Renal Pathology Flashcards
Most common congenital renal anomaly in which there is conjoined kidneys usually connected at the lower pole due to restricted ascension by inferior mesenteric artery
Horseshoe kidneys
Unilateral renal agenesis leads to _______ of existing kidney. _______ increases the risk of renal failure later in life
Hypertrophy; hyperfiltration
Bilateral renal agenesis is incompatible with life and is associated with oligohydramnios. What are the consequences of oligohydramnios?
Lung hypoplasia, flat face with low set ears, and developmental defects of extremities (Potter sequence)
Noninherited, congenital malformation of renal parenchyma characterized by cysts and abnormal tissue (e.g., cartilage)
Dysplastic kidney
[Important to note that this is NOT an inherited disorder!]
T/F: dysplastic kidney is most commonly unilateral
True
NOTE — when it is bilateral, it must be distinguished from inherited polycystic kidney disease
Inherited renal defect resulting in bilateral enlarged kidneys with cysts in renal cortex and medulla
Polycystic kidney disease
The _____ ______ inheritance pattern of PKD presents in infancy with worsening renal failure and HTN. Newborns may present with Potter sequence. This condition is associated with congenital _______ fibrosis and _______ cysts
Autosomal recessive; hepatic; hepatic
The ______ ______ inheritance pattern of PKD presents in young adults with HTN, hematuria, and worsening renal failure (with increased plasma renin). It is caused by a mutation in the ____ or ______ gene and cysts develop over time
Autosomal dominant; APKD1; APKD2
3 associations with autosomal dominant PKD
Berry aneurysm
Hepatic cysts
Mitral valve prolapse
Medullary cystic kidney disease is a ______ _______ inherited defect leading to cysts in medullary collecting ducts. ________ fibrosis results in shrunked kidneys and worsening renal failure
Autosomal dominant; parenchymal
Acute renal failure is defined as acute, severe decrease in renal function. The hallmark is ________, often with oliguria. It is divided into prerenal, postrenal, and intrarenal based on etiology
Azotemia
increase in nitrogenous waste products in the blood — measured as BUN/Cr
Cause of prerenal azotemia
Decreased blood flow to kidneys
Decreased blood flow to the kidney leads to prerenal azotemia which manifests as azotemia and oliguria. How does this alter the GFR, BUN:Cr, FeNa, and urine osmolality?
Decreased GFR
Increased BUN:Cr (>15-20 — due to increase in reabsorption of fluid and BUN)
FENa <1% and Urine osmolality >500 (kidneys retain ability to concentrate the urine)
What causes postrenal azotemia?
Obstruction of urinary tract downstream from kidney
How does postrenal azotemia alter the GFR, BUN:Cr, FeNa, and urine osmolality in the EARLY stages?
GFR Decreases
Serum BUN:CR increases (>15) — due to increased tubular pressure
FeNA <1%, urine osmolality >500 — kidneys retain ability to concentrate the urine
How does postrenal azotemia alter the BUN:Cr, FeNa, and urine osmolality in the LATE stages in the case of longstanding obstruction and tubular damage?
BUN:Cr decreases (<15) due to decreased reabsorption
FENa >2% due to decreased reabsorption
Urine osmolality <500 — inability to concentrate urine!
Most common cause of acute renal failure
Acute tubular necrosis — causes injury and necrosis of tubular epithelial cells
How does ATN cause acute renal failure?
Necrotic tubular epithelial cells plug the tubules — obstruction decreases GFR
Brown granular casts are seen in the urine
How does acute tubular necrosis alter the GFR, BUN:Cr, FeNa, and urine osmolality in the EARLY stages?
