Kidney and Urinary Tract Pathology Flashcards
WAGR syndrome is associated with ________
Deletion of WT1 tumor suppressor gene (located at 11p13)
Which drugs can causes membranous nephropathy?
NSAIDs
Penicillamine
Results of hypogammaglobulinemia seen in nephrotic syndrome
Increased risk of infection
How does Wilms tumor present?
Large, unilateral flank mass with hematuria and HTN (due to renin secretion)
Most common pathogens of pyelonephritis
E coli
Enteroccoccus faecalis
Klebsiella
Results of hypoalbubinemia seen in nephrotic syndrome
Pitting edema
Alkaline urine with ammonia scent
Proteus mirabilis
poststreptococcal glomerulonephritis on H&E
hypercellular, inflamed glomeruli
Hamartoma comprised of blood vessels, smooth muscle, and adipose tissue
Angiomyolipoma
___________ and ____________ are used prior to initiation of chemotherapy to decrease risk of urate-induced acute tubular necrosis.
Hydration; allopurinol
Paraneoplastic syndromes associated with renal cell carcinoma
EPO
Renin
PTHrP
ACTH
Risk factors for uric acid stones
Hot, arid climates, low urine volume, and acidic pH
Where does the tumor develop in adenocarcinoma that arises from a urachal remnant?
Dome of the bladder
Inherited defect leading to bilateral enlarged kidneys with cyst in the renal cortex and medulla
Polycystic kidney disease
Histo of chronic pyelonephritis
Atrophic tubules containing eosinophilic proteinaceous material resemble thyroid follicles
Denys-Drash syndrome
- Wilms tumor
- Progressive renal (glomerular) disease
- Male pseudohermaphroditism
Sterile pyuria suggests urethritis due to ____________ or ___________.
Chlamydia or Neisseria gonorrhoeae
*Dominant presenting sign of urethritis is dysuria
Types of acue renal failure
Prerenal
Postrenal
Intrarenal
Clinical features of uremia
Increased nitrogenous waste products in blood (azotemia) results in nausea, anorexia, pericarditis, platelet dysfunction, encephalopathy with asterixis, and deposition of urea crystals in skin
Nephritic syndrome that arises after group A B-hemolytic streptococcal infection of the skin or pharynx
Poststreptococcal glomerulonephritis
Which causes of rapidly progressive glomerulonephritis present with a linear IF pattern
Goodpasture syndrome
How does a renal cell carcinoma result in left-sided varicocele?
Involvement of the left renal vein by carcinoma blocks drainage of the left spermatic vein leading to varicocele
*Right spermatic vein drains directly into the IVC; hence, right-sided varicocele is not seen
Long term results on medulalry cystic kidney disease
Parenchymal fibrosis results in shrunken kidneys and worsening renal failure
Classic presentation of ammonium magnesium phosphate stone
Staghorn calculi in renal calyces
Cystine stones are associated with _______.
Cystinuria
- A genetic defect of tubules that results in decreased reabsorption of cysteine
Nephritic syndrome that progresses to renal failure in weeks to months
Rapidly progressive glomerulonephritis
Most common cause of nephrotic syndrome in Hispanics and AA
Focal segmental glomerulosclerosis
Causes of nephrotoxic acute tubular necrosis
Aminoglycosides
Heavy metals
Myoglobinuria
Ethylene glycol (associated with oxalate crystals in urine)
Radioconstrast dye
Urate (tumor lysis syndrome)
Conjoined kidneys usually connected at the lower pole
Horseshoe kidney
Autosomal dominant PKD is associate with _________, ________, and _________.
Berry aneurysm,hepatic cysts, and mitral vale prolapse
Gross and microscopic of renal cell carcinoma
Yellow mass; microscopically, the most common variant exhibits clear cystoplasm
Beckwith-Wiedemann syndrome is associated with ____________.
Mutations in WT2 gene cluster (imprinted genes at 11p15.5), particularly IGF-2
How does IgA nephropathy present?
Episodic gross or microscopic hematuria with RBC casts, usually following mucosal infections
Cysts often develop witin shrunken end-stage kidneys during dialysis, increasing the risk for ____________.
Renal cell carcinoma
How does cystitis present?
Dysuria
Urinary frequency
Urgency
Suprapubic pain
*Systemic signs are usually absent
BUN: Cr ratio, FENa, and urine osmolality in prerenal azotemia
BUN: Cr ratio> 15
[FENa]<1%
Urine osmolality >500
How does alport syndrome present?
