Renal

Question 1

Horseshoe Kidney

Answer 1

Conjoined kidneys usually connected at the lower pole ; most common congenital renal anomaly

Kidney is abnormally located in the lower abdomen; horseshoe kidney gets caught on the inferior mesenteric artery root during its ascent from ihe pelvis to the abdomen.

Question 2

Renal Agenesis

Answer 2

Absent kidney formation; may be unilateral or bilateral

Unilateral agenesis leads to hypertrophy of the existing kidney; hyperfiltration increases risk of rena) failure later in life.

Bilateral agenesis leads to oligohydramnios with lung hypoplasia, flat face with low set ears, and developmental detects of the extremities (Potter sequence).; incompatible with life

Question 3

Dysplastic Kidney

Answer 3

Noninhericed, congenital malformation of the renal parenchyma characterized by cysts and abnurmal tissue (e.g., cartilage)

Usually unilateral; when bilateral, must be distinguished from inherited polycystic kidney disease

Question 4

Polycystic Kidney Disease

Answer 4

Inherited defect leading to bilateral enlarged kidneys with cysts in the renal cortex and medulla

• *Autosomal recessive** form presents in infants as worsening renal failure and hypertension; newborns may present with Potter sequence.
  1. Associated with congenital hepatic fibrosis (leads to portal hypertension) and hepatic cysts
• *Autosomal dominant** form presents in young adults as hypertension (due to increased renin), hematuria, and worsening renal failure,
  1. Due to mutation in the APKD1 or APKD2gene; cysts develop over time.

2. Associated with berry aneurysm, hepatic cysts, and mitral valve prolapse

Question 5

Medullary Cystic Kidney Disease

Answer 5

Inherited (autosomal dominant) defect leading to cysts in the medullary collecting ducts
Parenchymal fibrosis results in shrunken kidneys and worsening renal failure.

Question 6

Acute Renal Failure

Answer 6

Acute, severe decrease in renal function (develops within days)
Hallmark is azotemia (increased BUN and creatinine [Cr|), often with oliguria.

Question 7

Prerenal Azotemia

Answer 7

Aute Renal Failure

• Due to decreased blood flow to kidneys (e.g., cardiac failure); common cause of ARE
• Decreased blood How results in I GFR, azotemia, and oliguria.
• Reabsorption of fluid and BUN ensues (serum BUN:Cr ratio > 15); tubular function remains intact (fractional excretion of sodium [FENa] < 1% and urine osmolality [osm] > 500 mOsm/kg).

Question 8

Post Renal Azotemia

Answer 8

Acute Renal Failure

• Due to obstruction of urinary tract downstream from the kidney (e.g., ureters)
• Decreased outflow results in in GFR, azotemia, and oliguria.
• During early stage of obstruction, increased tubular pressure “forces” BUN into the blood (serum BUN;Cr ratio > 15); tubular function remains intact (FENa < 1% and urine osm > 500 mOsm/kg).
• With long-standing obstruction, tubular damage ensues, resulting in decreased reabsorption of BUN (serum BUN:Cr ratio < 15), decreased reabsorption of sodium (FeNa > 2%), and inability to concentrate urine (urine osm < 500 mOsm/kg).

Question 9

Acute Tubular Necrosis

Answer 9

• Injury and necrosis of tubular epithelial cells ; most common cause of acute renal failure (intrarenal azotemia)
• Necrotic cells plug tubules; obstruction decreases GFR.
• Brown, granular casts are seen in the urine.
• Dysfunctional tubular epithelium results in decreased reabsorption of BUN (serum BUN:Cr ratio < 15), decreased reabsorption of sodium (FENa > 2%), and inability to concentrate urine (urine osm < 500 mOsm/kg).
• Etiology may be ischemic or nephrotoxic,
  
  • Ischemia—Decreased blood supply results in necrosis of tubules. Often preceded by prerenal azotemia
  • Proximal tubule and medullary segment of the thick ascending limb are particularly susceptible to ischemic damage.
  • Nephrotoxic—Toxic agents result in necrosis of tubules.
  • Causes include aminoglycosides (most common), heavy metals (e.g., lead), myoglobinuria (e.g., from crush injury to muscle), ethylene glycol (associated with oxalate crystals in urine), radiocontrast dye, and urate (e.g., tumor lysis syndrome).
• Hydration and allopurinol are used prior to initiation of chemotherapy to decrease risk of urate-induced ATN.
• Clinical feature
  • Oliguria with brown, granular casts
  • Elevated BUN and creatinine
  • Hyperkalemia (due to decreased renal excretion) with metabolic acidosis
• Reversible, but often requires supportive dialysis since electrolyte imbalances can be fatal. Oliguria can persist for 2-3 weeks before recovery; tubular cells (stable cells) take time to reenter the cell cycle and regenerate.

