Kidney and Urinary Tract

Question 1

Horseshoe Kidney

Answer 1

Conjoined kidneys usually connected at lower pole
MOST COMMON congenital renal anomaly
Kidneys are abnormally located in the lower abdomen as they get stuck on the Inferior Mesenteric Artery during its ascent from the pelvis

Question 2

Renal Agenesis

Answer 2

Absent kidney formation
Unilateral = hypertrophy of existing kidney. Hyperfiltration increases the risk of renal failure later in life
Bilateral = get oligohydraminos with potter sequence (lung hypoplasia, flat face with low set ears, developmental defects of the extremities)
Incompatible with life

Question 3

Potter Sequence

Answer 3

lung hypoplasia
flat face with low set ears
developmental defects of the extremities
See in congenital kidney diseases like bilateral renal agenesis and PKD

Question 4

Dysplastic Kidney

Answer 4

NONINHERITED, congenital malformation of renal parenchyma characterized by cysts and abnormal tissue (cartilage)
usually unilateral but can be bilateral (especially on tests)

Question 5

Polycystic Kidney Disease Autosomal Recessive

Answer 5

Inherited defect leading to bilateral enlarged kidneys with cysts in the RENAL CORTEX and MEDULLA
Autosomal Recessive = Presents in INFANTS as worsening renal failure and hypertension and possibly potter sequence. Associated with congenital hepatic fibrosis (get portal hypertension) and hepatic cysts

Question 6

Polycystic Kidney Disease Autosomal Dominant

Answer 6

Inherited defect leading to bilateral enlarged kidneys with cysts in the RENAL CORTEX and MEDULLA
Autosomal Dominant = See in young ADULTS as hypertension (from increased renin), hematuria, and worsening renal failure.
Due to mutations in APK1 or APKD2.
Associated with berry aneurysm, hepatic cysts, and mitral valve prolapse

Question 7

Medullary Cystic Kidney Disease

Answer 7

Inherited (aut DOM) defect leading to cysts in the MEDULLARY COLLECTING DUCTS
Parenchymal fibrosis results in SHRUNKEN kidneys and worsening renal failure

Question 8

Acute Renal Failure

Answer 8

Hallmark is azotemia , increased BUN and Creatinine, and oliguria
Can be prerena;, postrenal, or intrarenal

Question 9

Prerenal Azotemia

Answer 9

Due to decreased blood flow to kidneys → decreased GFR, azotemia and oliguria
activation of renin/angiotensin system ultimately leads to increased reabsorption of BUN (serum BUN:Cr ratio >15)
Tubular function remains intact so fractional excretion of 500mOsm/kg

Question 10

Postrenal Azotemia

Answer 10

Obsturction of urinary tract causes a backpressure in the kidney that decreases GFR, azotemia, and oliguria
Early Stage = increased tubular back pressure forces BUN into the serum (serum BUN:Cr ratio >15) and Tubular function remains intact so fractional excretion of 500mOsm/kg
Long standing obstruction = get tubular damage and get decreased reabsorption of BUN (serum BUN:Cr 2% and inability to concentrate the urine (urine osm<500mOsm/kg)

Question 11

Acute Tubular Necrosis

Answer 11

Injury and necrosis of tubular epithelial cells.
Necrotic cells slough off and plug the tubules and decrease GFR.
Oliguria, brown granular casts in urine, elevated BUN and creatinine, hyperkalemia, metabolic acidosis with increased anion gap
Reversible but generally need to be on dialysis for 2-3 weeks until the tubular/stable cells reenter the cell cycle and regenerate
Dysfunctional epithelium results in decreased reabsorption of BUN (serum BUN:Cr 2% and inability to concentrate the urine (urine osm<500mOsm/kg)
Etiology may be ischemic or nephrotoxic

Question 12

Acute Tubular Necrosis from Ischemia

Answer 12

decreased blood supply results in necrosis of tubules
Often preceded by prerenal azotemia
PROXIMAL TUBULE and MEDULLARY SEGMENT of THICK ASCENDING LIMB are particularly susceptible to ischemic damage since these segments require a lot of ATP

Question 13

Acute Tubular Necrosis from nephrotoxic

Answer 13

Toxic agents kill tubules
Proximal tubule is particularly susceptible
Causes include:
1) AMINOGLYCOSIDES
2) heavy metals = lead
3) Myoglobinuria = crush injury to muscle
4) Ethylene glycol = see OXALATE CRYSTALS in urine
5) Radiocontrast dye
6) Urate = tumor lysis syndrome (Prevent with hydration and allopurinol prior to chemo)

