Chapter 12 Kidney and Urinary Tract Flashcards
What is the most common congenital renal anomaly?
Horseshoe kidney
What is a horseshoe kidney?
Conjoined kidneys usually connected at the lower pole
Where are horseshoe kidneys located and what happens during development that leads to this?
Kidney is abnormally located in the lower abdomen; horseshoe kidney gets caught on the inferior mesenteric artery root during its ascent from the pelvis to the abdomen
What is renal agenesis? is it usually unilateral or bilateral?
Absent kidney formation; may be unilateral or bilateral
What does unilateral kidney agenesis lead to?
Leads to hypertrophy of the existing kidney; hyperfiltration increases risk of renal failure (specifically FSGS)
What does bilateral renal agenesis lead to?
leads to Potter Sequence; oligohydramnios with lung hypoplasia, flat face (pressed up against wall of uterus) with low set ears, and developmental defects of the extremities
Is bilateral renal agenesis compatible with life?
NO
What is dysplastic kidney? What is it characterized by? is it inheritable?
Noninherited, congenital malformation of the renal parenchyma characterized by cysts and abnormal tissue (e.g. especially cartilage)
Is Dysplastic kidney unilateral or bilateral?
Usually unilateral can be bilateral
What does bilateral dysplastic kidney need to be differentiated from?
inherited polycystic kidney disease
What is polycystic kidney disease?
Inherited defect leading to bilateral enlarged kidneys with cysts in the renal cortex and medulla
How does the AR form of PKD present?
Presents in infants as worsening renal failure and hypertension; newborns may present with Potter sequence (due to decreased amniotic fluid)
What is the AR form of PKD associated with?
Congenital hepatic fibrosis (leads to portal hypertension) and hepatic cysts
How does the AD form of PKD present?
presents in young adults as hypertension )due to increased renin), hematuria, and worsening renal failure.
What is AD PKD due to? what is it associated with?
Due to mutation in the APKD1 or APKD2 gene; cysts develop over time. It is associated with berry aneurysm (many times cause of death) hepatic cysts, and mitral valve prolapse.
What is medullary cystic kidney disease? What is its inheritance pattern?
Inherited (AD) defect leading to cysts in the medullary collecting ducts
What does medullary cystic kidney disease lead to?
Parenchymal fibrosis results in shrunken kidneys (diff than PKD) and worsening renal failure
What is acute renal failure, how fast does it develop? general
Acute, sever decrease in renal function (develops within days)
What is the hallmark of ARF?
azotemia (increase nitrogenous waste products); increased BUN and creatinine, often with oligouria.
What three categories is ARF divided into?
Prerenal, postrenal, intrarenal
What is a normal BUN:Cr?
15
What is prerenal azotemia due to?
Due to decreased blood flow to kidneys (e.g. cardiac failure); common cause of ARF
What does decreased blood flow cause in prerenal azotemia?
results in decreased GFR, azotemia, and oliguria
Describe the BUN:Cr, FENa, and urine osmolarity in prerenal azotemia?
Resorption of fluid and BUN ensues (serum BUN:Cr >15); tubular functions remains intact (Fractional excretion of sodium [FENa] 500 mOsm/kg
Describe the pathophysiology behind the BUN:Cr ration in prerenal azotemia?
Low GFR causes increased levels of aldosterone and increase Na+ absorption along with H2O. As H2O resorption increases BUN will follow. Since Creatinine cannot be reabsorb, only BUN will rise and the ratio of BUN:Cr will also rise.
What is postrenal azotemia due to? what does this result in?
Due to obstruction of urinary tract downstream from the kidney (e.g. ureters). Decreased outflow results in decreased GFR, azotemia, and oliguria.
Describe the changes in serum BUN:Cr and tubular function in the early stages of postrenal azotemia?
During the early stage of obstruction, increased tubular pressure “forces” BUN into the blood (Serum BUN:Cr >15); tubular function remains intact (FENa < 1% and urine osm > 500mOsm/kg)
Describe the changes in serum BUN:Cr and tubular function with long standing postrenal obstruction?
