Aldosterone escape
Encyclopedia
In physiology
, aldosterone escape is a term that has been used to refer to 2 distinct phenomena involving aldosterone
that are exactly opposite each other:
In patients with hyperaldosteronism, chronic exposure to excess aldosterone does not cause edema as might be expected. Aldosterone initially results in an increase in Na reabsorption in these patients through stimulation of ENac channels in principal cells of the renal collecting tubules. Increased ENac channels situated in the apical membranes of the principal cells allow for more Na reabsorption which may cause a transient increase in fluid reabsorption as well. However, within a few days, Na reabsorption returns to normal as evidenced by normal urinary Na levels in these patients.
The proposed mechanism for this phenomenon does not include a reduced sensitivity of mineralocorticoid receptors to aldosterone, because low serum potassium is often seen in these patients, which is the direct result of aldo-induced expression of ENac channels. Furthermore, electrolyte homeostasis is maintained in these patients, which excludes the possibility that other Na transporters elsewhere in the kidney are being shutdown. If, in fact, other transporters such as the Na-H antiporter in the proximal tubule or the NaKCl symporter in the thick ascending loop of Henle were being blocked, other electrolyte disturbances would be expected, such as seen during use of diuretics.
Instead, experiments isolating the perfusion pressures seen by glomerular capillaries from heightened systemic pressures due to hyperaldosteronism have shown that Na excretion remains minimal until the kidney is exposed to heightened perfusion pressures. These experiments brought about the proposition that initially high perfusion pressures due to increased Na and water reabsorption in a hyperaldosterone state actually causes of "backflow" of Na and water into the tubules. Normally Na and water are reabsorbed from the tubules and dumped into the interstitium. From there, Starling forces dictate the gradient for movement of water and Na into the peritubular capillaries. Because hydrostatic pressures in the tubules, interstitium and peritubular capillaries are normally equivalent, oncotic pressures govern flow.
Typically, oncotic pressures are higher in the peritubular capillaries, because protein composition in the interstitium is nominal; therefore, Na and water leave the interstitial space and enter the capillaries. When hydrostatic pressures are raised in the peritubular capillaries such as seen in hyperldosteronism, Starling forces begin to favor "backflow" of Na and water from the interstitium into the tubules-- thus, increasing Na excretion. This is the proposed mechanism of "mineralocorticoid escape" for how patients with increased levels of aldosterone are able to maintain Na balance and avoid an edematous state.
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...
, aldosterone escape is a term that has been used to refer to 2 distinct phenomena involving aldosterone
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...
that are exactly opposite each other:
- Escape from the sodiumSodiumSodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
-retaining effects of excess aldosteroneAldosteroneAldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...
(or other mineralocorticoidMineralocorticoidMineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...
s) in primary hyperaldosteronism, manifested by volume and/or pressure natriuresisNatriuresisNatriuresis is the process of excretion of sodium in the urine via action of the kidneys. Natriuresis is promoted by Brain and Atrial natriuretic peptides, and it is inhibited by chemicals such as aldosterone...
. - The inability of ACE inhibitorACE inhibitorACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
therapy to reliably suppress aldosterone release, for example, in patients with heart failure or diabetes, usually manifested by increased salt and water retention. This latter sense may rather be termed refractory hyperaldosteronism.
In patients with hyperaldosteronism, chronic exposure to excess aldosterone does not cause edema as might be expected. Aldosterone initially results in an increase in Na reabsorption in these patients through stimulation of ENac channels in principal cells of the renal collecting tubules. Increased ENac channels situated in the apical membranes of the principal cells allow for more Na reabsorption which may cause a transient increase in fluid reabsorption as well. However, within a few days, Na reabsorption returns to normal as evidenced by normal urinary Na levels in these patients.
The proposed mechanism for this phenomenon does not include a reduced sensitivity of mineralocorticoid receptors to aldosterone, because low serum potassium is often seen in these patients, which is the direct result of aldo-induced expression of ENac channels. Furthermore, electrolyte homeostasis is maintained in these patients, which excludes the possibility that other Na transporters elsewhere in the kidney are being shutdown. If, in fact, other transporters such as the Na-H antiporter in the proximal tubule or the NaKCl symporter in the thick ascending loop of Henle were being blocked, other electrolyte disturbances would be expected, such as seen during use of diuretics.
Instead, experiments isolating the perfusion pressures seen by glomerular capillaries from heightened systemic pressures due to hyperaldosteronism have shown that Na excretion remains minimal until the kidney is exposed to heightened perfusion pressures. These experiments brought about the proposition that initially high perfusion pressures due to increased Na and water reabsorption in a hyperaldosterone state actually causes of "backflow" of Na and water into the tubules. Normally Na and water are reabsorbed from the tubules and dumped into the interstitium. From there, Starling forces dictate the gradient for movement of water and Na into the peritubular capillaries. Because hydrostatic pressures in the tubules, interstitium and peritubular capillaries are normally equivalent, oncotic pressures govern flow.
Typically, oncotic pressures are higher in the peritubular capillaries, because protein composition in the interstitium is nominal; therefore, Na and water leave the interstitial space and enter the capillaries. When hydrostatic pressures are raised in the peritubular capillaries such as seen in hyperldosteronism, Starling forces begin to favor "backflow" of Na and water from the interstitium into the tubules-- thus, increasing Na excretion. This is the proposed mechanism of "mineralocorticoid escape" for how patients with increased levels of aldosterone are able to maintain Na balance and avoid an edematous state.