Question 14

Acute Interstitial Nephritis

Answer 14

Drug induced hypersensitivity involving the interstitium and tubules results in acute renal failure
Causes include NSAIDS, PENICILLIN, and DIURETICS
Presents as oliguria, fever, and rash days to weeks after starting a med
EOSINOPHILS in urine
resolves with removal of drug but can progress to renal papillary necrosis

Question 15

Renal Papillary Necrosis

Answer 15

Necrosis of renal papillae
Presents with gross hematuria and flank pain
Causes include:
1)Chronic analgesic abuse (long term phenacetin or aspirin use)
2) Diabetes mellitus
3) Sickle cell trait or disease
4) Severe acute pyelonephritis

Question 16

Nephrotic Syndrome

Answer 16

Glomerular disorder characterized by proteinuria (>3.5g/day) resulting in:
Hypoalbuminemia = pitting edema
hypogammaglobulinemia = increased risk of infection
Hypercoaguable state = due to loss of antithrombin III
hyperlipidemia and hypercholesterolemia

Question 17

Minimal Change Disease

Answer 17

CHILDREN
idiopathic usually but also associated with Hodgkin Lymphoma (overproduction of cytokines)
EFFACEMENT of PODOCYTES via CYTOKINES on electron microscopy
Seletive proteinuria = loss of albumin but not immunoglobulin
Excellent response to steroids
Normal glomeruli on H&E stain, no immune complex deposits so negative IF

Question 18

Focal Segmental Glomerulosclerosis

Answer 18

HISPANICS and AFRICAN AMERICANS
usually idiopathic but also associated with HIV, HEROIN, and SICKLE CELL DISEASE
Focal in that only some glomeruli are affected and segmental in that of those glomeruli that are affected only parts of them show sclerosis on H&E
Effacement of foot processes on EM
No immune complexes depsotis so negative IF
Poor response to steroids and progresses to chronic renal failure

Question 19

Membranous Nephropathy

Answer 19

CAUSCASIAN ADULTS
usually idiopathic but also associated with Hep B+C, solid tumors, SLE, or drugs like NSAIDs and penicillamine
Get a THICK glomerular BASEMENT MEMBRANE on H&E due to subepithelial immune complex deposition.
GRANNULAR IF, subepithelial “spike and dome” appearance on EM
Poor response to steroids and progresses to chronic renal failure

Question 20

Membranoproliferative Glomerulonephritis

Answer 20

THICK glomerular BASEMENT MEMBRANE on H&E with “TRAM TRACK” appearance due to immune complex deposition
GRANULAR IF
Type I = subenothelial complex deposition. associated with Hep B and C. “tram track” appearance seen more clearly
Type II = dense intremembranous complex disease. Associated with C3 nephritic factor (an autoantibody that stabilizes C3 convertase, leading to overactivation of complement, inflammation, and low levels of circulating C3)
Poor response to steroids and progresses to chronic renal failure

Question 21

Diabetes Mellitus Nephrotic Syndrome

Answer 21

High serum glucose leads to nonenzymatic glycosylation of the vascular basement membrane resulting in HYALINE ARTERIOSCLEROSIS
glomerular EFFERENT ARTERIOLE is affected more than afferent leading to high glomerular filtration pressure. Leads to hyperfiltration injury leads to microalbunemia.
Eventually progresses to nephrotic syndrome that is characterized by sclerosis of the mesangium with formation of Kimmesltiel-Wilson nodules

Question 22

Systemic Amyloidosis

Answer 22

Kidney is most commonly involved organ. Amyloid deposits in the mesangium resulting in nephrotic syndrome
get apple-green birefringence

Question 23

Nephritic Syndrome

Answer 23

Glomerular disorders characterized by inflammation and bleeding.
See limited: proteinuira, oliguria, azotemia, salt rentention (periorbital edema and hypertension) RBC casts
HYPERCELLULAR and inflamed glomeruli
Immune complex eposition activates complement…C5a attracts NEUTROPHILS which mediate the damage

Question 24

Poststreptococcal Glomerulonephritis

Answer 24

Nephrtic syndrome that arises 2-3 weeks after group A betahemolytic strep infection of skin or pharynx. Other organisms can cause it as well as long as they have the M PROTEIN virulence factor
Presents as hematuria, oliguria, hypertension, periorbital edema
HYPERCELLULAR and INFLAMED glomeruli
Granular IF and subepithelial humps on IM due to immune complex deposition