With long standing obstruction, tubular damage ensues, resulting in decreases reabsorption of BUN (serum BUN:Cr ratio < 15), decreased reabsorption of sodium (FENa > 2%), and inability to concentrate urine (Urine osm < 500 mOsm/kg)
What is the most common cause of acute renal failure?
Acute tubular necrosis
What happens in acute tubular necrosis? what is seen in the urine?
Injury and necrosis of tubular epithelial cells (Intrarenal). Necrotic cells plug tubules; obstruction decreases GFR. Brown, granular casts are seen in the urine
What does dysfunctional tubular epithelium result in in acute tubular necrosis?
Results in decreases reabsorption of BUN (serum BUN:Cr ratio < 15), decreased reabsorption of sodium (FENa > 2%), and inability to concentrate urine (Urine osm < 500 mOsm/kg)
What are the two possible etiologies for acute tubular necrosis?
Ischemic and Nephrotoxic
What happens in ischemic acute tubular necrosis, what is it often preceded by?
Decreased blood supply results in necrosis of the tubules. Often preceded by prerenal azotemia
What two segments of the nephron are most susceptible to ischemic damage?
Proximal tubule and medullary segment of the thick ascending limb
What happens in nephrotoxic acute tubular necrosis and which segment of the nephron is most susceptible?
Toxic agents result in necrosis of tubules. Proximal tubule is particularly susceptible.
What are 6 causes of nephrotoxic acute tubule necrosis?
1 Aminoglycosides (most common)
2 heavy metals (e.g. lead)
3 Myoglobinuria (e.g. from crush injury to muscle)
4 ethylene glycol (associated with oxalate crystals in the urine)
5 Radiocontrast dye
6 Urate (e.g. tumor lysis syndrome)
What is done before starting chemo to prevent urate mediate tubular necrosis.
Hydration and allopurinol are used prior to initiation of chemotherapy to decrease risk of urate induvced ATN
What are the clinical features of Acute tubular necrosis? 3
1 oliguria with brown, granular casts
2 Elevated BUN and Creatinine
3 Hyperkalemia (due to decreased renal excretion ) with metabolic acidosis (Decrease in organic acid secretion results in anion gap acidosis)
How is Acute tubular necrosis treated? is it reversible?
Reversible, but often requires supportive dialysis since electrolyte imbalances can be fatal.
How long does oliguria persist after treatment of acute tubular necrosis? Why?
Oliguria can persist for 2-3 weeks before recovery; tubular cells (stable cells ) take time to reenter the cell cycle and regenerate.
What is acute interstitial nephritis?
Drug-induced hypersensitivity involving the interstitium and tubules; results in acute renal failure (intrarenal azotemia)
What are three common causes for acute interstitial nephritis?
NSAIDs, Penicillin, Diuretics
How does acute interstitial nephritis present?
Presents as oliguria, fever, and rash days to weeks after starting drug; EOSINOPHILS may be seen in the urine
What is the treatment for acute interstitial nephritis?
Resolves with cessation of the drug
What can acute interstitial nephritis progress to?
renal papillary necrosis
What is renal papillary necrosis?
Necrosis of the renal papillae
How does renal papillary necrosis present?
Gross hematuria and flank pain
Name 4 possible causes of renal papillary necrosis?
1 Chronic analgesic abuse (e.g. long-term phenacetin or aspirin use)
2 Diabetes Mellitus
3 Sickle cell trait or disease
4 severe acute pyelonephritis
Describe Nephrotic syndrome, what is it characterized by (1) and what does this result in (4)
Characterized by proteinuria (> 3.5 g/day) resulting in;
1 Hypoalbuminemia - pitting edema
2 Hypogammaglobulinemia - increased risk of infection
3 hypercoaguable state - due to loss of anithrombin III
4 Hyperlipidemia and hypercholesteremia - may result in fatty casts in urine ( blood becomes “thin” so liver throws in excess fat to beef it up)
What is the most common cause of nephrotic syndrome in children?
