Secondary hyperaldosteronism pathophysiology

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Overview

Secondary hyperaldosteronism is a disease of increasing aldosterone or other mineralocorticoid levels. The resulting Na+ retention produces hypertension, and elevated K+ excretion may cause hypokalemia.

Pathophysiology

Renin-angiotensin system components: Renin 

• The afferent arteriole of each glomerulus contains specialized cells called the juxtaglomerular cells (figure 2). These cells synthesize the precursor, prorenin, which is cleaved into the active proteolytic enzyme, renin. Active renin is then stored in and released from secretory granules [9,10]. Renin initiates a sequence of steps that begins with cleavage of the decapeptide, angiotensin I, from renin substrate (angiotensinogen [AGT]), an alpha-2-globulin produced in the liver (and other organs including the kidney) [11,12]. This first step is also the rate-limiting step of the RAS cascade. Renal hypoperfusion, caused by hypotension or volume depletion, and increased sympathetic activity are the major physiologic stimuli to renin secretion (figure 3).

Renin-angiotensin system components	Secretion control	Measurement	Inhibition
Renin	Baroreceptors (or stretch receptors) in the wall of the afferent arteriole Cardiac and arterial baroreceptors, which regulate sympathetic neural activity and the level of circulating catecholamines, both of which enhance renin secretion via the beta-1-adrenergic receptors The cells of the macula densa in the early distal tubule, which appear to be stimulated by a reduction in chloride delivery, particularly in the chloride concentration in the fluid delivered to this site	The plasma renin activity (PRA) is an indirect measure of renin that employs an enzyme-kinetic bioassay, which measures its capacity to generate angiotensin I. The rate of angiotensin I production, and therefore PRA, is critically dependent upon the concentration of substrate in plasma (ie, angiotensinogen). The plasma renin concentration (PRC) employs a direct immunosorbent assay that detects both prorenin and renin
Angiotensinogen
Angiotensin-converting enzyme
Angiotensin II
Aldosterone

Basic physiology of aldosterone

Circulating aldosterone is principally made in the zona glomerulosa of the adrenal cortex (outer layer of the cortex) by a cascade of enzyme steps leading to the conversion of cholesterol to aldosterone.  

• Aldosterone's production is regulated at two critical enzyme steps:
  • (1) early in its biosynthetic pathway (the conversion of cholesterol to pregnenolone by cholesterol side chain cleavage enzyme) and
  • (2) late (the conversion of corticosterone to aldosterone by aldosterone synthase).

• A variety of factors modify aldosterone secretion--the most important are angiotensin II (AngII), the end-product of the renin-angiotensin system (RAS), and potassium. However ACTH, neural mediators and natriuretic factors also play part in the feedback mechanism. 
• Aldosterone's classical epithelial effect is to increase the transport of sodium across the cell in exchange for potassium and hydrogen ions.

Renin angiotensin system, by Mikael Häggström - https://commons.wikimedia.org/w/index.php?curid=8458370

Adrenal steroid synthesis pathways in adrenal cortex and related enzymes

Pathogenesis

Secondary hyperaldosteronism syndrome is a disease of increasing aldosterone or other mineralocorticoid levels. The resulting Na+ retention produces hypertension, and elevated K+ excretion may cause hypokalemia. Patients with Secondary hyperaldosertonism may have:

• Renin-producing tumors
• Renal artery stenosis
• Cushing syndrome
• Liddle's syndrome
• Ectopic ACTH production
• Licorice ingestion
• Other mineralocorticoids excess:
  • 11 beta hydroxylase deficiency
  • 17 alpha hydroxylase deficiency
  • apparent mineralocorticoid excess