Quiz 2 Flashcards
(42 cards)
Nephrotic Syndrome
proteinuria (>3.5 g/day)
injury to podocytes
change in glomerual architecture - scarring
podocyte disruption → charge barrier impaired. Massive proteinuria (> 3.5 g/day) with hypoalbuminemia, hyperlipidemia, edema. May be 1° (eg, direct podocyte damage) or 2° (podocyte damage from systemic process [eg, diabetes]).
- Focal segmental glomerulosclerosis (1° or 2°)
- Minimal change disease (1° or 2°)
- Membranous nephropathy (1° or 2°)
- Amyloidosis (2°)
- Diabetic glomerulonephropathy (2°)
Nephritic syndrome
hematuria - also dysmorphic RBCs and RBC casts
inflammation and prolifferation of immune cells
breaks in GBM
some protein, but <3.5g/day
high BP
decreased GFR
due to GBM disruption. Hypertension, ↑ BUN and creatinine, oliguria, hematuria, RBC casts in urine. Proteinuria often in the subnephrotic range (< 3.5 g/day) but in severe cases may be in nephrotic range.
- Acute poststreptococcal glomerulonephritis
- Rapidly progressive glomerulonephritis
- IgA nephropathy (Berger disease)
- Alport syndrome
- Membranoproliferative glomerulonephritis
Fanconi Syndrome
Generalized reabsorption defect in PCT –> INCREASEDexcretion of amino acids, glucose, HCO3–, and PO43–, and all substances reabsorbed by the PCT
Effects:May lead to metabolic acidosis (proximal RTA), hypophosphatemia, osteopenia
Causes: Hereditary defects (eg, Wilson disease, tyrosinemia, glycogen storage disease), ischemia, multiple myeloma, nephrotoxins/drugs (eg, ifosfamide, cisplatin, expired tetracyclines), lead poisoning
Barter Syndrome
Resorptive defect in thick ascending loop of Henle (affects Na+/K+/2Cl– cotransporter)
Effects:Metabolic alkalosis, hypokalemia, hypercalciuria
Causes: Autosomal recessive Presents similarly to chronic loop diuretic use
Liddle Syndrome
Gain of function mutation –> INCREASEDactivity of Na+ channel –> INCREASED Na+ reabsorption in collecting tubules
Effects: Metabolic alkalosis, hypokalemia, hypertension, DECREASEDaldosterone
Causes: Autosomal dominant Presents similarly to hyperaldosteronism, but aldosterone is nearly undetectable Treat with amiloride
Syndrome of Apparent Mineralcoricoid Excess
In cells containing mineralocorticoid receptors, 11β-hydroxysteroid dehydrogenase converts cortisol (can activate these receptors) to cortisone (inactive on these receptors) Hereditary deficiency of 11β-hydroxysteroid dehydrogenase –> excess cortisol –> INCREASEDmineralo corticoid receptor activity
Effects: Metabolic alkalosis, hypokalemia, hypertension DECREASEDserum aldosterone level; cortisol tries to be the SAME as aldosterone
Causes: Autosomal recessive Can acquire disorder from glycyrrhetinic acid (present in licorice), which blocks activity of 11β-hydroxysteroid dehydrogenase
Treat with K+-sparing diuretics (DECREASEDmineralocorticoid effects) or corticosteroids (exogenous corticosteroid–> endogenous cortisol production —> DECREASEDmineralocorticoid receptor activation
Potassium Shifts into cell
hypoosmolality
insulin
alkalosis
beta agonist
Potassium shifts out of cell
hyperosmolarity high blood sugar (low insulin) beta blockers digitalis (blocks ATPase) acidosis cell injury - lysis
metabolic acidosis
elevated anion gap:
Methanol (formic acid) Uremia Diabetic ketoacidosis Propylene glycol Iron tablets or INH Lactic acidosis Ethylene glycol (oxalic acid) Salicylates (late)
normal anion gap:
Hyperalimentation Addison disease Renal tubular acidosis Diarrhea Acetazolamide Spironolactone Saline infusion
Renal Tubular Acidosis Type 1
Distal
Inability of α-intercalated cells to secrete H+ –> no new HCO3– is generated –> metabolic acidosis
urine pH> 5.5
decreased serum K
Causes: Amphotericin B toxicity, analgesic nephropathy, congenital anomalies (obstruction) of urinary tract, autoimmune diseases (eg, SLE)
INCREASEDrisk for calcium phosphate kidney stones (due to INCREASEDurine pH and INCREASEDbone turnover)
Renal Tubular Acidosis Type 2
Proximal
Defect in PCT HCO3– reabsorption –> INCREASEDexcretion of HCO3– in urine –> metabolic acidosis Urine can be acidified by α-intercalated cells in collecting duct, but not enough to overcome the increased excretion of HCO3– –> metabolic acidosis
urine pH< 5.5
decreased serum K
Causes: Fanconi syndrome, multiple myeloma, carbonic anhydrase inhibitors
ICREASEDrisk for hypophosphatemic rickets (in Fanconi syndrome)
Renal Tubular Acidosis Type 4
Hyperkalemic
Hypoaldosteronism or aldosterone resistance; hyperkalemia –> DECREASED NH3 synthesis in PCT –> DECREASEDNH4+ excretion
urine pH< 5.5 (or variable)
High Serum K
causes: DECREASEDaldosterone production (eg, diabetic hyporeninism, ACE inhibitors, ARBs, NSAIDs, heparin, cyclosporine, adrenal insufficiency) or aldosterone resistance (eg, K+-sparing diuretics, nephropathy due to obstruction, TMP-SMX)
minimal change disease
Nephrotic
Most common cause of nephrotic syndrome in children. Often 1° (idiopathic) and may be triggered by recent infection, immunization, immune stimulus. Rarely, may be 2° to lymphoma (eg, cytokine-mediated damage). 1° disease has excellent response to corticosteroids.
