Aldosterone Physiology & Hyperaldosteronism

Aldosterone is the primary mineralocorticoid and is secreted from the zona glomerulosa. For more on the biosynthesis of aldosterone, click here: adrenal cortex hormones Aldosterone maintains body fluid and electrolyte homeostasis. Its secretion is regulated primarily by angiotensin II, serum potassium levels, and ACTH. We can distinguish between two forms of hyperaldosteronism, depending on the cause:

• In primary hyperaldosteronism, excessive secretion from the adrenal gland is autonomous; for example, an aldosterone-secreting tumor.
• In secondary hyperaldosteronism, excessive aldosterone secretion is the result of excessive renin secretion.

Hyperaldosteronism is an important cause of secondary hypertension – thus, detection and treatment are key to minimizing cardiovascular damage. Treatment can be surgical or medical. In a healthy individual, aldosterone maintains normal blood volume and electrolyte balance. Key anatomical structures in the renin-angiotensin II- aldosterone feedback loop:

• The kidney, which senses changes in blood pressure.
• Nephron with the glomerulus and the presence of the juxtaglomerular cells near the afferent arteriole (click here for glomerular details).
• Liver and indicate that it produces angiotensinogen.
• Lungs; their vascular endothelium is an important site for production of angiotensin converting enzyme (ACE).
• Adrenal gland and show that it produces aldosterone.

1. Low blood volume produces reduced renal perfusion pressure. In response, the juxtaglomerular cells release renin, which is the enzyme that converts angiotensinogen to angiotensin I. ACE then converts angiotensin I to angiotensin II. 2. Angiotensin II triggers release of aldosterone from the adrenal gland. 3. Aldosterone increases the insertion of ENaCs (epithelial sodium channels) in the distal nephron. 4. As a result, sodium and water retention increases. In turn, sodium reabsorption produces a negative electrochemical gradient that allows for potassium and, ultimately, hydrogen ion loss (for a review of reabsorption and secretion in the nephron, see the links in our notes). 5. Because sodium and water are retained, blood volume increases. In a healthy person, the return to normotension will "turn off" juxtaglomerular renin release. Some additional stimuli and inhibitors for aldosterone secretion:

• Hyperkalemia, ACTH, and catecholamine-stimulated release of renin trigger aldosterone release.
• Hypokalemia, atrial natriuretic peptide (ANP), dopamine, and heparin inhibit aldosterone release.

The origins of this disorder lie within the adrenal cortex, itself. Thus, aldosterone levels are increased, and, via negative feedback, renin activity is reduced ; the ratio of plasma aldosterone concentration to plasma renin activity is elevated (PAC:PRA). Initially, increased aldosterone and subsequent sodium and water retention increases extracellular fluid and blood pressure. However, these effects are not as pronounced as we might expect because, within a few days, sodium and water excretion resumes due to what's called the "aldosterone escape." Aldosterone escape: The "aldosterone escape" explains why patients with primary aldosteronism do not typically present with edema, which we would otherwise expect from excessive aldosterone exposure. Although not completely understood, the aldosterone escape is thought to work via a few mechanisms, all of which increase sodium and water excretion:

• ANP increases glomerular filtration rate and downregulates sodium transporters and channels.
• Thiazide-sensitive sodium-chloride co-transporters are downregulated,
• Pressure natriuresis, by which increased renal perfusion leads to increased sodium excretion.

Other effects of excessive aldosteronism include:

• Hypokalemia, because sodium reabsorption produces an electronegative lumen that favors potassium loss in the urine.
• Alkalosis, due to hydrogen ion loss – in response to hypokalemia, hydrogen is secreted to allow for more potassium reabsorption.

Ultimately, a new steady state is established with increased extracellular fluid volume and decreased plasma potassium. However, most patients are only mildly hypokalemic, if at all, thanks to modern screening techniques. Normokalemic hypertension is the most common presentation of primary aldosteronism.

• This is because we now rely on ratios of plasma aldosterone to renin activity (PCA:PRA) for screening, which allows for earlier detection, rather than the classic triad of hypertension, hypokalemia, and alkalosis.

The most common causes of primary aldosteronism are:

• Adenoma, which can be treated with surgical removal of the tumor
• Bilateral idiopathic hyperplasia, which is treated medically with spironolactone or eplerenone.
• Less common causes include: unilateral hyperplasia, carcinoma, and familial forms of aldosteronism.

• Patients may experience tiredness, weakness, headaches, and polyuria.
• Hypertension, especially new and/or hypertension that is resistant to treatment, is common – and often the most salient sign of primary aldosteronism.
• Left ventricular hypertrophy is a potential outcome.
• We also worry about the development of chronic kidney disease in these patients.

Characterized by increased aldosterone and increased renin. The ratio of plasma aldosterone concentration to plasma renin activity is elevated, but less so than in primary aldosteronism.

• Disorders that result in increased renin activity, including:

Renal ischemia, low intravascular volume resulting from heart failure or cirrhosis, sodium-wasting disorders, juxtaglomerular hyperplasia, and renin-secreting tumors.

• Heart failure and cirrhosis will result in edema in these patients.

Similar to PAI Patients may be hypertensive or hypotensive, depending on the etiology. For references, please see full tutorial.