Question 25

Rapidly Progressive Glomerulonephritis

Answer 25

Nephritic syndrome that progresses to renal failure in weeks to months CRESECENTS composed of FIBRIN and MACROPHAGES in bowmans space DIseases include Good pasture syndrome, PGSN, diffuse proliferative glomerulonephritis, wegner granulomatosis, microscopic polyangiitis, churg-strauss syndrome and distinguish by looking at the IF pattern and other clinical signs

Question 26

Good pasture syndrome

Answer 26

Linear IF Antibody against collagen in glomerular and alveolar basement membranes Present with hematuira and hemopytysis Classcially see in young adult males can lead to Rapidly Progressive Glomerulonephritis (crescents in bowmans space)

Question 27

Poststreptococcal Glomerulonephritis IF

Answer 27

Granular. Children rarely develops to Rapidly Progressive Glomerulonephritis but 1/4 adults do (crescents in bowmans space)

Question 28

Wegner Granulomatosis

Answer 28

Negative IF c-ANCA Affects lung, kidney, and NASAL PHARYNX can lead to Rapidly Progressive Glomerulonephritis (crescents in bowmans space)

Question 29

Microscpoic Polyangitis

Answer 29

Negative IF p-ANCA can cause Rapidly Progressive Glomerulonephritis (crescents in bowmans space)

Question 30

Churg-Strauss Syndrome

Answer 30

Negative IF p-ANCA Cresents Presents with inflammation, eosinophilia, and asthma can cause Rapidly Progressive Glomerulonephritis (crescents in bowmans space)

Question 31

IgA Nephropathy/Berger Disease

Answer 31

IgA immune complex deposition is MESANGIUM of glomeruli Most common nephropathy worldwide Presents during childhood as episodic gross or microscopic hematuria w/ RBC casts, usually following a mucosal infection (since IgA production is increased in these infections) May slowly progress to renal failure

Question 32

Alport Syndrome

Answer 32

Inherited defect in type IV collagen (x-linked) See thinning and splitting of the glomerular basement membrane Presents as isolated hematuria, sensory hearing loss, and occular disturbances

Question 33

UTI

Answer 33

Most commonly arises due to a ascending infection increased incidence in females risk factors include sexual intercourse, urinary stasis, and catheters

Question 34

Cystitis + Lab findings

Answer 34

Infection of the bladder presents as dysuria, urinary frequency/urgency and suprapubic pain but systemic signs (fever) typically ABSENT Labs 1) Urinalysis = cloudy urine with >10 WBCs 2) Dipstick = positive leuokcyte esterase (due to pyuria) and nitrites (bacteria convert nitrates to nitrites) 3) Culture = GOLD standard. See greater than 100,000 colony forming units Causes include E COLI, staph saprophyticus, klebsiella pneumonia, proteus mirabilis (ALKALINE URINE w/ AMMONIA scent), and Enterococcus Faecalis

Question 35

Sterile Pyuria

Answer 35

Presence of pyuria with a negative urine culture | is highly suggestive of URETHRITIS due to chlamydia trachomatis or neisseria gonnorheae

Question 36

Pyelonephritis

Answer 36

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 the symptoms of cystitis ost commonly caused by E COLI, enterococcus faecalis, and klebsiella species

Question 37

Chronic Pyelonephritis

Answer 37

Interstitial fibrosis and atrophy of tubules due to multiple bouts of acute pyelonephritis Due to vesicoureteral reflux (children) or obstruction (BPH or cervical carcinoma) Leads to cortical scarring with blunted calyces Atrophic tubules containing eosinophilic proteinaceous material resemble thyroid follicles WAXY casts seen in urine

Question 38

Nephrolithiasis

Answer 38

Precipitation of a urinary solute as a stone risk factors include high concentration of solute in the urinary filtrate or low urine volume Presents as collicky pain with hematuria and unilateral flank tenderness

Question 39

Nephrolithiasis from calcium oxalate or calcium phosphate

Answer 39

Most common Usually from idiopathic hypercalciuria. Also seen in Chrons disease Treat with hydochlorothiazide (a Ca sparing diuretic)

Question 40

Nephrolithiasis fromammonium magnesium phosphate

Answer 40

Second Most Common Usually due to infection with urease-positive organisms (proteus vulgaris or klebsiella). Alkaline urine leads to the formation of a stone Classically results in a STAGHORN CALCULI in renal calycys that acts as a nidus for UTI. Must be surgically removed and drugs to remove bacteria

Question 41

Nephrolithiasis from Uric Acid

Answer 41

3rd most common RADIOLUCENT hot, arid climates, low urine volume, and acidic pH Also see in aptients with GOUT or HYPERURICEMIA (leukemia or myeloproliferative disroders) Treat by hydration and alkalinization of urine Give gout patients allopurinol