Isolated hematuria, sensory hearing loss, and ocular disturbances
EM of membranous nephropathy
Subepithelial depositis with “spike and dome” appearance on EM due to immune complex deposition
Beckwith-Wiedemann syndrome
- Wilms tumor
- Neonatal hypoglycemia
- Muscular hemihypertrophy
- Organomegaly (including tongue)
Risk factors of sqaumous cell carcinoma of the bladder
- Chronic cystitis (older women)
- Shistosoma haematobium infection (Egyptian male)
- Long-standing nephrolithiasis
EM of poststreptococcal glomerulonephritis
Supportive
- Children rarely progress to renal failure
- Some adults develop rapidly progressive glomerulonephritis
Treatment for uric acid stones
Treatment involves hydration and alkalinization of urine (potassium bicarbonate); allopurinol is also administered in patients with gout.
Selective proteinuria is seen in __________.
Minimal change disease
*Loss of albumin, but not immunoglobulin
Injury and necrosis of tubular epithelial cells
Acute tubular necrosis (intrarenal azotemia)
Why is hypocalcemia a clinical feature of chronic renal failure?
Due to decreased 1-alpha hydroxylation of vitamin D by proximal renal tubule cells and hyperphosphatemia
Most common malignant renal tumor in children
Wilms tumor
IgA nephropathy results in immune complex deposition in _________ of glomeruli.
Mesangium
Cuase of acute tubular necrosis
Necrotic cells plug tubules; obstruction decreases GFR
*Brown, granular casts are aseen in the urine
Goodpasture’s syndrome
Antibody against collagen in glomerular and alveolar basement membranes; presents as hematuria and hemoptysis classically in young, adult males
Treatment for a calcium oxalate and/ or calcium phosphate stone
HCTZ (calcium-sparing diueretic)
Major way in which uric acid stones differ from other types of stones
Radiolucent
Which parts of the kidney are particularly susceptible to ischemic damage?
Proximal tubule and medulalry segment of the thick ascending limb
Cuases of renal papillary necrosis
Chronic analgesic abuse (long term-phenacetin or aspiring use)
Diabetes mellitus
Sickle cell trait or disease
Severe acute pyelonephritis
Histo of membranous nephropathy
Thick glomerular basement membrane
Chronic pyelonephritis
Interstitial fibrosis and atrophy of tubules due to multiple bouts of acute pyelonephritis
BUN: Cr ratio, FENa, and urine osmolality in postrenal azotemia
Early
- BUN: Cr ratio> 15
- [FENa]<1%
- Urine osmolality >500
Long-standing
- BUN: Cr ratio<15
- [FENa]> 2%
- Urine osmolality<500
Why is renal osteodystrophy a clinical feature of chronic renal failure?
Due to secondary hyperparathyroidism, osteomalacia, and osteoporosis
How does urothelial carcinoma?
Generally seen in older adults; clasically presents with painless hematuria
Chronic pyelonephritis leads to…
Cortical scarring with blunted calyces; Scarring at upper and lower poles is characteristic of vesicoureteral reflux
How does acute intersitial nephritis present?
Oliguria, fever, and rash days to weeks after starting a drug; eosinophils may be seen in urine
How is rapidly progressive glomerulonephritis characterized?
Crescents in Bowman space on H&E stain; crescents are comprised of fibrin and macrophages
Clinical features of acute tubular necrosis
- oliguria with brown, granular casts
- Elevated BUN and creatinine
- Hyperkalemia with metabolic acidosis
What increases the risk for pyelonephritis?
Vesicoureteral reflux
How does autosomal recessive form of polycystic kidney disease present?
In infants as worsening renal failure and hypertension; newborns may present with Potter sequence
Hallmark of acute renal failure
Azotemia (increased BUN and creatinine), often with oliguria
Ischemia leading to acute tubular necrosis is often preceded by ____________.
Prerenal azotemia
Histo of membranoproliferative glomerulonephritis
Thick glomerular basement membrane on H&E often with “tram-track” appearance
There is an increased risk of angiomyolipoma in ___________.
Tuberous sclerosis
Cause of postrenal azotemia
Due to obstruction o furinary tract downstream from the kidney
in nephrotic syndrome, proteinuria must be > ___________g/day.
3.5
Biopsy of nephritic syndrome
Hypercellular, inflamed glomeruli
Is acute tubular necrosis reversible?
Reversible, but often requires supportive dialysis since electroclyte imbalances can be fatal
*oliguria can persist for 2-3 wks before recovery; tubular cells take time to reenter the cell cycle and regenerate
BUN: Cr ratio, FENa, and urine osmolality in intrarenal azotemia
- BUN: Cr ratio<15%
- [FENa]>2%
- Urine osmolality <500
How does renal cell carcinoma present?
Hematuria, palpable mass, and flank pain
*All three symptoms rarely occur together
How does renal papillary necrosis present?
Gross hematuria and flank pain
Flat pathway of urothelial carcinoma development
- Develops as a hig-grade papillary tumor and then invades
- Associated with early p53 mutations
Most common causes of chronic renal failure
DM, HTN, and glomerular disease
Cause of prerenal azotemia
Due to decreased blood flow to kidneys.