Decreased GFR
Decreased reabsorption of BUN —> BUN:Cr <15
Decreased reabsorption of sodium —> FENa >2%
Inability to concentrate urine —> urine osmolality <500
2 major etiologies of acute tubular necrosis
Ischemic (often preceded by prerenal azotemia; proximal tubule and medullary segment of thick ascending limb are particularly susceptible)
Nephrotoxic (toxic agents result in necrosis of tubules; proximal tubule is particularly susceptible)
Causes of nephrotoxic ATN
Amingoglycosides Heavy metals (e.g., lead) Myoglobinuria (e.g., crush injury) Ethylene glycol (present with oxalate crystals) Radiocontrast dye Urate (e.g., tumor lysis syndrome)
Clinical features of ATN include oliguria with brown granular casts, elevated BUN and creatinine, and what electrolyte/acid-base disturbance?
Hyperkalemia with high anion gap metabolic acidosis
[decreased renal excretion of potassium and organic acids]
T/F: ATN is reversible, but often requires supportive dialysis since electrolyte imbalances can be fatal
True
Oliguria can persist for 2-3 weeks before recovery because tubular cells (stable cells) take time to reenter cell cycle and regenerate)
Drug-induced HSR of interstitium and tubules, resulting in intrarenal acute renal failure
Acute interstitial nephritis
Causes of acute interstitial nephritis
NSAIDs
PCN
Diuretics
Clinical presentation of acute interstitial nephritis includes oliguria, fever, and rash days to weeks after starting the offending drug. ______ may be seen in the urine. Symptoms resolve with cessation of drug, however they may also progress to ______ ______ ______
Eosinophils; renal papillary necrosis
Clinical features of renal papillary necrosis
Gross hematuria
Flank pain
Causes of renal papillary necrosis
Chronic analgesic abuse (e.g., long term phenacetin or ASA use)
Diabetes mellitus
Sickle cell trait or disease
Severe acute pyelonephritis
Which one is characterized by proteinuria >3.5g/day — nephritic syndrome or nephrotic syndrome?
Nephrotic syndrome
Nephrotic syndromes are characterized as glomerular disorders with proteinuria >3.5g/day. What are the other features of nephrotic syndromes?
Hypoalbuminemia
Hypogammaglobulinemia (increased risk of infection)
Hypercoagulable state (loss of antithrombin III)
Hyperlipidemia and hypercholesterolemia
Most common cause of nephrotic syndrome in children
Minimal change disease
Minimal change disease is usually idiopathic, but may be associated with _____ lymphoma
Hodgkin
Minimal change disease findings on H and E stain, EM, and IF
H and E = Normal glomeruli, lipid may be seen in PCT cells
EM = effacement of foot processes
IF = negative — no immune complex deposits
Minimal change disease exhibits selective proteinuria, so there is loss of ______, but not immunoglobulin
Albumin
Tx for minimal change disease
Excellent response to steroids (damage is mediated by cytokines from T cells)
Most common cause of nephrotic syndrome in hispanics and african americans; usually idiopathic but may be associated with HIV, heroin use, and sickle cell disease
FSGS
FSGS findings on H and E, EM, and IF
H and E = focal and segmental sclerosis
EM = effacement of foot processes
IF = negative — no immune complex deposition
T/F: FSGS has an excellent response to steroids
False — it has a poor response to steroids; often progresses to chronic renal failure
Most common cause of nephrotic syndrome in Caucasian adults. Usually idiopathic but may be associated with hepatitis B or C, solid tumors, SLE, or drugs (e.g., NSAIDs and penicillamine)
Membranous nephropathy
Membranous nephropathy findings on H and E, EM, and IF
H and E = thick glomerular basement membrane
EM = subepithelial deposits with ‘spike and dome’ appearance
IF = granular due to immune complex deposition
Membranoproliferative glomerulonephritis findings on H and E and IF
H and E = thick capillary membranes with ‘tram-track’ appearance
IF = granular due to immune complex deposition
Membranoproliferative glomerulonephritis is divided into 2 types based on location of the deposits. What are the 2 types and their disease associations?
Type I = subendothelial — associated with HBV and HCV
Type II = intramembranous — associated with C3 nephritic factor (stabilizes C3 convertase, potentiates complement activation and inflammatory damage)
Which is more often associated with tram-track appearance on H and E — Type I or Type II membranoproliferative glomerulonephritis?