Question 10

Acute Interstitial Nephritis

Answer 10

• Drug-induced hypersensitivity involving the interstitium and tubules results in acute renal failure (intrarenal azotemia)
• Causes include NSAIDs, penicillin, and diuretics.
• Presents as oliguria, fever, and rash days to weeks after starting a drug; eosinophils may be seen in urine.
• Resolves with cessation of drug
• May progress to renal papillary necrosis

Question 11

Renal Papillary Necrosis

Answer 11

• Necrosis of renal papillae
• Presents with gross hematuria and flank pain
• Causes include
  
  • Chronic analgesic abuse (e.g., long-term phenacetin or aspirin use)
  • Diabetes mellitus
  • Sickle cell trait or disease
  • Severe acute pyelonephritis

Question 12

Nephrotic Syndrome

Answer 12

Glomerular disorders characterized by proteinuria (> 3.5 g/day) resulting in

• Hypoalbuminemia—pitting edema
• Hypogammaglobulinemia—increased risk of infection
• Hypercoagulable state—due to loss of antithrombin III
• Hyperlipidemia and hypercholesterolemia—may result in fatty casts in urine

Question 13

Minimal Change Disease

Answer 13

• Most common cause of nephrotic syndrome in children
• Usually idiopathic; may be associated with Flodgkin lymphoma
• Normal glomeruli on H&E stain; lipid maybe seen in proximal tubule cells
• Effacement of foot processes on electron microscopy
• No immune complex deposits; negative immunofluorescence (IF)
• Selective proteinuria (loss of albumin, but not immunoglobulin)
• Excellent response to steroids (damage is mediated by cytokines from T cells)

Question 14

Focal Segmental Glomerulosclerosis

Answer 14

• Most common cause of nephrotic syndrome in Hispanics and African Americans Usually idiopathic; maybe associated with HIV, heroin use, and sickle cell disease
• Focal (some glomeruli) and segmental (involving only part of the glomerulus) sclerosis on H&E stain
• Effacement of foot processes on EM
• No immune complex deposits; negative IF
• Poor response to steroids; progresses to chronic renal failure

Question 15

Membranous Nephropathy

Answer 15

• Most common cause of nephrotic syndrome in Caucasian adults
• Usually idiopathic; may be associated with hepatitis B or C, solid tumors, SLE, or drugs (e.g., NSAIDs and penicillamine)
• Thick glomerular basement membrane on H&E
• Due to immune complex deposition (granular IE); subepithelial deposits with ‘spike and dome’ appearance on EM
• Poor response to steroids; progresses to chronic renal failure

Question 16

Membranoproliferative Glomerulonephritis

Answer 16

• Thick glomerular basement membrane on H&E, often with ‘tram-track’ appearance
• Due to immune complex deposition (granular IF)
• Divided into two types based on location of deposits
  
  • Type I—subendothelial; associated with HBV and HCV
  • Type II (dense deposit disease)—intra membra no us; associated with C3 nephritic factor (autoantibody that stabilizes C3 convertase, leading to overactivation of complement, inflammation, and low levels of circulating C3)
• Poor response to steroids; progresses to chronic renal failure

Question 17

Diabetes Mellitus

Answer 17

• High serum glucose leads to nonenzymatic glycosylation of the vascular basement membrane resulting in hyaline arteriolosclerosis.
• Glomerular efferent arteriole is more affected than the afferent arteriole, leading to high glomerular filtration pressure. Hyperfiltration Injury leads to microalbuminuria,
• Eventually progresses to nephrotic syndrome. Characterized by sclerosis of the mesangium with formation of Kimmelstiel-Wilson nodules
• ACE inhibitors slow progression of hyperfiltration induced damage.

Question 18

Systemic Amylodosis

Answer 18

• Kidney is the most commonly involved organ in systemic amyloidosis.
• Amyloid deposits in the mesangium, resulting in nephrotic syndrome
• Characterized by apple-green birefringence under polarized light after staining with Congo Red

Question 19

Nephritic Syndrome

Answer 19

• Glomerular disorders characterized by glomerular inflammation and bleeding
  
  • Limited proteinuria (< 3.5 g/day)
  • Oliguria and azotemia
  • Salt retention with periorbital edema and hypertension
  • RBC casts and dysmorphic RBCs in urine
• Biopsy reveals hypercellular, inflamed glomeruli
• Immune-complex deposition activates complement; C5a attracts neutrophils,which mediate damage

Question 21

Post Streptococcal Glomerulonephritis

Answer 21

• Nephritic syndrome that arises alter group A |3-he mo lytic streptococcal infection Of the skin (impetigo) or pharynx
  
  • Occurs with nephritogenic strains (which carry the M protein virulence factor)
  • May occur after infection with nonstreptococcal organisms as well
• Presents 2-3 weeks after infection as hematuria (cola-colored urine), oliguria, hypertension, and periorbital edema
• Usually seen in children, but may occur in adults
• Hypercellular, inflamed glomeruli on H&E
• Mediated by immune complex deposition (granular IF); subepithelial ‘humps’ on EM

Treatment is supportive.