Minimal Change Disease
What is the etiology of minimal change disease and what may it be associated with (and why)?
Usually idopathic, may be associated with hodgkin lymphoma (massive overproduction of cytokines by RS cells cause effacement of the foot processes of the podocytes)
What can be seen on histology in acute tubular necrosis?
loss of nuclei and detachment of basement membrane
What is seen on H&E stain with minimal change disease?
Normal glomeruli; lipid may be seen in proximal tubule cells.
What can be seen on EM in MCD?
Effacement of foot processes
Is there immune complex deposition in MCD, what is seen on immunofluorescence?
No immune complexes, IF is negative
Describe the selective proteinuria in MCD?
Loss of albumin but not immunoglobulin
What is the treatment for MCD and how does it respond?
Excellent response to steroids
What is the cause of damage in MCD?
Cytokines produced by T cells
What is the most common cause of nephrotic syndrome in Hispanics and African Americans?
Focal Segmental Glomerulosclerosis (FSGS)
What is the etiology of FSGS? what may it be associated with?
Usually idiopathic, may be associated with HIV, Heroin use, and sickle cell disease
What is seen on histology in FSGS?
Focal (some glomeruli) and segmental (involving only part of the glomerulus) and sclerosis (Pink) on H&E stain
What is seen on EM in FSGS?
effacement of foot processes of podocytes
Are there immune complex depositions in FSGS? what is seen on IF?
No immune complexes, IF is negative
What is the treatment for FSGS, how does it respond and what might it progress to?
Poor response to steroids; progresses to chronic renal failure.
What does MCD progress to if it does not respond to steroids?
FSGS
What is the most common cause of nephrotic disease in causcasian adults?
Membranous nephropathy
What is the etiology of membranous nephropathy and what may it be associated with?
Usually idiopathic, may be associated with Hep B or C, solide tumors, SLE, or drugs (e.g. NSAIDs and penicillamine)
What is the most common cause of death in SLE, what type?
renal failure, most common is diffuse proliferative glomerulonephritis but can also present as membranous nephropathy
What is seen on H&E stain in Membranous nephropathy?
Thick glomerular membrane
What is membranous nephropathy due to?
Due to immune complex deposition
What pattern is seen on IF with Membranous nephropathy?
Granular
What is seen on EM in membranous nephropathy?
Subepithelial deposits with ‘spike and dome’ appearance
How is membranous nephropathy treated, how does it respond, what can it progress to?
Poor response to steroids; can progress to chronic renal failure
What is seen on H&E in Membroproliferative Glomerulonephritis?
Thick glomerular BM, often with ‘tram’track’ appearance
What is Membranoproliferative glomerulonephritis due to?
immune complex deposition
What pattern is seen on IF in membranoproliferative glomerulonephritis?
granular
What causes the ‘tram track’ appearance in membranoproliferative glomerulonephritis?
Messangial cells that hold together capillary loops undergo proliferation of cytoplasm which separates the deposits
What are the two types of membranoproliferative glomerulonephritis and what are they based on?
Type I and Type II based on location of deposits
Where are deposits in Type I membranoproliferative glomerulonephritis and what is it associated with?
subendothelial; associated with HBV and HCV
Where are deposits in type II membranoproliferative glomerulonephritis and what is it associated with
Dense deposit disease; deposits located intramembanous (in BM). Associated with C3 nephritic factor
What is C3 nephritic factor?
autoantibody that stabilized C3 convertase, leading to overreaction of compliment, inflammation, and low levels of circulating C3
Which type of membranoproliferative glomerulonephritis is more often associated with ‘tram track’ appearance?
Type I
What is the treatment for membranoproliferative glomerulonephritis, how does it respond, and what may it progress to
Poor response to steroids, progresses to chronic renal failure
How does diabetes mellitus lead to glomerular damage?
High serum glucose leads to nonenzymatic glycosylation of the vascular basement membrane resulting in hyaline arteriolosclerosis.