Type I
T/F: membranoproliferative glomerulonephitis can cause nephritic syndrome, nephrotic syndrome, or both
True
How does diabetes mellitus lead to nephrotic syndrome?
High serum glucose leads to non-enzymatic glycosylation of vascular basement membranes, resulting in hyaline arteriolosclerosis
Efferent arteriole is more affected than afferent arteriole, leading to high glomerular filtration pressure. Hyperfiltration injury leads to microalbuminuria which eventually progresses to nephrotic syndrome
Nephrotic syndrome due to diabetes mellitus is characterized by sclerosis of the ______ and formation of __________ nodules
__________ may be used to slow the progression of hyperfiltration-induced damage
Mesangium; Kimmelstiel-Wilson
ACE inhibitors
What is the most commonly involved organ in systemic amyloidosis?
Kidney
How does systemic amyloidosis affect the kidney?
Amyloid deposits in mesangium resulting in nephrotic syndrome
Characterized by apple-green birefringence under polarized light
Nephritic syndrome is characterized by glomerular inflammation and bleeding. What are the other features?
Limited proteinuria (<3.5 g/day)
Oliguria and azotemia
Salt retention with periorbital edema and HTN
RBC casts and dymorphic RBCs in urine
What would biopsy show in nephritic syndrome?
Hypercellular, inflamed glomeruli
[Immune-complex deposition activates complement. C5a attracts neutrophils, which mediate damage]
PSGN is a nephritic syndrome that arises after group A beta-hemolytic strep infection of skin (impetigo) or pharynx. In particular, it occurs with nephritogenic strains. These strains carry what virulence factor?
M protein
Clinical features of PSGN
Nephritic syndrome arising 2-3 weeks after strep infection; usually seen in children, but may occur in adults
Hematuria (cola-colored urine), oliguria, HTN, periorbital edema
PSGN findings on H and E, EM, and IF
H and E = hypercellular, inflamed glomeruli
EM = subepithelial “humps”
IF = granular
PSGN treatment is supportive; children rarely progress to renal failure. However, some adults develop ______
RPGN
RPGN is a nephritic syndrome that progresses to renal failure in weeks to months. What is the hallmark biopsy finding on H and E?
Crescents in Bowman space
[comprised of fibrin and macrophages]
Once RPGN is diagnosed, the clinical picture and IF help to determine the etiology.
What is the etiology associated with linear IF pattern?
Goodpasture syndrome
[Antibody against collagen in glomerular and alveolar basement membranes; presents as hematuria and hemoptysis, classically in young adult males]
Once RPGN is diagnosed, the clinical picture and IF help to determine the etiology.
What 2 etiologies are associated with granular IF pattern?
PSGN or diffuse proliferative glomerulonephritis
Renal pathology caused by diffuse antigen-antibody complex deposition, usually sub-endothelial; most common type of renal disease in SLE
Diffuse proliferative glomerulonephritis
Once RPGN is diagnosed, the clinical picture and IF help to determine the etiology.
What 3 etiologies are associated with a negative IF (pauci-immune)?
Wegener granulomatosis (c-ANCA)
Microscopic polyangiitis (p-ANCA)
Churg-Strauss syndrome (p-ANCA)
Renal pathology due to antibody against collagen in glomerular and alveolar basement membranes; presents as hematuria and hemoptysis, classically in young adult males
Goodpasture syndrome
Wegener granulomatosis presents with hematuria and hemoptysis, very similarly to Goodpasture syndrome. However, what is the clinical feature that makes Wegener granulomatosis the more likely diagnosis?
Nasopharyngeal symptoms
[i.e., hx of recurrent sinusitis]
Microscopic polyangiitis and Churg-Strauss are both associated with p-ANCA. What are the 3 features that distinguish Churg-Strauss from microscopic polyangiitis?
