To Pee or not to Pee?: The Edema Dilemma
Q: How do cardiac, renal and hepatic edema differ with respect to diuretics given and why?
Looks like Urine trouble. Guess what…We've got your back.
Let's start by breaking down the pathophysiology of edema in these conditions which would then help us understand the rationale of administering a diuretic.
A) Cardiac Edema:
The edema in heart failure is due to a :
A) Pump failure causing a mechanical backing up of fluid
B) Cardiovascular response to poor perfusion causing activation of the renin-angiotensin system (RAAS): Angiotensin II causes vasoconstriction of both afferent and efferent renal arterioles and stimulates release of aldosterone from the adrenal gland.
With this background in mind, we’ll come back to your specific question. Mild congestive heart failure is initially managed with a thiazide diuretic. However, loop diuretics (e.g., furosemide, torsemide, or bumetanide) are the principal drugs used in acute exacerbations.
Loop diuretics inhibit the reabsorption of sodium, chloride, and potassium in the thick ascending limb of Henle’s loop. They are more effective relievers of symptoms as compared to thiazides but do neither class of drugs affect the overall mortality of these patients.
Drugs like B Blockers like Carvedilol, ACE inhibitors like lisinopril and Mineralocorticoid Receptor Antagonists (MRAs) like Spironolactone are given to patients of CHF to reduce overall mortalitity and morbidity due to prolonged activation of RAAS.
B) Hepatic Edema
Patients with advanced liver cirrhosis show an abnormal regulation of extracellular fluid volume, resulting in the accumulation of fluid as ascites or edema. Cirrhosis is the most frequent cause of ascites.
The occurrence of ascites in cirrhosis is due to portal hypertension, which is responsible for:
a) Increase in hydrostatic pressure at the sinusoidal level and
b) The alterations of splanchnic and systemic haemodynamics: Increased splanchnic inflow, reduced systemic resistance and increased plasma volume and cardiac output.
c) Sodium Retention: Which occurs in the setting of increased RAA system and Sympathetic Nervous System activity.
The mechanisms by which portal hypertension leads to the activation of antinatriuretic factors and sodium retention are not completely understood; but there are theories that talk revolve around peripheral arterial vasodilatation.
Now,the million dollar question. What diuretic do we choose here?
Spironolactone is the first diuretic started in patients with cirrhosis, to which other diuretics may be added if response is inadequate.This drug causes a modest diuresis, which is typical of distally acting diuretics. Cirrhotic patients are often very sensitive to intravascular volume depletion. Spironolactone when used alone was as effective as its combined therapy with furosemide . However, this may cause gynecomastia. Amiloride can be used as an alternative, However it is not as effective as spironolactone.
But why, you ask? Well, it turns out, in comparing the efficacy of furosemide and spironolactone in a randomized comparative study, the activity of the renin angiotensin system proved to alter the action of these diuretics. Patients with high renin and aldosterone levels failed to respond to furosemide but were successfully treated with 300 mg per day of spironolactone.
In case of an inadequate response to spironolactone, thiazide diuretics are added to the regimen. Thiazides are terminated if the patient does not respond after 3 days and replaced with a loop diuretic.
Phew! Just hang in there for the last one alright? We’re almost there.
C) Renal Edema:
The leading causes of renal edema are nephrotic and nephritic syndromes. Edema is one of the cardinal clinical features of these syndromes, and may range from localized puffiness to massive anasarca.
The pathophysiological mechanisms of edema formation have been known to be primarily constituted of:
Thus, more than one single mechanism may be responsible for the renal salt retention observed in these diverse conditions.
We already know that the major proportion of filtered Na+ is reabsorbed in the proximal tubule (55%–60%) and in the loop of Henle (25%–30%); only 5%–7% of filtered sodium is reabsorbed in the distal segments of the renal tubular system.
However, in conditions causing renal edema, the efficacy of diuretics acting in proximal segments is hampered by compensatory increase of sodium and water by distal reabsorption in the ascending limb of Henle's loop. Therefore, loop diuretics, which can increase fractional excretion of Na+ up to 30%, remain the first choice for edema treatment in patients with these disorders.
However do keep in mind that due to low serum albumin levels, the diffusion of diuretics in the extracellular compartment is increased. Therefore, a combination of albumin and diuretic may be needed to achieve adequate levels of loop diuretic at the active site.
So keep these key concepts in mind and Urine the clear, mate!
By Dr Abhilasha Sharma
References:
1. Packer M, Cohn JN, Abraham WT. Consensus recommendations for the management of chronic heart failure. Am J Cardiol1999;83:1A–38.
2. Schrier MW, Abraham WT. Hormones and hemodynamics in heart failure. N Engl J Med1999;341:577–85.
3. Wilcox CS. Diuretics. In: Brenner BM, Rector FC, eds. The kidney. Philadelphia: WB Saunders, 1996: 2299–330.
4. Interrelationships between sodium clearance, plasma aldosterone, plasma renin activity, renal hemodynamics and blood pressure in renal disease Klin Wochenschr, 57 (1979), pp. 1273-1285
5. Epstein, M, Levinson, R, Sancho, J, Haber, E, and Re, R. Characterization of the renin-aldosterone system in decompensated cirrhosis. Circ Res. 1977; 41: 818–829
6. Bosch, J, Pizcuetá, P, Feu, F, Fernandez, M, and Garcia-Pagan, JC. Pathophysiology of portal hypertension. Gastroenterol Clin North Am. 1992 Mar; 21: 1–14
7. Sica DA, Gehr TW. Diuretic combinations in refractory oedema states: Pharmacokinetic-pharmacodynamic relationships. Clin Pharmacokinet 1996; 30:229-249.
Looks like Urine trouble. Guess what…We've got your back.
