Renal pathology Flashcards
Hartnup disease
Autosomal recessive deficiency of neutral amino acid (e.g. tryptophan) transporters in proximal renal tubular cells and enterocytes, which leads to neutral aminoaciduria and decreased absorption from the gut
Pellagra-like symptoms
Tx: high-protein diet and nicotinic acid
Fanconi syndrome
Reabsorptive defect in the PCT, leading to increased excretion of amino acids, glucose, phosphate, and bicarb (type II RTA).
Causes: Wilson disease, ischemia, nephrotoxins/drugs
Order of renal tubular defects: Fanconi, Bartter, Gitelman, Liddle (“the kidneys put out FABulous Gliterring Liquid”)
Bartter syndrome
Autosomal recessive reabsorptive defect in thick ascending loop of Henle. Affects Na/K/2Cl cotransporter (effects similar to loop diuretics)
Results in hypokalemia and metabolic alkalosis with hypercalciuria
Gitelman syndrome
Autosomal recessive reabsorptive defect of NaCl in DCT. Affects similar to thiazide diuretics.
Hypokalemia and metabolic alkalosis without hypercalciuria.
Less severe than Bartter syndrome
Liddle syndrome
Autosomal dominant, increased activity of epithelial Na+ channels in distal and collecting tubules.
HTN, hypokalemia, metabolic alkalosis, decreased aldosterone.
Tx: amiloride
Polycystic kidney disease (PKD)
Inherited defect leading to bilateral enlarged kidneys with cysts in the renal cortex and medulla
Autosomal recessive form - presents in infants; cysts in kidney and liver; portal HTN (due to hepatic fibrosis)
Autosomal dominant form - presents in young adults; mutation in APKD1/2; cysts in kidney, liver, and brain (berry aneurysms); mitral valve prolapse
Acute tubular necrosis
Most common cause of intrarenal azotemia; presents with brown granular casts and hyperkalemia
Etiology may be ischemic or nephrotoxic
- Proximal tubule and medullary segment of thick ascending limb are most susceptible to ischemic damage
- Proximal tubule is most susceptible to nephrotoxins
Nephrotoxins
Nephrotoxins cause acute tubular necrosis.
- Aminoglycosides (e.g. gentamicin)
- Heavy metals (e.g. lead)
- Myoglobinuria
- Ethylene glycol (oxalate crystals in urine)
- Radiocontrast dye
- Urate (tumor lysis syndrome; PPx with hydration and allopurinol)
Acute interstitial nephritis
Drug-induced hypersensitivity involving interstitium and tubules; characterized by oliguria, fever, and eosinophils in urine
Causes: NSAIDs, penicillin, diuretics
May progress to renal papillary necrosis
Renal papillary necrosis
Presents with gross hematuria and flank pain
Causes:
- Chronic analgesic abuse (penacetin/aspirin use)
- Diabetes
- Sickle cell
- Severe acute pyelonephritis
Nephrotic syndrome
Glomerular disorders characterized by proteinuria (> 3.5 g/day) resulting in:
- Hypoalbuminemia (pitting edema)
- Hypogammaglobulinemia (increased risk of infection)
- Hypercoagulable state (loss of antithrombin III)
- HLD and hypercholesterolemia (fatty casts in urine)
Minimal change disease
Nephrotic syndrome; most common in children.
May be associated with Hodgkin lyphoma (cytokine release disrupts podocytes)
Effacement of foot processes results in loss of albumin but not immunoglobulin
Excellent response to steroids (unique among nephrotic syndromes)
Focal segmental glomerulosclerosis (FSGS)
Nephrotic syndrome
Hispanics and African Americans
HIV, heroin use, sickle cell disease
Like MCD, FSGS involves effacement of the foot process
Unlike MCD, FSGS does NOT respond well to steroids. Progresses to chronic renal failure
Membranous nephropathy
Nephrotic syndrome
Caucasian adults
Hepatitis B or C, solid tumors, SLE, drugs (e.g. NSAIDs, penicillamine)
Immune complexes deposit below the podocytes (subepithelial deposits) to produce granular IF and “spike and dome” appearance on EM
Progresses to chronic renal failure
Membranoproliferative glomerulonephritis (MPGN)
Mixed nephrotic/nephritic syndrome
“Tram-track” appearance on H&E and granular IF
- Type I MPGN - subendothial immune complex deposits; associated with HBV and HCV
- Type II MPGN - intramembranous immune complex deposits; associated with C3 nephritic factor (leads to overactivation of complement and inflammation)
Progresses to chronic renal failure
Effect of diabetes on the kidneys
- Nonenzymatic glycosylation of vascular basement membrane
- Hyaline arteriosclerosis (especially glomerular efferent arteriole)
- Hyperfiltration injury leads to nephrotic syndrome (sclerosis of mesangium with Kimmelstiel-Wilson nodules)
PPx: ACE inhibitors
Effect of systemic amyloidosis on the kidneys
Amyloid deposits in mesangium, resulting in nephrotic syndrome
Post-streptococcal glomerulonephritis (PSGN)
Nephritic syndrome
Presents 2-3 weeks after infection with nephritogenic strain of GAS (M protein virulence factor)
Immune complex deposition (granular IF) due to IgG, IgM, and C3 deposition; subepithelial “humps” on EM
Increased anti-DNase B. Decreased complement.