Granulomatous inflammation
Eosinophilia
Asthma
Most common cause of nephropathy worldwide
IgA nephropathy
Clinical features of IgA nephropathy
Episodic gross or microscopic hematuria with RBC casts, usually following mucosal infections
May slowly progress to renal failure
Inherited defect in type IV collagen (most commony X-linked) resulting in thinning and splitting of glomerular basement membrane. Presents with isolated hematuria, sensory hearing loss, and ocular disturbances
Alport syndrome
T/F: Systemic signs are usually absent with cystitis
True
Urinalysis, dipstick, and culture results associated with cystitis
Urinalysis = cloudy with >10 WBCs/hpf
Dipstick = positive leukocyte esterase (d/t pyuria) and nitrites
Culture = >100,000 CFUs
5 major causes of cystitis
E.coli (80% of cases)
Staphylococcus saprophyticus
Klebsiella pneumoniae
Proteus mirabilis
Enterococcus faecalis
Alkaline urine with an ammonia scent may indicate what etiology for cystitis?
Proteus mirabilis
Pyuria with negative urine culture (sterile pyuria) may indicate what?
Urethritis due to Chlamydia trachomatis or Neisseria gonorrhoeae
Pyelonephritis presents with fever, flank pain, ______ casts, and leukocytosis in addition to symptoms of cystitis
WBC
3 most common pathogens for pyelonephritis
E coli (90%)
Klebsiella species
Enterococcus faecalis
Multiple bouts of acute pyelonephritis may lead to chronic pyelonephritis, characterized by insterstitial _______, and _______ of tubules. It is often due to ____________ (children), or ________
Fibrosis; atrophy
Vesicoureteral reflux; obstruction
What are the hallmark features of chronic pyelonephritis on gross examination? What features indicate vesicoureteral reflux as the cause?
Cortical scarring with blunted calyces
Vesicoureteral reflux is indicated by scarring at upper and lower poles
Histological features of chronic pyelonephritis and what type of casts are seen
“Thyroidization” of the kidney — atrophic tubules contain eosinophilic proteinaceous material reminiscent of thyroid follicles
Waxy casts may be seen in urine
Most common type of kidney stone; usually seen in adults
Calcium oxalate and/or calcium phosphate
Second most common type of kidney stone; most commonly due to infection with urease-positive organisms (e.g., Proteus vulgaris or Klebsiella); alkaline urine leads to stone formation
Ammonium magnesium phosphate (Staghorn calculi)
Third most common stone (5% of cases); radiolucent (as opposed to other types of stones which are radioopaque)
Uric acid
Rare cause of nephrolithiasis; most commonly seen in children
Cysteine
[associated with cystinuria — a genetic defect of tubules that results in decreased reabsorption of cysteine; these may also form staghorn calculi. Treatment involves hydration and alkalinization of urine]
What type of kidney stone is associated with Crohn disease?
Calcium oxalate and/or calcium phosphate
Treatment for recurrent calcium oxalate and/or calcium phosphate renal stones
Hydrochlorothiazide (calcium-sparing diuretic)
Most common cause of calcium oxalate or calcium phosphate renal stones
Idiopathic hypercalciuria
Why must staghorn calculi be surgically removed?
They may act as a nidus for UTI
End-stage kidney failure may result from glomerular, tubular, inflammatory, or vascular insults. What are the 3 most common causes of end-stage kidney failure?
Diabetes mellitus
HTN
Glomerular disease
One clinical feature of ESRF is uremia, characterized by increased nitrogenous waste products in the blood (azotemia). What are the associated clinical features?
Nausea, anorexia, pericarditis, platelet dysfunction, encephalopathy with asterixis, and deposition of urea crystals in skin
Where (specifically) is EPO made?
Renal peritubular interstitial cells
Clinical features of ESRF
Uremia
Salt and water retention with resultant HTN
Hyperkalemia with HAGMA
Anemia
Hypocalcemia
Renal osteodystrophy (osteitis fibrosa cystica, osteomalacia, and osteoporosis)
Treatment for ESRF involves dialysis or renal transplant. _____ often develop within shrunken end-stage kidneys during dialysis. There is also increased risk for _____________
Cysts; renal cell carcinoma
Renal hamartoma comprised of blood vessles, smooth muscle, and adipose tissue
Angiomyolipoma
Angiomyolipomas are seen with increased frequency in what condition/
Tuberous sclerosis
RCC is a malignant epithelial tumor arising from kidney tubules. What is the classic triad of presenting symptoms?