1. Children rarely (1%) progress to renal failure.
2. Some adults (25%) develop rapidly progressive glomerulonephritis (RPGN).

Question 22

Rapidly Progressive Glomerulonephritis

Answer 22

• Nephritic syndrome that progresses to renal failure in weeks to months
• Characterized by crescents in Bowman space (of glomeruli) on H&E stain; crescents are comprised of fibrin and macrophages
• Clinical picture and IF help resolve etiology

Question 23

IgA Nephropathy

Berger Disease

Answer 23

• IgA immune complex deposition in mesangium of glomeruli; most common nephropathy worldwide
• Presents during childhood as episodic gross or microscopic hemaluria with RBC casts, usually following mucosal infections (e.g., gastroenteritis) IgA production is increased during infection.
• IgA immune complex deposition in the mesangium is seen on IF (Fig. 12.16).
• May slowly progress to renal failure

Question 24

Alport Syndrome

Answer 24

• Inherited defect in type IV collagen; most commonly X-linked
• Results in thinning and splitting of the glomerular basement membrane
• Presents as isolated hematuria, sensory hearing loss, and ocular disturbances

Question 25

Cystitis

Answer 25

• Infection of the bladder
• Presents as dysuria, urinary frequency, urgency, and suprapubic pain; systemic signs (e.g., fever) are usually absent.
• Laboratory findings
  
  • Urinalysis—cloudy urine with > 10 WBCs/high power field (hpf)
  • Dipstick—Positive leukocyte esterase (due to pyuria) and nitrites (bacteria convert nitrates to nitrites)
  • Culture—greater than 100,000 colony forming units (gold standard)

Etiology

• E.colU80%)
• Staphylococcus saprophytics—increased incidence in young, sexually active women (but E coll is still mure common in this population)
• Klebsiella pneumoniae
• Proteus mirabilis—alkaline urine with ammonia scent
• Enterococcus faecalis
• Sterile pyuria is the presence of pyuria (> 10 WBCs/hpf and leukocyte esterase) with a negative urine culture.
  
  • Suggests urethritis due to Chlamydia trachomatis or Neisseria gonorrhoeae (dominant presenting sign of urethritis is dysuria)

Question 26

Pyelonephritis

Answer 26

• Infection of the kidney
• Usually due to ascending infection; increased risk with vesicoureteral reflux
• Presents with fever, flank pain, WBC casts, and leukocytosis in addition to symptoms of cystitis
• Most common pathogens are
  
  • E coli (90%)
  • Klebsiella species
  • Enterococcus faecalis

Question 27

Chronic Pyelonephritis

Answer 27

• Interstitial fibrosis and atrophy of tubules due to multiple bouts of acute pyelonephritis
• Due to vesicoureteral reflux (children) or obstruction (e.g., BPH or cervical carcinoma)
• Leads to cortical scarring with blunted calyces; scarring at upper and lower poles is characteristic of vesicoureteral reflux.

Atrophic tubules containing eosinophilic proteinaceous material resemble thyroid

follicles (‘thyroidNation’ of the kidney, Fig. 12.17); waxy casts may be seen in urine.

Question 28

Chronic Renal Failure

Answer 28

End-stage kidney failure

• May result from glomerular, tubular, inflammatory, or vascular insults
• Most common causes are diabetes mellitus, hypertension, and glomerular disease,

Clinical Features

• Uremia—Increased nitrogenous waste products in blood (azotemia) result in nausea, anorexia, pericarditis, platelet dysfunction, encephalopathy with asterixis, and deposition of urea crystals in skin,
• Salt and water retention with resultant hypertension
• Hyperkalemia with metabolic acidosis
• Anemia due to decreased erythropoietin production by renal peritubular interstitial cells
• Hypocalcemia due to decreased l-alpha-hydroxylation ofvitamin D by proximal renal tubule cells and hyperphosphatemia
• Renal osteodystrophy due to secondary hyperparathyroidism, osteomalacia, and osteoporosis

Question 29

Nephrolithiasis:

Calcium oxalate and/or Calcium phosphate

Answer 29

• Most common cause is idiopathic livpercalciuria; hypercalcemia and its related causes must be excluded.
• Also seen with Crohn disease
• Treatment is hydrochlorothiazide (caicium-sparingdiuretic).