What is affected more by NEG in DM the efferent or afferent arteriole and what does this lead to? how does this cause injury
Efferent is more affected than the afferent, leading to high glomerular filtration pressure. hyperfiltration injury leads to microalbuminuria
What is DM nephrotic syndrome characterized by?
Slcerosis of the mesangium with formation of Kimmelstiel-wilson nodules
What is the treatment for diabetic nephropathy?
ACEi slow progression of hyperfiltration-induced damage
What is the most common organ involved in systemic amyloidosis?
Kidney
How does systemic amyloidosis lead to nephrotic syndrome?
Amyloid deposits in the mesangium
What is amyloid in the kidney (or anywhere for that matter) characterized by?
Apple-green birefringence under polarized light after staining with congo red.
What are nephritic syndromes characterized by? 2 general 4 specific
Glomerular disorders characterized by glomerular inflammation and bleeding.
1 Limited proteinuria (<3.5g/day) helps differentiate from nephrotic
2 Oliguria and azotemia
3 salt retention with periorbital edema and hypertension
4 RBC Casts and dysmorphic RBCs in urine
What does biopsy reveal in in nephritic syndrome?
hypercellular, inflamed glomeruli
What mediates damage in nephritic syndrome?
Immune complex deposition activates compliment; C5a attracts neutrophils, which mediate damage
What is Poststreptococcal Glomerulonephritis (PSGN)?
Nephritic syndrome that arises after a group A beta hemolytic streptococcal infection of the skin (impetigo) or pharynx.
What types of strep strains cause PSGN and what do they carry? Can PSGN be caused by non-streptococcal organisms?
Occurs with nephritogenic strains of strep which carry M protein virulence factor. May occure after infection with nonstreptococcal organisms as well
When and how doe PSGN present? who is it usually seen in?
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
What is evident on H&E stain in PSGN?
Hypercellular, inflammed glomeruli
What mediates damage in PSGN?
immune complex deposition.
What pattern is seen on IF in PSGN?
granular
what is seen on EM in PSGN?
subepithelial humps
What is treatment for PSGN? How do children and adults respond?
Treatment is supportive. Children rarely (1%) progress to renal failure. Some adults (25%) develop rapidly progressive glomerulonephritis (RPGN)
What is Rapidly progressive glomerulonephritis?
Nephritic syndrome that progresses to renal failure in weeks to months
What is RPGN characterized on H&E?
crescents in Bowman space (of glomeruli); crescents are comprised of fibrin and macrophages
What helps to resolve the etiology of RPGN?
clinical picture and IF
What is IgA nephropathy (Berger Disease)
IgA immune complex deposition in mesangium of glomeruli
What is the most common nephropathy worldwide?
IgA nephropathy
When and how does IgA nephropathy present?
Presents during childhood as episodic gross or microscopic hematuria with RBC casts, usually following a mucosal infection (e.g. gastroenteritis) bc IgA production is increased during infection
Where is IgA deposited in IgA nephropathy?
IgA immune complex deposition in the mesangium is seen on IF
Does IgA nephropathy progress?
may progress to renal failure
What is Alport Syndrome?
Inherited defect in type IV collagen
what inheritance pattern does alport syndrome most commonly follow?
X-linked
What does Alport syndrome result in?
thinning and splitting of the glomerular BM
How does Alport disease present?
Presents as isolated hematuria, sensory hearing loss, and ocular disturbances; all are due to BM damage
What are the 3 different patterns of IF seen in RPGN?
Linear (anti-basement membrane antibody)
Granular (Immune complex deposition)
Negative IF (pauci-immune)
What disease caused RPGN with linear IF? Describe the disease
Goodpasture Syndrome; Ab against collagen in the glomerular and alveolar BM, presents as hematuria and hemoptysis, classically in young adult males
What diseases cause RPGN with granular IF?
PSGN (most common) and diffuse proliferative glomerulonephritis
What is diffuse proliferative glomerulonephritis due to?
Due to diffuse antigen antibody complex deposition, usually sub-endothelial; most common type of renal disease in SLE
What diseases cause RPGN with Negative IF? What antibodies are each associated with?
