Renal Pathology Flashcards by Sarah Gillen

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

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Unilateral renal agenesis leads to _______ of existing kidney. _______ increases the risk of renal failure later in life

Hypertrophy; hyperfiltration

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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)

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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!]

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T/F: dysplastic kidney is most commonly unilateral

True

NOTE — when it is bilateral, it must be distinguished from inherited polycystic kidney disease

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Inherited renal defect resulting in bilateral enlarged kidneys with cysts in renal cortex and medulla

Polycystic kidney disease

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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

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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

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3 associations with autosomal dominant PKD

Berry aneurysm
Hepatic cysts
Mitral valve prolapse

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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

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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

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Cause of prerenal azotemia

Decreased blood flow to kidneys

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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)

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What causes postrenal azotemia?

Obstruction of urinary tract downstream from kidney

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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

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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!

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Most common cause of acute renal failure

Acute tubular necrosis — causes injury and necrosis of tubular epithelial cells

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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

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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

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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)

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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)

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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]

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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)

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Drug-induced HSR of interstitium and tubules, resulting in intrarenal acute renal failure

Acute interstitial nephritis

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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