R13 Edema and diuretics

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  1. Principles of edema
    • -Effective circulating volume reflects volume of blood perfusing vital organs
    • -ECV ≃EABV (effective arterial blood volume)
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    • *Fluid accumulation is a result of: 
    • 1. Sustained increase net pressure gradient
    • 2. reduced lymph flow
  2. Response to ↓ ECV
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  3. Normal movement of fluid
    • Starling equation; governed by hydrostatic and oncotic pressures
    • High arterial pressure drives fluid into the interstitium
    • Lymphatics drain fluid back to circulation
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  4. ↓ CO → ↓ ECV → volume expansion
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  5. ↓ Arterial compliance → ↓ ECV
    • "arterial under-filling"
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  6. Consequences of arterial underfilling
    • Ventricular/arterial receptors→
    • 1. Stimulation of SNS
    • 2. Activation of RAAS
    • 3. Non-osmotic vasopressin stimulation

    → Increased systemic and renal arterial vascular resistance
  7. How do we correct the cycle?
    • Diuretics: block some of the system
    • limit reabsorption of sodium
  8. Proximal tubule
    Na handling, diuretic
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    • Carbonic Anhydrase inhibitors
  9. Loop of Henle
    Na handling, diuretics
    • Majority of Na reabsorption is handled by loop of henle
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    • NKCC2: loop diuretics
  10. Collecting duct
    Na handling, Aldosterone
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  11. Collecting duct
    Principal cells, intercalated cells
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  12. Diuretics
    location of action
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  13. Considerations for diuretics
    bioavailability, elimination half-life
    Bioavailability, elimination half-life

    • Loop diuretics: furosemide, bumetanide, torsemide
    • -bioavailability ~90%
    • -t1/2 (1-2hr, 1hr, 4-6hr, respectively)

    • Thiazides: HCTZ, Chlorthalidone
    • -bioavailability 60-80%
    • -t1/2 (HCTZ is 2-4hrs, chlorthalidone 24-48hrs)
    • -Thiazides produce more hypokalemia than loop diuretics (longer half-life)

    • Potassium-sparing diureticsAmiloride, triamterene, spironolactone, eplerenone
    • -bioavalibility ~80%
    • -t1/2 (amiloride ~24hrs, all others ~2hrs)
    • -K-sparing only helpful if pt has primary or secondary hyperaldosteronism

    • CA inhibitors...
    • -aren't used often:
    • -increased Na delivery to loop of henle increases reabsorption
  14. Diuretics
    effect on Na+ balance
    • Net negative salt balance after diuretics:
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  15. Diuretics
    effect on cardiac and renal function
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  16. Diuretic resistance/response
    loop diuretic holiday
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    • Plasma concentration vary with disease state:
    • -Compensated CHF will have increased plasma concentration earlier than decompensated
  17. Combination therapy
    • Loop diuretics (or other) are often used in combination with mineralocorticoids:
    • -aim is to block compensatory effect of the RAAS
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  18. Combination diuretic therapy
    benefits and AEs
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  19. loop diuretics
    clinical conditions with diminished response
    • Renal insufficiency: impaired delivery to the site of action
    • -Solution: increase frequency of effective dose

    • Nephrotic syndrome: diminished nephron response: binding of diuretic to urinary protein
    • -Solution: increase frequency of effective dose

    • Cirrhosis: diminished nephron response
    • -Solution: increase frequency of effective dose

    • Heart failure: diminished nephron response
    • -Solution: increase frequency of effective dose
  20. Treatment failure
    • Noncompliance
    • -drug regimen
    • -Na restriction

    • True diuretic resistance
    • -altered intestinal absorption
    • -Decreased renal perfusion caused by low volume, arterial disease, drug use (NSAIDs, ACE-In)
    • -Reduced tubular secretions caused by low volume, kidney disease, drug use
    • -Tolerance
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Card Set:
R13 Edema and diuretics
2013-03-10 00:45:45
Renal II

Edema and diuretics
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