Wegner Ganulomatosis (c-ANCA), microscopic polyangiitis (p-ANCA), and Churg-Strauss syndrome (p-ANCA).
How is Churg Strauss differentiated from microscopic polyangiitis?
Churg-Strauss has granulomatous inflammation, eosinophilia, and asthma
How is Wegners differentiated from good pasture?
Sinusitis or history of nasal problems help
What is a UTI?
Infection of urethra, bladder, or kidney
What do UTIs most commonly arise due to? is there a higher incidence in males or females?
Ascending infection; increased incidence in females
What are 3 risk factors for UTIs?
sexual intercourse, urinary stasis, and catheters
What is cystitis?
Infection of the bladder
How does cystitis present?
Presents as dysuria, urinary frequency, urgency, and suprapubic pain; systemic signs (e.g. fever) are usually absent.
What are 3 common laboratory findings in cystitis?
1 Urinalysis - cloudy urine with > 10 WBCs/hpf
2 Dipstick - positive leukocyte esterase (due to pyuria) and nitrites (bacteria covert nitrates to nitrites)
3 Culture - greater than 100,000 CFU (gold standard)
What are 5 causes of cystitis and some characteristic features if any?
1 E. Coli (80%)
2 Staph Saprophyticus - increase incidence in young, sexually active women (but E. Coli is still more common)
3 Klebsiella Pneumoniae
4 Proteus mirabilis - alkaline urine with ammonia scent
5 Enterococcus Faecalis
What is sterile pyuria and what does it suggest?
the presence of pyuria (> 10 WBCs/hpf and leukocyte esterase) with a negative urine culture. It suggests urethritis due to chlamydia thracomatis or N. Gonorrhoeae ( dominant presenting sign of urethritis is dysuria)
What is pyelonephritis and what is it usually due to? what increases the risk for this
Infection of the kidney. Usually due to ascending infection: increased risk with cvesicoureteral reflux
How does pyelonephritis present?
With fever, flank pain, WBC casts, and leukocytosis in addition to symptoms of cystitis.
What causes flank pain in pyelonephritis?
Inflammation results in sensitization of the nerves of the capsule of the kidney
What causes WBC casts in pyelonephritis?
When infection ascends from ureter into kidney it going to be walking its way up the tubule, which results in inflammatory cells in the tubule which for casts
What are the 3 most common pathogens for pyelonephritis?
1 E. Coli (90%)
2 Enterococcus Faecalis
3 Klebsiella species
What is Chronic pyelonephritis?
Interstitial fibrosis and atrophy of tubules due to multipple bouts of acute pyelonephritis
What is chronic pyelonephritis due to?
Due to vesicoureteral reflux (children) or obstruction (e.g. BPH or cervical carcinoma)
What does chronic pyelonephritis lead to?
Cortical scarring with blunted calyces; scarring at upper and lower poles is characteristic of vesicoureteral reflux.
What microscopic change occurs in tubules in chronic pyelonephritis?
Atrophic tubules containing eosinophilic proteinaceous material resemble thyroid follicles (‘thyroidization’ of kidney): waxy casts may be seen in urine
What is nephrolithiasis?
Precipitation of a urinary solute as a stone
What are two risk factors for nephrolithiasis?
High concentration of solute in urinary filtrate and low urine volume
How does nephrolithiasis present? how does it resolve?
colicky pain with hematuria and unilateral flank tenderness. Stone usually passd within hours; if not, surgical intervention may be required
What is Chronic renal failure and what are 3 things it may result from?
End stage kidney disease. May result from glomerular, tubular, inflammatory, or vascular insults
What are the most common causes of chronic renal failure?