Let's start by breaking down the pathophysiology of edema in these conditions which would then help us understand the rationale of administering a diuretic.
A) Cardiac Edema:
The edema in heart failure is due to a :
A) Pump failure causing a mechanical backing up of fluid
B) Cardiovascular response to poor perfusion causing activation of the renin-angiotensin system (RAAS): Angiotensin II causes vasoconstriction of both afferent and efferent renal arterioles and stimulates release of aldosterone from the adrenal gland.
With this background in mind, we’ll come back to your specific question. Mild congestive heart failure is initially managed with a thiazide diuretic. However, loop diuretics (e.g., furosemide, torsemide, or bumetanide) are the principal drugs used in acute exacerbations.
Loop diuretics inhibit the reabsorption of sodium, chloride, and potassium in the thick ascending limb of Henle’s loop. They are more effective relievers of symptoms as compared to thiazides but do neither class of drugs affect the overall mortality of these patients.
Drugs like B Blockers like Carvedilol, ACE inhibitors like lisinopril and Mineralocorticoid Receptor Antagonists (MRAs) like Spironolactone are given to patients of CHF to reduce overall mortalitity and morbidity due to prolonged activation of RAAS.
B) Hepatic Edema
Patients with advanced liver cirrhosis show an abnormal regulation of extracellular fluid volume, resulting in the accumulation of fluid as ascites or edema. Cirrhosis is the most frequent cause of ascites.
The occurrence of ascites in cirrhosis is due to portal hypertension, which is responsible for:
a) Increase in hydrostatic pressure at the sinusoidal level and
b) The alterations of splanchnic and systemic haemodynamics: Increased splanchnic inflow, reduced systemic resistance and increased plasma volume and cardiac output.
c) Sodium Retention: Which occurs in the setting of increased RAA system and Sympathetic Nervous System activity.
The mechanisms by which portal hypertension leads to the activation of antinatriuretic factors and sodium retention are not completely understood; but there are theories that talk revolve around peripheral arterial vasodilatation.
Now,the million dollar question. What diuretic do we choose here?
Spironolactone is the first diuretic started in patients with cirrhosis, to which other diuretics may be added if response is inadequate.This drug causes a modest diuresis, which is typical of distally acting diuretics. Cirrhotic patients are often very sensitive to intravascular volume depletion. Spironolactone when used alone was as effective as its combined therapy with furosemide . However, this may cause gynecomastia. Amiloride can be used as an alternative, However it is not as effective as spironolactone.
But why, you ask? Well, it turns out, in comparing the efficacy of furosemide and spironolactone in a randomized comparative study, the activity of the renin angiotensin system proved to alter the action of these diuretics. Patients with high renin and aldosterone levels failed to respond to furosemide but were successfully treated with 300 mg per day of spironolactone.
In case of an inadequate response to spironolactone, thiazide diuretics are added to the regimen. Thiazides are terminated if the patient does not respond after 3 days and replaced with a loop diuretic.
Phew! Just hang in there for the last one alright? We’re almost there.
C) Renal Edema:
The leading causes of renal edema are nephrotic and nephritic syndromes. Edema is one of the cardinal clinical features of these syndromes, and may range from localized puffiness to massive anasarca.
The pathophysiological mechanisms of edema formation have been known to be primarily constituted of:
- Abnormal renal sodium retention (primary and secondary).
- Proteinuria causing ENaC activation in Cortical collecting duct (due to loss of plasma albumin)
- Increased capillary wall permeability (related to the release of vascular permeability factor, and other cytokines).
Thus, more than one single mechanism may be responsible for the renal salt retention observed in these diverse conditions.
We already know that the major proportion of filtered Na+ is reabsorbed in the proximal tubule (55%–60%) and in the loop of Henle (25%–30%); only 5%–7% of filtered sodium is reabsorbed in the distal segments of the renal tubular system.
However, in conditions causing renal edema, the efficacy of diuretics acting in proximal segments is hampered by compensatory increase of sodium and water by distal reabsorption in the ascending limb of Henle's loop. Therefore, loop diuretics, which can increase fractional excretion of Na+ up to 30%, remain the first choice for edema treatment in patients with these disorders.
However do keep in mind that due to low serum albumin levels, the diffusion of diuretics in the extracellular compartment is increased. Therefore, a combination of albumin and diuretic may be needed to achieve adequate levels of loop diuretic at the active site.
So keep these key concepts in mind and Urine the clear, mate!
By Dr Abhilasha Sharma
References:
1. Packer M, Cohn JN, Abraham WT. Consensus recommendations for the management of chronic heart failure. Am J Cardiol1999;83:1A–38.
2. Schrier MW, Abraham WT. Hormones and hemodynamics in heart failure. N Engl J Med1999;341:577–85.
3. Wilcox CS. Diuretics. In: Brenner BM, Rector FC, eds. The kidney. Philadelphia: WB Saunders, 1996: 2299–330.
4. Interrelationships between sodium clearance, plasma aldosterone, plasma renin activity, renal hemodynamics and blood pressure in renal disease Klin Wochenschr, 57 (1979), pp. 1273-1285
5. Epstein, M, Levinson, R, Sancho, J, Haber, E, and Re, R. Characterization of the renin-aldosterone system in decompensated cirrhosis. Circ Res. 1977; 41: 818–829
6. Bosch, J, Pizcuetá, P, Feu, F, Fernandez, M, and Garcia-Pagan, JC. Pathophysiology of portal hypertension. Gastroenterol Clin North Am. 1992 Mar; 21: 1–14
7. Sica DA, Gehr TW. Diuretic combinations in refractory oedema states: Pharmacokinetic-pharmacodynamic relationships. Clin Pharmacokinet 1996; 30:229-249.
Comments
Post a Comment