Question 42

Nephrolithiasis from Cysteine

Answer 42

Rare but see in CHILDREN Associated with cystinuria (a genetic defect in tubules that results in decreased reabsorption of cysteine) may form STAGHORN calculi Hydrate and alkalinize urine to treat

Question 43

Chronic Renal Failure

Answer 43

End stage kidney disease most commonly arising from diabetes mellitus, hypertension, and glomerular disease Clinical Features include 1)Uremia = increased nitrogenous waste products in blood (azotemia) that results in nausea, anorexia, pericarditis, platelet dysfunction, encephalopathy with asterixis and deposition of urea crystals in skin 2) Salt and water retention leads to hypertension 3) HYPERKALEMIA and metabolic ACIDOSIS 4) Anemia due to decreased erythropoietin production which is normally made by RENAL PERITUBULAR INTERSTITIAL CELLS 5) HYPOCALCEMIA due to decreased 1-alpha-hydroxylation of vitamin D by proximal renal tubule cells and hyperphosphatemia 6) Renal osteodystrophy from hyperparathyroidism (osteitis fibrosa cystica), osteomalacia, and osteoperosis (from metabolic acidosis) Treat with transplant or dialysis (cysts develop within SHRUNKEN kidney and increases risk for renal cell carcinoma)

Question 44

Angiomyolipoma

Answer 44

Hamartoma comprised of blood vessels, smooth muscle, and adipose tissue Increased frequency in TUBEROUS SCLEROSIS

Question 45

Renal Cell Carcinoma

Answer 45

Malignant epithelial tumor arising from kidney tubules Classic triad = HEMATURIA, palpable yellow mass with clear cytoplasm, and flank pain Also see fever, wight loss, and a variety of paraneoplastic syndromes (EPO = polycythemia, renin= hypertnesion, PTHrP = hypercalcemia, or ACTH = cushing sydnrome) Rarely can get a L sided varicocele if the tumor expands to involve the L renal vein and obsturcts drainage of L spermatic vein Due to loss of VHL tumor supressor gene leading to increased IGF-1 (growth) and HIF transcription (increases VEGF and PDGF) Sporadic = ADULT smoking MALES, unilateral, UPPER pole, Hereditary = YOUNG adults and BILATERAL. see in Von Hippel Lindau disease

Question 46

Von Hippel-Lindau Disease

Answer 46

Autosomal dominant disorder associated with inactivation of VHL gene leading to increased risk for hemangioblastoma of the cerebellum and renal cell carcinoma

Question 47

Wilms Tumor

Answer 47

Malignant kidney tumor comprised of BLASTEMA, primitive glomeruli and tubules, and stromal cells Most common in YOUNG CHILDREN Large, unilateral flank mass with hematuria and hypertension (due to renin secretion) 90% are sporadic but can also be seen in WAGR syndrome, Denys-Drash Syndrome, Beckwith-Wiedemann syndrome

Question 48

WAGR syndrome

Answer 48

``` Wilms tumor Aniridia Genital abnormalities Retardation of mental and motor Associated with DELETION of WT1 tumor supressor gene ```

Question 49

Denys-Drash Syndrome

Answer 49

Wilms tumor Pregressive renal (glomerular) disease Male pseudohermaphroditism MUTATION of WT1 tumor`

Question 50

Beckwith-Wiedemann syndrome

Answer 50

``` Wilms tumor Neonatal hypoglycemia Muscular hemihypertrophy Organomegally including tongue mutations in WT2 gene cluster ```

Question 51

Urothelial (Transitional cell) carcinoma

Answer 51

Malignant tumor arising from UROTHELIAL lining of renal pelvis, ureter, BLADDER, or urethra Risks factors includ: SMOKING, napthylamine, azo dyes, nd long term cyclophosphamide or phenacetin use OLDER adults with PAINLESS hematuria Flat pathway = HIGH grade flat tumor that then invades. EARLY p53 mutation Papillary Pathways = low grade to high grade to invasive papillary structure. no p53 association Tumors are often multifocal and reccurent ue to "field defect" = all of the lining is mutated and susceptible to developing tumor

Question 52

Squamous cell carcinoma

Answer 52

Malignant proliferation of squamous cells in background of squamous metaplasia Risk factors include 1) chronic cystitis (older women) 2) shistosoma hematobium infection (middle eastern men) 3) Long standing nephrolithiasis

Question 53

Adenocarcinoma

Answer 53

Malignant proliferation of glands, usually involving the bladder Arises from 1)Urachal remnant = tumor at dome of bladder 2) cystitis glandularis 3)exstrophy = congenital failure to form the causal portion of the anterior abdominal and bladder walls