Friday, March 19, 2010

Aldosterone escape versus Aldosterone breakthrough

Fluid and electrolyte deity, Robert Schrier,  had an interesting editorial in Feburary's Nature Reviews: Nephrology (yes, I've gotten a little behind in this blogging business).

Escape versus breakthrough refere to completely different and unrelated concepts related to aldosterone.
  • Aldosterone breakthrough occurs following administration of an ACEi or ARB. ACEi block the conversion of angiotensin I to angiotensin II. The decrease in angiotensin II lowers aldosterone. Angiotensin receptor blockers prevent angiotensis II from from binding receptors through out the vasculature but including the adrenal gland where it prevents aldosterone release. At least that is the plan. In reality about 30-40% of patients given ACEi or ARBs have only a temporary decrease in aldosterone and then after a few weeks, aldosterone returns to pre-treatment levels.  

  • Aldosterone escape is a physiologic phenomenon that occurs with hyperaldosteronism. Aldosterone initially decreases urinary sodium increasing sodium retension contributing to hypertension. This does not result in edema because the sodium retention is short lived. After a short time urinary sodium returns to normal through a process called aldosterone escape. There are two processes that account for this:
    1. Pressure natriuresis. Increased blood pressure decreases distal sodium resorption. The exact mechanism of pressure natriuresis is unknown, it is thought to be mediated by hydrostatic forces. Increased blood pressure is transmitted to the peritubular capillaries, so the resorption of solutes must overcome an elevated hydrostatic pressure gradient. In the face of this increased gradient, sodium resorption falls.
    2. Decreased proximal sodium resorption. Volume expansion decreases proximal sodium reabsorption and increases sodium delivery to the distal nephron and overwelms the aldosterone induced sodium resorption.
The implications of aldosterone escape is that primary hyperaldosteronism does not cause edema. It also explains the delay in hypokalemia found with primary hyperaldosteronism. Aldosterone stimulates potassium excretion but hypokalemia is a late finding in primary hyperaldosteronism. The increased potassium excretion occurs with aldosterone escape when the increased sodium delivery (decreased proximal absorption, i.e. escape) occurs with the increased aldosterone levels.

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