Progressive Glomerulonephritis (RPGN)

Answer 21

Nephritic syndrome –> renal failure in weeks-months.
Crescents in Bowman’s space on H&E - crescents composed of fibrin and macrophages.

Linear IF (ant-basement membrane Ab) - Goodpasture syndrome - Ab against collagen in glomerular and alveolar basement membrane - hematuria and hemoptysis - young, adult males.

Granular IF (immune complex deposition) - PSGN or diffuse proliferative glomerulonephritis - diffuse antigen antibody complex deposition, usu sub-endothelial - assoc w SLE.

Negative IF (pauci-immune) - Wegener granulomatosis (c-ANCA), microscopic polyangiitis (p-ANCA), or Churg-Strauss syndrome (granulomatous inflammation, eosinophilia, asthma)

Question 22

IgA Nephropathy (Berger Disease)

Answer 22

Most common nephrotic syndrome.
IgA immune complex deposition in mesangium - seen on IF.
Children present w episodic gross or microscopic hematuria w RBC casts - usu after a mucosal infection (^IgA).
May slowly –> renal failure.

Question 23

Alport Syndrome

Answer 23

Nephrotic syndrome.
Inherited defect in type IV collagen - usu X-linked.
–> thinning and splitting of glomerular basement membrane.
Isolated hematuria, sensory hearing loss, ocular disturbances.

Question 24

UTIs (general)

Answer 24

Infection of urethra, bladder, or kidneys.
Usu. ascending infection.
Females.
Risk factors: sexual intercourse, urinary stasis, catheters.

Question 25

Cystitis

Answer 25

Infection of bladder.
Usu no systemic signs.
Dysuria, urinary frequency, urgency, suprapubic pain.
Cloudy urine w >10 WBCs/hpf.
Positive leukocyte esterase and nitrites.
>100,000 colony forming units.
E. coli (80%), Staph. saprophytic (young, sexually active females), Klebsiella pneumoniae, Proteus mirabilis (alkaline urine w ammonia scent), Enterococcus faecalis.
Sterile pyuria (pyuria w negative urine culture) –> urethritis due to Chlamydia or gonorrhoeae.

Question 26

Pyelonephritis

Answer 26

Infection of kidney.
Ascending infection usu.
^ risk w vesicourecteral reflux.
Fever, flank pain, WBC casts, leukocytosis, and cystitis symptoms.
E. coli (90%), Enterococcus faecalis, Klebsiella species.

Question 27

Chronic Pyelonephritis

Answer 27

Multiple bouts acute pyelonephritis –> interstitial fibrosis and atrophy of tubules.
Due to vesicoureteral reflux (kids) or obstruction.
–> cortical scarring w blunted calyces; scarring upper and lower poles.
Atrophic tubules w eosinophilia proteinaceous material (“thyroidization” of kidney).
Waxy casts.

Question 28

Nephrolithiasis (general)

Answer 28

Precipitation of urinary solute as kidney stone.
Risk factors: high concentration of solute in filtrate and low urine volume.
Colicky pain w hematuria and unilateral flank tenderness.
Stone passed within hrs or els may need surgery.

Question 29

Calcium oxalate/calcium phosphate stone

Answer 29

Most common type. Usu adults.
Cause: idiopathic hypercalciuria; must exclude hypercalcemia; also Crohn disease.
Treat: hydrochlorothiazide (calcium-sparing diuretic).

Question 30

Ammonium magnesium phosphate stone

Answer 30

Second most common type of kidney stone.
Cause: infection w urease-positive organism (proteus vulgaris or Klebsiella); alkaline urine –> stone.
Results in stag horn calculi in renal calyces - nidus for UTIs.
Treat: surgical removal and eradication of pathogen.

Question 31

Uric acid stone

Answer 31

3rd most common kidney stone (5%).
Radiolucent!
Risk factors: hot, arid climates, low urine volume, acidic pH, hyperuricemia (leukemia and myeloproliferative disorders)
Assoc w gout.
Treat: hydration and alkalinization of urine (potassium bicarb), allopurinol for gout patients.

Question 32

Cystine stone

Answer 32

Rare cause of kidney stones - usu kids.
Assoc w cystinuria (genetic defect of tubules –> v reabsorption of cysteine).
May form stag horn calculi.
Treat: hydration an alkalinization of urine.