Results of unilateral kidney agenesis
Hypertrophy of the existing kidney; hyperfiltration increases risk of renal failure later in life
Most common type of lower urinary tract cancer
Urothelial (Transitional cell) carcinoma
Causes of rapidly progressive glomerulonephritis
Goodpasture syndrome
PSGN or diffuse proliferative glomerulonephritis
Wegener granulomatosis
Microscopic polyangiitis
Churg-strauss syndrome
Causes of nephrolithiasis in order of frequency
Calcium oxalate and/or calcium phosphate
Ammonium magnesium phosphate
Uric acid
Cystine
Malignant kidney tumor comprised of blastema, primitive glomeruli and tubules, and stromal cells
Wilms tumor
Pathophysiology of nephrotic syndrome causes by DM
- Nonenzymatic glycosylation of the vascular basement membrane resulting in hyalin arteriolosclerosis
- Glomerular efferent arteriole is more affected than the afferent arteriole, leading to high glomerular filtration pressure
- Hyperfiltration leads to microalbuminuria
- Eventual progression to nephrotic syndrome
Characteristics of sporadic renal cell carcinomas
- Classically arise in adult males as a single tumor in the upper pole of the kidney
- Risk factor: cigarette smoke
Drug-induced hypersensitivity involving the interstitium and tubules; results in acute renal failure
Acute intersitital nephritis
Pathogenesis of renal cell carcinoma
- Loss of VHL tumor suppressor gene, which leads to increased IGF-1 and increased HIF transciption factor (increases VEGF and PDGF)
Why is a hypercoagulable state seen in nephrotic syndrome?
Due to loss of antithrombin III
Autosomal recessive PKD is associated with _______ and __________.
Congenital hepatic fibrosis (leads to portal hypertension) and hepatic cysts
How does nephrolithiasis present?
As colicky pain with hematuria and unilateral flank tenderness
Which disease result in granular IF patterns?
Poststreptococcal glomerulonephritis or diffuse proliferative glomerulonephritis
Findings in urine in chronic pyeloenephritis
Waxy casts
Nephrotic syndrome
- Glomerular disorders characterized by proteinuria resulting in:
- Hypoalbuminemia
- Hypogammaglobulinemia
- Hypercoagulable state
- Hyperlipidemia and hypercholesterolemia
Acute interstial nephritis may progress to ________.
Renal papillary necrosis
How does poststreptococcal glomerulonephritis present
2-3 wks after infection as hematuria (cola-colored urine), oliguria, HTN, and periorbital edema
Calcium oxalate and/ calcium phosphate stones can be seen with _________.
Chrohn disease
Causes of nephrotic syndrome
Minimal change disease
Focal segmental glomerulosclerosis
Membranous nephropathy
Membranoproliferative glomerulonephritis
Diabetes mellitus
Systemic amyloidosis
Clinical features of chronic renal failure
Uremia
Salt and water retention with resultant HTN
Hyperkalemia with metabolic acidosis
Anemia
Hypocalcemia
Renal osteodystrophy
Focal segmental glomerulosclerosis may be associated with __________, __________, and __________.
HIV; heroin use; sickle cell disease
most common type of renal disease in SLE
Diffuse proliferative glomerulonephritis
Treatment for cystine stones
May form staghorn calculi; treatment involves hydration and alkalization of urine
EM of focal segmental glomerulosclerosis
Effacement of foot processes
Causes of UTI
- E. Coli
- Staph saprophyticus
- Increased incidence in young, sexually active women
- Klebsiella
- Proteus mirabilis
- Enterococcus faecalis
membranoproliferative glomerulonephritis type I (subendothelial) is associated with ______ and _________.
HBV; HCV
Alport syndrome
- Inherited defect in type IV collagen; most commonly X-linked
- Results in thinning and splitting of the glomerular basement membrane
Electron microscopy of minimal change disease
Effacement of foot processes
Which causes of rapidly progressive glomerulonephritis have a negative IF?
Wegener granulomatosis
Microscopic polyangiitis
Churg-Strauss syndrome
Denys-Drash syndrome is associated with ___________.
Mutations of WT1
Treatment for chronic renal failure
Dialysis or renal transplant
Damage seen in minimal change disease is mediated by _________.
Cytokines from T cells
Causes of acute interstitial nephritis
NSAIDs
Penicillin
Diuretics
WAGR syndrome
- Wilms tumor
- Aniridia
- Genital abnormalities
- Mental and motor Retardation
Why is anemia a clinical feature of chronic renal failure?
Due to decreased erythropoietin production by renal peritubular interstitial cells
Histo of minimial change disease
Normal glomeruli on H &E stain; lipid may be seen in proximal tubule cells
Membranous nephropathy may be associated with _________, __________, _________, or __________.
Hep b or C
solid tumors
SLE
Drugs
Minimal change disease is associated with ___________.
