83. Mineralocorticoids

Question 1

Mineralocorticoids

Answer 1

-Aldosterone
It is the main mineralocorticoid hormone. It can be produced only in the most superficial layer (z. glomerulosa) of the adrenal cortex, because 18 aldehyde oxalalse (aldolase) enzym can only be found here.

Mineralocorticoids regulate electrolyte and water metabolism by acting mainly on the distal convoluted tubule of the kidney.

The main effect is the reabsorption of sodium ions and secretion of potassium ions. To manifest the effect, new proteins have to be synthesized, therefore the effect is exerted only from approx. 45 minutes after the production of the hormone.

As an effect of aldosterone, synthesis of potassium and sodium transporters and potassium/sodium ATPases (pumping proteins) are increased in tubular cells of the kidney.

Question 2

Overdose of mineralocorticoids

Answer 2

In case of overdosage, reabsorption of Na+ increases. Water is also reabsorbed with Na+. The result is isoosmotic hypervolemia. 20 -25%.

Urinary excretion, however, also increases because of the rising blood pressure, so the level of hypervolemia will return to 10%.

This phenomenon is usually referred to as “renal escape”. In humans, arterial blood pressure increases (primary hyperaldosteronism).

K+ content of the body decreases. As a result of this, muscular weakness develops.
In the lack of K+, paradox alkalosis occurs, because the kidney is able to reabsorb K+ against a H+ (this occurs only in serious K+ insufficiency.

Question 3

Mineralocorticoid deficiency

Answer 3

In the lack of mineralocorticoids, excretion of K+ and H+ decreases, resulting in mild acidosis and accumulation of K+.

High K+ - damaging effect on cardiac function.

The accumulation of K+ in the body will lead to the elevation of K+ concentration inside the cells. This will increase the osmotic water intake of the cells, causing IC hypervolemia.

Loss of Na+ and Cl- increases. The body loses water with Na+, and extracellular hypovolemia may reach the level of 20-25%.
Parallel with the loss of Na+, also the absorption of Na+ decreases in the intestines, which causes vomiting and diarrhea. This leads to further loss of water, amount of circulating blood decreases and blood pressure declines.

Arterioles constrict in order to maintain normal blood pressure. Thus, the oxygen supply of the capillaries worsens. Without oxygen, vessels dilate after a period of time. The consequent blood pressure decrease, makes the K+ caused cardiac failure.

At the end, blood flow through the kidney decrease, resulting in azotemia and the death of the animal.

Question 4

Regulation of mineralocorticoids

Answer 4

The four major factors of the regulation:

1. Increase of plasma K+ concentration. Increase of K+ = increase of aldosterone synthesis.

(Rapid responsive capability is necessary, because elevation of K+ level leads to cardiac death while the decrease of potassium leads to muscular paralysis.
Most important regulator, rapid reactive ability)

2. Renin-angiotensin system.
   The system is activated when juxtaglomerular apparatus (JGA) detects Na+ deficiency. First angiotensin II, then aldosterone is synthesized
3. Decrease of the Na+ content of the body activates the synthesis of mineralocorticoids.
   This is a part of the volume regulation.
   (Other effects, such as salt deprivation, salt and water deprivation, standing posture, congestion, sweating, rises of body temperature, stress, etc., also belong to these processes.)
4. ACTH has a mainly permissive effect. In case of ACTH deficiency, z.glomerulosa becomes thinner by 50%, but aldosterone synthesis is not terminated.