Question 33

Chronic Renal Failure

Answer 33

End-stage kidney failure.
Common causes: diabetes, HTN, glomerular disease.
Uremia (increased nitrogenous waste products in blood - azotemia).
Salt and water retention–> HTN.
Hyperkalemia and metabolic acidosis.
Anemia due to decreased erythropoietin production by renal peritubular interstitial cells.
Hypocalcemia due to decreased 1-alpha-hydroxylation of vitamin D by proximal tubule cells and hyperphosphatemia (bc phosphate binds calcium).
Renal osteodystrophy due to secondary hyperparathyroidism, osteomalacia, and osteoporosis.
Treat: dialysis, renal transplant.
Dialysis may –> cysts in shrunken end-stage kidneys –> increased risk of carcinoma.

Question 34

Angiomyolipoma

Answer 34

Harmatoma of blood vessels, smooth muscle, and adipose tissue.
Assoc. w tuberous sclerosis.

Question 35

Renal Cell Carcinoma

Answer 35

Malignant epithelial tumor arising from kidney tubules.
Triad: hematuria, palpable mass, flank pain (rarely all 3)
May have fever, weight loss, or paraneoplastic syndrome.
Rarely may have left-sided varicocele: involvement of left renal vein blocks drainage of left spermatic vein (not an issue on the right bc right spermatic vein drains directly into IVC).
Yellow mass.
Commonly clear cytoplasm.
Loss of VHL (3p) tumor suppressor gene –> ^ IGF-1 (promotes growth) and ^ HIF transcription factor (^VEGF and PDGF).
Sporadic tumors: adult male (60 yo), single tumor in upper pole, risk factor is smoking.
Hereditary tumors: younger adults, bilateral, Von Hippel-Lindau disease (autosomal dominant, inactivation of VHL gene –> risk of hemangioblastoma of cerebellum and renal cell carcinoma).
Staging: T (size and involvement of renal veins –> hematogenous spread to lungs and bones), N (spread to retroperitoneal lymph nodes.

Question 36

Wilms Tumor

Answer 36

Malignant kidney tumor of blastema (immature kidney mesenchyme), primitive glomeruli and tubules, and stromal cells.
Common in kids (3 yo).
Large, unilateral flank mass w hematuria and HTN (renin secretion).
90% sporadic.
WAGR syndrome - Wilms tumor, Aniridia, Genital abnormalities, mental and motor Retardation; deletion of WT1 tumor suppressor gene (at 11p13).
Denys-Drash syndrome - Wilms tumor, progressive renal (glomerular) disease, male pseudohermaphroditism; mutations of WT1.
Beckwith-Wiedemann syndrome - Wilms tumor, neonatal hypoglycemia, muscular hemihypertrophy, organomegaly (including tongue); mutation in WT2 gene cluster, particularly IGF-2.

Question 37

Urothelial (Transitional Cell) Carcinoma

Answer 37

Malignant tumor from urothelial lining of renal pelvis, ureter, bladder, or urethra.
Most common lower urinary tract cancer.
Usu bladder.
Risk factors: smoking, naphthylamine, azo dyes, long-term cyclophosphamide or phenacetin use.
Older adults.
Painless hematuria.
Flat: develops as high-grade flat tumor then invades; early p53 mutation.
Papillary: develops as low-grade papillary tumor then progresses to high-grade papillary tumor then invades.
Often multifocal and recur (“field defect” - entire urothelieum hit w carcinogens and is mutated).

Question 38

Squamous Cell Carcinoma

Answer 38

Malignant squamous cell proliferation.
Usu involves bladder.
Arises in background of squamous metaplasia.
Risk factors: chronic cystitis (old women), Schistosoma haematobium infection (Middle Eastern male), long-standing nephrolithiasis.

Question 39

Adenocarcinoma

Answer 39

Malignant proliferation of glands.
Usu involves bladder.
Arises from urachal remnant (duct connecting fetal bladder w yolk sac, allowing the bladder to drain; tumor in dome of bladder), cystitis glandularis (chronic inflammation of bladder–> columnar metaplasia –> adenocarcinoma), or exstrophy (congenital failure to form the caudal portion of the anterior abdominal and bladder walls, thus exposing surface of bladder to outside world)