Usually resolves, but 25% of adults progress to rapidly progressive glomerulonephritis
Rapidly progressive glomerulonephritis (RPGN)
Nephritic syndrome
Progresses to renal failure in weeks to months
Crescents in Bowmn space (comprised of fibrin, C3b, and macrophages)
Etiology of RPGN determined by IF pattern:
- Linear (anti-basement membrane antibody) - Goodpasture syndrome
- Granular (immune complex deposition) - PSGN or diffuse proliferative glomerulonephritis
- Negative IF (pauci-immune) - Wegener granulomatosis (c-ANCA), microscopic polyangitis (p-ANCA); Churg-Strauss (p-ANCA and granulomas/asthma/eosinophilia)
IgA nephropathy
Nephritic syndrome
Usually follows mucosal infection (e.g. gastroenteritis)
IgA deposits in mesangium
Alport syndrome
Nephritic syndrome
X-linked defect of type IV collagen
Isolated hematuria, sensory hearing loss, ocular disturbances
Calcium oxalate/calcium phosphate nephrolithiasis
Most common type of nephrolithiasis.
Envelope/dumbbell shaped crystals
Idiopathic hypercalciuria, hypercalcemia.
Ethylene glycol (antifreeze), vitamin C abuse, and Crohn disease promote formation of oxalate crystals.
Calcium phosphate crystals precipitate at alkalinic pH. Calcium oxalate crystals precipitate at acidic pH
Tx: HCTZ (Ca-sparing diuretic), citrate
Ammonium magnesum phosphate (struvite) nephrolithiasis
Coffin lid-shaped crystals
Infection with urease-positive organisms (e.g. Proteus, Staph or Klebsiella) that hydrolyze urea to ammonia
Staghorn calculi (nidus for UTIs) precipitate at alkalinic pH
Tx: Surgical removal of staghorn calculi, eradication of pathogen
Uric acid nephrolithiasis
Radiolucent (unique among stones); rhomboid-shaped crystals
Hyperuricemia (leukema, myeloproliferative disorders, gout)
Risk factors include low urine volumes and acidic pH
Tx: hydration, alkalinization of the urine (potassium bicarbonate), allopurinol
Cystine nephrolithiasis
Hexagonal shaped crystals
Children; associated with decreased reabsorption of cysteine
Staghorn calculi (like ammonium magnesium phosphate stones)
Tx: hydration and alkalnization of urine
Chronic renal failure
- Uremia (nausea, anorexia, pericarditis, platelet dysfunction, encephalopathy with asterixis, deposition of urea crystals in skin)
- HTN
- Hyperkalemia with metabolic acidosis
- Anemia (decreased EPO production by renal peritubular interstitial cells)
- Hypocalcemia and hyperphosphatemia (decreased 1-alpha-hydroxylation by proximal renal tubule cells)
- Renal osteodystrophy due to secondary hyperparathyroidism, osteomalacia (decreased mineralization), and osteoporosis (metabolic acidosis)
- Dyslipidemia (hypertriglyceridemia)
- Waxy casts
Increases risk for RCC
Renal cell carcinoma
Hematuria, palpable mass, flank pain
Paraneoplastic syndromes: EPO, renin, PTHrP, ACTH
Left-sided varcocele due to involvement of left renal vein
Loss of VHL (3p) tumor suppressor gene
Sporadic tumors - single tumor in upper pole of kidney; adult male smokers
Hereditary tumors - bilateral tumors, young adults.
Von Hippel-Lindau disease
Autosomal dominant disorder associated with inactivation of VHL gene
Hemangioblastoma of the cerbellum and bilateral renal cell carcinomas
WAGR syndrome
WAGR: Wilms tumor, Aniridia, Genital abnormalities, mental and motor Retardation
Deletion of WT1 tumor suppressor gene (11p13)
Denys-Drash syndrome
Wilms tumor, progressive glomerular disease, male pseudohermaphroditism
Mutation of WT1 tumor suppressor gene (11p13)
Beckwith-Wiedemann syndrome
Wilms tumor, neonatal hypoglycemia, muscular hemihypertrophy, organomegaly (including tongue)
Mutations in WT2 gene cluster
Urothelial (transitional cell carcinoma)
Arises from urothelial lining of renal pelvis, ureter, bladder, or urethra
Risk factors: cigarette smoke, naphtylamine, azo dyes, long-term cyclophosphamide or phenacetin use
Painless hematuria
Two pathways: flat (high-grade, early p53 mutation), papillary (low-grade, late p53 mutation)
Tumors are often multifocal and recur (“field defect”)
Squamous cells carcinoma of the bladder
Risk factors:
- Chronic cystitis (older woman)
- Schistosoma hematobium infection (young Egyptian male)
- Long-standing nephrolithiasis
Adenocarcinoma of the bladder
Etiologies:
- Urachal remnant (tumor develops at dome of bladder)
- Cystitis glandularis (chronic inflammation of bladder)
- Exstrophy (congenital failure to form caudal portion of anterior abdominal and bladder walls)
Diffuse proliferative glomerulonephritis
Nephritic syndrome. Etiology of rapidly progressive glomerulonephritis
Sub-endothelial deposits of IgG and C3
“Wire-looping” of capillaries
Most common caused of death in SLE
Metabolic alkalosis with low urine Cl-
Often associated with volume depletion (increased reabsorption of bicarb in the proximal tubule)
Responds to saline infusion (repletes Cl- and volume)
Etiologies: vomiting, contraction alkalosis, previous thiazide use, cystic fibrosis
Metabolic alkalosis with high urine Cl-
Often associated with volume expansion and hypokalemia
Resistant to saline infusion therapy
Etiologies: hyperaldosteronism, severe hypokalemia, current diuretic therapy, Bartter’s syndrome or Gittelman syndrome, aminoglycoside toxicity