Question 30

Nephrolithiasis:

Ammonium Magnesium Phosphate

Answer 30

• Most common cause is infection with urease-positive organisms( vulgaris or Klebsiella), alkaline urine leads to formation of stone.
• Classically, results in staghorn calculi in renal calyces, which act as a nidus tor urinary tract infections. Treatment involves surgical removal of stone (due to size) and eradication of pathogen (to prevent recurrence).

Question 31

Nephrolithasis:

Uric Acid

Answer 31

• Risk factors include hot, arid climates, low urine volume, and acidic pH. Most common stone seen in patients with gout; hyperuricemia (e.g., in leukemia or myeloproliferative disorders) increases risk.
• Treatment involves hydration and alkalimzation of urine (potassium bicarbonate); allopurinol is also administered in patients with gout.

Question 32

Nehprolithiasis:

Cysteine

Answer 32

• Rare cause of nephrolithiasis; most commonly seen in children
• Associated with cystinuria (a genetic defect of tubules that results in decreased reabsorption of cysteine)
• May form staghorn calculi; treatment involves hydration and alkalinization of urine.

Question 33

Angiomyolipoma

Answer 33

• Hamartoma comprised of blood vessels, smooth muscle, and adipose tissue
• Increased frequency in tuberous sclerosis

Question 34

Renal Cell Carcinoma

Answer 34

• Malignant epithelial tumor arising from kidney tubules
• Presents with classic triad of hematuria, palpable mass, and flank pain
  • All three symptoms rarely occur together; hematuria is the most common symptom.
  • Fever, weight loss, or paraneoplastic syndrome (e.g., EPO, renin, PTHrP , or ACT H) may also be present.
  • Rarely may present with left-sided varicocele
    i. Involvement of the left renal vein by carcinoma blocks drainage of the left spermatic vein leading to varicocele.
    ii. Right spermatic vein drains directly into the IVC; hence, right-sided varicocele is not seen.
• Gross exam reveals a yellow mass (Fig. 12.19A); microscopically, the most common variant exhibits clear cytoplasm (clear cell type.
• Pathogenesis involves loss of VHl (3p) tumor suppressor gene, which leads to increased IGF-l (promotes growth) and increased HIF transcription factor (increases VF.GF and PDGF).

Tumors may be hereditary or sporadic.

• Sporadic tumors classically arise in adult males (average age is 60 years) as a single tumor in the upper pole of the kidney; major risk factor for sporadic tumors is cigarette smoke.
• Hereditary tumors arise in younger adults and are often bilateral,
• Von Hippel-Lindau disease is an autosomal dominant disorder associated with inactivation of the VHL gene leading to increased risk tor hemangioblastoma of the cerebellum and renal cell carcinoma.

Staging

• T—based on size and involvement of the renal vein (occurs commonly and increases risk of hematogenous spread to the lungs and bone)
• N—spread to retroperitoneal lymph nodes

Question 35

Wilms Tumor

Answer 35

• Malignant kidney tumor comprised of blastema (immature kidney mesenchyme), primitive glomeruli and tubules, and stromal cells
• Most common malignant renal tumor in children; average age is 3 years
• Presents as a large, unilateral flank mass with hematuria and hypertension (due to renin secretion

Associated with WT1 mutation, especially in syndromic cases

1. WAGR syndrome—Wilms tumor, Aniridia, Genital abnormalities, and mental and motor Retardation
2. Beckwith-Wiedemann syndrome—Wilms tumor, neonatal hypoglycemia, muscular hemihypertrophy, and organomegaly (including tongue)

Question 36

Urothelial Carcinoma

Answer 36

• A. Malignant tumor arising from the urothelial lining of the renal pelvis, ureter, bladder, or urethra
• Most common type of lower urinary tract cancer; usually arises in the bladder
• Major risk factor is cigarette smoke; additional risk factors are naphthylamine, axo dyes, and long-term cyclophosphamide or phenacetin use.
• Generally seen in older adults; classically presents with painless hematuria
• Arises via two distinct pathways
  
  • Flat—develops as a high-grade flat tumor and then invades; associated with early p53 mutations
  • Papillary—develops as a low-grade papillary tumor that progresses to a high- grade papillary tumor and then invades; not associated with early p53 mutations
• Tumors are often multifocal and recur (“field detect”).

Question 37

Squamous Cell Carcinoma

Answer 37

• Malignant proliferation of squamous cells, usually involving the bladder
• Arises in a background of squamous metaplasia (normal bladder surface is not lined by squamous epithelium)
• Risk factors include chronic cystitis (older woman). Schistosoma hematobium infection (Egyptian male), and long-standing nephrolithiasis.

Question 40

Adenocarcinoma

Answer 40

• A. Malignant proliferation of glands, usually involving bladder
• Arises from a urachal remnant (tumor develops at the dome ol the bladder), cystitis glandularis, or exstrophy (congenital failure to form the caudal portion of the anterior abdominal and bladder walls)