Hodgkin lymphoma
Pathophysiolofy of prerenal azotemia
- Decreased blood flow results in decreased GFR, azotemia, and oliguria
- Reabsorption of fluid and BUN ensues (serum BUN: Cr ratio>15)
- Tubular function remains intact
___________ slow progression hyperfiltration induced damage.
ACE inhibitors
Horseshoe kidney is abnormally located in the lower abdomen because it gets caught on the _______________ during its ascent from the pelvis to the abdomen.
Inferior mesenteric artery
Amyloid deposits in the _______, resulting in nephrotic syndrome.
Mesangium
Papillary pathway of urothelial carcinoma development
- Develops as a low-grade papillary tumor that progresses to a high-grade papillary tumor and then invades
- Not associated with early p53 mutations
Characteristics of nephrotic syndrome due to DM
Sclerosis of the mesangium with formation of Kimmelstiel-Wilson nodules
Exstrophy
Congenital failure to form the caudal portion of the anterior abdominal and bladder walls
Most common cause of nephrotic syndrome in Caucasian adults
Membranous nephropathy
UTI risk factors
Sexual intercouse
Urinary stasis
Catheters
Results of hyperlipidemia and hypercholesterolemia seen in nephrotic syndrome
May result in fatty casts in urine
Pathophysiology of postrenal azotemia
- Decreased outflow results in decreased GFR, azotemia, and oligouria
- During early stage of obstruction, increased tubular pressure “forces” BUN into the blood; tubular function remains intact
- With long-standing obstructuion, tubular damage ensures, resulting in decreased reabsorption of BUN, decreased absorption of sodium, and inability to concentrate urine
membranoproliferative glomerulonephritis type II (intramembranous) is associated with ______ .
C3 nephritic factor
- Autoantibody that stabilizes C3 convertase, leading to overactivation of complement, inflammation, and low levels of circulating C3
Laboratory findings of cystitis
Urinalysis
- Cloudy urine with >10 WBCs/ high power field
Dipstick
- Positive leukocyte esterase (due to pyuria) and nitrites
Culture
- Greater than 100,000 colony forming units
____________,_________, and _________ distinguish Chrug-Strauss from microscopic polyangiitis.
Granulomatous inflammation, eosinophilia, and asthma
Nephrtic syndrome
Glomerular disorders characterized by glomerular inflammation and bleeding
- Limited proteinuria (<3.5 g/day)
- Oliguria and azotemia
- Salt retention wth periorbital edema and HTN
- RBC casts and dysmorphic RBCs in urine
Most common cause of ammonium magnesium phosphate stone
Infection with urease postive organisms (proteus vulgaris or Klebsiella); alkaline urine leads to formation of urine
Adenocarcinoma of the bladder arises from..
- Urachal remnant
- Cystitis glandularis
- Exstrophy
Characteristics of hereditary renal cell carcinomas
- Von Hippel-Lindau
- Autosomal dominant
- Inactivation of the VHL gene leading to increased risk for hemangioblastoma of the cerebellum and renal cell carcinoma
How does pyelonephritis present?
Fever
Flank pain
WBC casts
leukocytosis, in addition to symptoms of cystitis
Treatment for ammonium magnesium phosphate stone
Surgical removal of stone (due to size) and eradication of pathogen (to prevent recurrence)
Causes of nephritic syndrome
Poststreptococcal glomerulonephritis
Rapidly progressive glomerulonephritis
IgA nephropathy (berger disease)
Alport syndrome
Potter sequence
Bilateral agenesis leads to oligohydramnios with lung hypoplasia, flat face with low set ears, and developmental defects of the extremities; incompatible with life
Which cause of nephrotic syndrome has an excellent response to steroids?
Minimal change disease
How does the autosomal dominant form of PKD presnt?
In young adults as HTN (due to increased renin), hematuria, and worsening renal failure
Cause of chronic pyelonephritis
Due to vesicoureteral reflux (children) or obstruction (e.g. BPH or cervical carcinoma)
Pathophysiology of nephritic syndrome
Immune-complex deposition activates complement; C5a attracts neutrophils, which mediate damage
Inherited (autosomal dominant) defect leading to cysts in the medullary collecting ducts
Medullary cystic kidney diasease
Risk factors for urothelial (transitional cell) carcinoma
- Cigarette smoke (major)
- Napthylamine
- Azo dyes
- Long-term cyclophosphamide or phenacetin use
Dysplastic kidney disease
non-inherited, congenital malformation of the renal parenchyma characterized by cysts and abdnormal tissue
*Usually unilateral; when bilateral, must be distinguised from inherited polycystic kidney disease
Which part of the kidney is most susceptible to nephrotoxic acute tubular necrosis?
Proximal tubules
Most common cause of nephrotic syndrome in children
Minimal change disease