DM, HTN, and glomerular disease
What are 6 clinical features of CRF, and what they each result in
1 Uremia - increased nitrogenous waste products in blood (azotemia) results in nausea, anorexia, pericarditis, platelet dysfunction, encephalopathy with asterixis, and deposition of urea crystals in the skin
2 Salt and water retention with resultant HTN
3 Hyperkalemia with metabolic acidosis (anion gap)
4 anemia due to decreased EPO production by renal peritubular cells
5 Hypoclalcemia due to decreased 1 alpha hydroxylation of Bit D by proximal tubule cells and hyperphosphstemia (free phosphate will bing with calcium contributing to further hypocalcemia)
6 Renal osteodystrophy due to secondary hyperparathyroidism , osteomalacia, and osteoporosis
What is asterixis?
tremor of hand when wrist is extended
What causes platelet dysfunction in uremia?
uremia inhibits platelet adhesion and aggregation
What causes secondary hyperparathyroidism in CRF?
Osteo fibrosa cystica - hypocalcemia causes PTH to rise and resorption of calcium burns out bone and causes fibrosis and cysts
How does CRF lead to osteoporosis?
Metabolic acidosis is buffered against the bone which slowly leeches calcium.
What does treatment of CRF involve? what often happens as a result of treatment?
Treatment involves dialysis or renal transplant. Cysts often develop with shrunken end stage kidneys during dialysis, increasing risk for RCC
What are the four major types of kidney stones?
1 Calcium oxalate and/or calcium phosphate
2 Ammonium magnesium phosphate
3 Uric acid
4 Cystine
Describe the frequency of the different types of kidney stones?
Calcium - most common type: usually seen in adults
amp- second most common type
uric acid - third most common stone (5%); radiolucent (as opposed to other types which are radiopaque
Cystine - rare cause of nephrolithiasis; most commonly seen in children
What are the causes of calcium stones?
most common cause is idiopathic hypercalcuria; hypercalcemia and its related causes must be excluded. Also seen with Crohn disease (Small bowel damage can cause increased absorption of oxalate which can bind Ca2+
What are the causes of AMP stones
Most common cause is infection with urease positive organisms (proteus vulgaris or Klebsiella); alkaline urine leads to formation of stones
What are the causes of uric acid stones?
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) increase risk.
What are the causes of cysteine stones?
Associated with cystinuria (a genetic defect of tubules that results in decreased reabsorption of cysteine)
What is the treatment of calcium stones?
Treatment is hydrochlorothiazide (calcium sparing diuretic)
What is a common complication of AMP stones
Classically, results in staghorn calculi in renal calyces, which act as a nidus for UTIs.
What is the treatment for AMP stones?
Treatment involves surgical removal of stone (due to size) and eradication of pathogen (to prevent recurrence).
What is the treatment of uric acid stones?
Treatment involves hydration and alkalinization of urine (Potassium bicarb); allopurinol is also administered in patients with gout. Acidic pH aids in formation of this type of stone
What is a possible complication of cysteine stones and what does treatment involve?
may form staghorn calculi; treatment involves hydration and alkalinization of urine
What is an angiomyolipoma?
Hamartoma comprised of blood vessels, smooth muscle, and adipose tissure
Increased frequency of angiomyolipoma is seen in what disease?
Tuberous sclerosis
What is renal cell carcinoma and where does it arise from?
Malignant epithelial tumor arising from kidney tubules
What is the classic presenting triad of RCC?
hematuria, palpable mass, and flank pain
Does the triad of RCC commonly occur together? what is the most common?
no, hematuria is the most common
What other symptoms may be present in RCC?
Fever, weight loss, or paraneoplastic syndrome (e.g. EPO, renin, PTHrP, or ACTH) may also by present
What is a rare presentation of RCC?
Left sided varicolcele. Involvement of th eleft renal vein by the carcinoma blocks the drainage of the left spermatic vein leading to varicocele. The right spermatic vein drains directly into the IVC; hence, right sided varicolcele is not seen
What does gross and microscopic examination show in RCC?
Gross exam reveals a yellow mass; microscopically, the most common variant exhibits clear cytoplasm (clear cell type)
Describe the pathogenesis of RCC?