LM—Normal glomeruli (lipid may be seen in PCT cells) IF—⊝
EM—effacement of podocyte foot processes
Focal segmental glomerulosclerosis
Nephrotic
Most common cause of nephrotic syndrome in African-Americans and Hispanics. Can be 1° (idiopathic) or 2° to other conditions (eg, HIV infection, sickle cell disease, heroin abuse, massive obesity, interferon treatment, or congenital malformations). 1° disease has inconsistent response to steroids. May progress to CKD. LM—segmental sclerosis and hyalinosis B IF—often ⊝ but may be ⊕ for nonspecific focal deposits of IgM, C3, C1 EM—effacement of foot processes similar to minimal change disease
Membranous Nephropathy
Nephrotic
Also known as membranous glomerulonephritis. Can be 1° (eg, antibodies to phospholipase A2 receptor) or 2° to drugs (eg, NSAIDs, penicillamine, gold), infections (eg, HBV, HCV, syphilis), SLE, or solid tumors. 1° disease has poor response to steroids. May progress to CKD. LM—diffuse capillary and GBM thickening C IF—granular due to IC deposition EM—“Spike and dome” appearance of subepithelial deposits
Amyloidosis
Nephrotic
Kidney is the most commonly involved organ (systemic amyloidosis). Associated with chronic conditions that predispose to amyloid deposition (eg, AL amyloid, AA amyloid). LM—Congo red stain shows apple-green birefringence under polarized light due to amyloid deposition in the mesangium
diabetic glomerulonephropathy
Nephrotic
Most common cause of ESRD in the United States. Hyperglycemia –>nonenzymatic glycation of tissue proteins –> mesangial expansion; GBM thickening and INCREASEDpermeability. Hyperfiltration (glomerular HTN and INCREASEDGFR) –>glomerular hypertrophy and glomerular scarring (glomerulosclerosis) leading to further progression of nephropathy.
LM—Mesangial expansion, GBM thickening, eosinophilic nodular glomerulosclerosis (Kimmelstiel-Wilson lesions, arrows in D)
Acute poststreptococcal glomerulonephritis
nephritic
Most frequently seen in children. ~ 2–4 weeks after group A streptococcal infection of pharynx or skin. Resolves spontaneously in most children; may progress to renal insufficiency in adults. Type III hypersensitivity reaction. Presents with peripheral and periorbital edema, cola-colored urine, HTN. ⊕ strep titers/serologies, DECREASEDcomplement levels (C3) due to consumption. LM—glomeruli enlarged and hypercellular A IF—(“starry sky”) granular appearance (“lumpy-bumpy”) B due to IgG, IgM, and C3 deposition along GBM and mesangium EM—subepithelial immune complex (IC) humps
Rapidly progressive (crescentic) glomerulonephritis
Nephritic
Poor prognosis, rapidly deteriorating renal function (days to weeks). LM—crescent moon shape C. Crescents consist of fibrin and plasma proteins (eg, C3b) with glomerular parietal cells, monocytes, macrophages Several disease processes may result in this pattern which may be delineated via IF pattern.
Linear IF due to antibodies to GBM and alveolar basement membrane: Goodpasture syndrome—hematuria/hemoptysis; type II hypersensitivity reaction; Treatment: plasmapheresis
Negative IF/Pauci-immune (no Ig/C3 deposition): Granulomatosis with polyangiitis (Wegener)—PR3-ANCA/c-ANCA or Microscopic polyangiitis—MPO-ANCA/p-ANCA
Granular IF—PSGN or DPGN
Diffuse proliferative glomerulonephritis
Nephritic
Often due to SLE (think “wire lupus”). DPGN and MPGN often present as nephrotic syndrome and nephritic syndrome concurrently.
LM—“wire looping” of capillaries
IF—granular; EM—subendothelial and sometimes intramembranous IgG-based ICs often with C3 deposition
IgA nephropathy (Berger disease)
Nephritic
Episodic hematuria that occurs concurrently with respiratory or GI tract infections (IgA is secreted by mucosal linings). Renal pathology of IgA vasculitis (HSP). LM—mesangial proliferation
IF—IgA-based IC deposits in mesangium; EM—mesangial IC deposition
Alport Syndrome
Nephritic
Mutation in type IV collagen –> thinning and splitting of glomerular basement membrane. Most commonly X-linked dominant. Eye problems (eg, retinopathy, lens dislocation), glomerulonephritis, sensorineural deafness; “can’t see, can’t pee, can’t hear a bee.” EM—“Basket-weave”
Membranoproliferative glomerulonephritis
nephritic
MPGN is a nephritic syndrome that often co-presents with nephrotic syndrome. Type I may be 2° to hepatitis B or C infection. May also be idiopathic. Subendothelial IC deposits with granular IF Type II is associated with C3 nephritic factor (IgG antibody that stabilizes C3 convertase persistent complement activation –> DECRESEDC3 levels). Intramembranous deposits, also called dense deposit disease In both types, mesangial ingrowth GBM splitting “tram-track” appearance on H&E D and PAS E stains.
Kidney Stones - Calcium
Calcium oxalate: hypocitraturia
Radiopaque
Shaped like envelope A or dumbbell
Calcium stones most common (80%); calcium oxalate more common than calcium phosphate stones. Hypocitraturia often associated with LOW urine pH.
Can result from ethylene glycol (antifreeze) ingestion, vitamin C abuse, hypocitraturia, malabsorption (eg, Crohn disease).
Treatment: thiazides, citrate, low-sodium diet.
Calcium phosphate: HIGHpH
Radiopaque
Wedgeshaped prism
Treatment: low-sodium diet, thiazides.