Hematuria
Palpable mass
Flank pain
[Note that fever, weight loss, or paraneoplastic syndrome (e.g., EPO, renin, PTHrP, or ACTH) may be present. Also note that classic triad is only seen all together in 10% of pts]
Rarely, RCC may present with ____-sided varicocele
Left
Gross and microscopic findings of RCC
Gross exam reveals yellow mass
Microscopically, most common variant exhibits clear cytoplasm (clear cell type)
Pathogenesis of RCC involves loss of ___________ gene on chromosome
VHL (tumor suppressor); 3p
Pathogenesis of RCC involves loss of VHL (3p) tumor suppressor gene. This leads to increased _____ which promotes growth, and increased _____ transcription factor which then increases VEGF and PDGF
IGF-1; HIF
RCC may be hereditary or sporadic. What is the difference in presentation between these 2 types?
Hereditary — Multiple tumors in younger pt, often bilateral
Sporadic — Single tumor in upper pole of kidney in adult smoker
Von Hippel-Lindau Disease is an ______ ________ inherited disorder associated with inactivation of the VHL gene.
This leads to increased risk for what 2 malignancies?
Autosomal dominant
Hemangioblastoma of the cerebellum; Renal cell carcinoma
How is renal cell carcinoma staged?
T — based on tumor size and involvement of renal vein
N — based on spread to retroperitoneal LNs
Malignant kidney tumor comprised of blastema, primitive glomeruli and tubules, and stromal cells; most common malignant renal tumor in children with average age of 3 years
Wilms tumor
[Presents as large, unilateral flank mass with hematuria and HTN (due to renin secretion)]
Wilms tumor is associated with ____ mutation, especially in syndromic cases
WT1
WT1 mutations are seen in WAGR syndrome — what are the clinical features?
Wilms tumor
Aniridia
Genital abnormalities
Mental and motor Retardation
Syndrome that includes wilms tumor, neonatal hypoglycemia, muscular hemihypertrophy, and organomegaly (e.g., tongue)
Beckwith-Wiedemann Syndrome
Most common type of lower urinary tract cancer; usually arises in the bladder
Urothelial carcinoma
[Malignant tumor arising from urothelial lining of renal pelvis, ureter, bladder, or urethra]
Major risk factors for urothelial carcinoma
Cigarette smoke (polycyclic aromatic hydrocarbons)
Naphthylamine (component of cigarette smoke)
Azo dyes
Long-term cyclophosphamide or phenacetin
Urothelial carcinoma is generally seen in older adults and classically presents with _____ ____
Painless hematuria
Urothelial carcinoma arises via 2 distinct pathways - what are they, and which one is associated with early p53 mutations?
Flat — starts as high grade, progresses to invade; associated with early p53 mutations
Papillary — tumors start low grade, progress to high grade, then eventually invade
Urothelial carcinoma tumors are often multifocal and recur. This is because the entire mucosa is affected in a phenomenon known as the _____ ______
Field defect
Another cancer that may occur in the lower urinary tract is squamous cell carcinoma, which is a malignant proliferation of squamous cells, usually involving the bladder. It arises in a background of squamous metaplasia. What are the 3 key risk factors for squamous cell carcinoma of the lower urinary tract?
Chronic cystitis
Schistosoma hematobium
Long-standing nephrolithiasis
Adenocarcinoma may also occur in the lower urinary tract; this is a malignant proliferation of glands that usually involves the bladder. There normally is not glandular epithelium lining the bladder, so this type of cancer only arises in particular circumstances. What are 3 circumstances associated with development of adenocarcinoma in the lower urinary tract?
Urachal remnant — failure of this structure to involute; adenocarcinoma in this case will be present at dome of the bladder
Cystitis glandularis — chronic inflammation of bladder leading to columnar metaplasia
Exstrophy — congenital failure to form the caudal portion of the anterior abdominal and bladder walls