Pathogenesis involve the loss of VHL (3p) tumor suppressor gene, which leads to increased IGF-1 (promotes growth) and increased HIF transcription factor (increases VEGF and PDGF)
Describe how sporadic RCC tumors arise? what is the greatest risk factor?
classically arise in adult males (average age is 60) as a single tumor in the upper pole of the kidney; major risk factor for sporadic tumors is cigarette smoke
Describe how hereditary RCC tumors arise?
arise in younger adults and are often bilateral. VHL disease is an AD disorder associated with inactivation of the VHL gene leading to increased risk for hemangioblastoma of the cerebellum and RCC.
Describe the staging of RCC? T and N
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
What is a Wilms Tumor?
Malignant kidney tumor comprised of blastema (immature kidney mesenchyme), primitive glomeruli and tubules, and stromal cells.
What is the most common renal tumor in children and what is the average age?
Wilms tumor, average age is 3
How does a Wilms tumor present?
Presents as a large, unilateral flank mass with hematuria and hypertension (due to renin secretion)
What percent of Wilms tumors are sporadic and what percent are associated with syndromes?
90% sporadic 10% syndrome
What are three syndromes in which Wilms tumors can be seen?
WAGR syndrome
Denys-Drash syndrome
Beckwith-Wiedemann syndrome
What is WAGR syndrome?
Wilms tumor Aniridia Genital abnormalities Retardation; mental and motor associated with deletion of WT1 tumor suppressor gene
What is Denys-Drash Syndrome?
Wilms tumor, progressive renal (glomerular) disease, and male pseudohermaphroditism; associated with mutations of WT1
What is Beckwith-Wiedemann syndrome?
Wilms tumor, neonatal hypoglycemia, muscular hemihypertropy, and organomegaly (including tongue); associated with mutations in WT2 gene cluster (imprinted genes on cr11), particularly IGF-2
What is Urothelial (transitional cell) carcinoma?
malignant tumor arising from the urothelial lining of the renal pelvis, ureter, bladder, or urethra.
What is the most common type of lower urinary tract cancer, and where does it usually arise?
Urothelial (transitional cell) carcinoma, usually arises in the bladder
What are the major risk factors for Urothelial (transitional cell) carcinoma?
Major risk factor is cigarette smoke; aditional risk factors are naphthylamine, azo dyes (hair coloring), and long term cyclophosphamide or phenacetin use
Who is Urothelial carcinoma generally seen in? How does it classically present?
generally seen in older adults; classically presents with painless hematuria
What are the two distinct pathways by which urothelial carcinoma can arise?
Flat and papillary
Describe flat urothelial carcinoma?
develops as a high grade flat tumor and then invades; associated with early p53 mutations
Describe Papillary urothelial carcinoma?
develops as a low grade papillary tumor that progresses to a high grad papillary tumor and then invades; not associated with early p53 mutations
Describe the involvement of urothelial carcinomas
Tumors are often multifocal and recur (‘field defect’ entire field is mutated due to chronic exposure to carcinogens)
What is Squamous cell carcinoma and where does it most commonly arise along the urinary tract?
Malignant proliferation of squamous cells, usually involving the bladder
How does SCC of the bladder usually arise?
Arises from a background of squamous cell metaplasia (normal bladder surface is not lined by squamous epithelium)
What are the risk factors for bladder SCC?
Risk factors included chronic cystitis (older women),
schistosoma hematobium infection (middle eastern male, embeds itself in bladder wall and causes chronic inflammation),
long standing nephrolithiasis
What is adenocarcinoma and which part of the urinary tract does it most commonly involve?
malignant proliferation of glands, usually involving bladder
What does adenocarcinoma of the urinary tract arise from?
Arises from urachal remnant (tumor develops at the DOME of the bladder), cystitis glandularis (chronic inflammation resulting in columanar metaplasia), or exstrophy
what is exstrophy of the bladder?
Congenital failure to form the caudal (lower) portion of the anterior abdominal and bladder walls, which exposes the bladder surface to the outside world.
What is the urachus?
Duct that connects the fetal bladder with the yolk sac and allows bladder to drain waste into the yolk sac. normally runs through dome of the bladder through umbilical cord and is lined by glandular cells (which are not normally present in the bladder). failure to involute can leave remnants which may become adenocarcinoma.
