MINERALCORTICOIDS

1. FUNCTIONS OF
MINERALCORTICOIDS-ALDOSTERONE
PREPARED BY FATIMA SUNDUS

2. FUNCTIONS OF THE MINERALOCORTICOIDS— ALDOSTERONE
• 90% of mineralocorticoid activity is provided by aldosterone
• It is very essential for life and it maintains the osmolarity and volume of
ECF.
• It is usually called life-saving hormone because, its absence causes death
within 3 days to 2 weeks.

3. Aldosterone Is the Major Mineralocorticoid Secreted by
the Adrenals.
Cortisol can also bind to mineralocorticoid receptors with high affinity.

4. However, the renal epithelial cells express the enzyme 11β-hydroxysteroid
dehydrogenase type 2 (11β-HSD2), which has actions that prevent cortisol from
activating mineralocorticoid receptors.
One action of 11β-HSD2 is to convert cortisol to cortisone, which does not
avidly bind mineralocorticoid receptors.
In patients with genetic deficiency of 11β-HSD2 activity, cortisol may have
substantial mineralocorticoid effects.
This condition is called apparent mineralocorticoid excess syndrome (AME)
because the patient has essentially the same pathophysiological changes as a
patient with excess aldosterone secretion, except that plasma aldosterone levels
are very low in the patient with AME.

5. RENAL AND CIRCULATORY EFFECTS OF ALDOSTERONE
Aldosterone Increases Renal Tubular Reabsorption of Sodium and
Secretion of Potassium.

7. Aldosterone has three important functions.
It increases:
1. Reabsorption of sodium from renal tubules
2. Excretion of potassium through renal tubules
3. Secretion of hydrogen into renal tubules.

8. On Sodium Ions
Acts on the distal convoluted tubule and the collecting duct and increases
the reabsorption of sodium.
During hypersecretion of aldosterone, the loss of sodium through urine is
only few milligram per day.
But during hyposecretion of aldosterone, the loss of sodium through urine
increases (hypernatriuria)

9. On Extracellular Fluid Volume
When sodium ions are reabsorbed from the renal tubules, simultaneously water is
also reabsorbed.
Water reabsorption is almost equal to sodium reabsorption; so the net result is the
increase in ECF volume.

10. On Blood Pressure
Increase in ECF volume and the blood volume finally leads to increase in
blood pressure.
The rise in arterial pressure then increases kidney excretion of both
sodium and water, called pressure natriuresis and pressure diuresis,
respectively

11. Excess Aldosterone Increases Extracellular Fluid Volume and Arterial
Pressure But Has Only a Small Effect on Plasma Sodium Concentration;
aldosterone deficiency causes hyponatremia.
Reabsorption of ions also leads to reabsorption of water- net result is increase in
ECF volume.--increase in ECF volume & blood volume- increase in blood
pressure.
When aldosterone is deficient, the K+ concentration in ECF increases
hyperkalemia.
Arterial pressure kidney excretion of salt (pressure natriuresis) and water
(pressure diuresis).

12. Excess Aldosterone Causes Hypokalemia and Muscle Weakness
Aldosterone Deficiency Causes Hyperkalemia and Cardiac Toxicity
Excess Aldosterone Increases Tubular Hydrogen Ion Secretion and
Causes Alkalosis.
aldosterone stimulates sodium and potassium transport in sweat glands,
salivary glands, and intestinal epithelial cells

13. CELLULAR MECHANISM OF ALDOSTERONE ACTION
First, because of its lipid solubility in the cellular membranes, aldosterone
diffuses readily to the interior of the tubular epithelial cells.
Second, in the cytoplasm of the tubular cells, aldosterone combines with a
highly specific cytoplasmic mineralocorticoid receptor (MR) protein

14. Third, the aldosterone-receptor complex or a product of this
complex diffuses into the nucleus, and attach with DNA to form one or
more types of messenger RNA (mRNA)
Fourth, the mRNA diffuses back into the cytoplasm, where, operating
in conjunction with the ribosomes, it causes protein formation.

16. POSSIBLE NONGENOMIC ACTIONS OF ALDOSTERONE AND OTHER
STEROID HORMONES
aldosterone has been shown to increase formation of cyclic adenosine
monophosphate (cAMP) in vascular smooth muscle cells and in epithelial
cells of the renal collecting tubules
In other cell types, aldosterone has been shown to rapidly stimulate the
phosphatidylinositol second messenger system

17. REGULATION OF ALDOSTERONE SECRETION
Regulation of aldosterone secretion by the zona glomerulosa cells is almost
entirely independent of regulation of cortisol and androgens by the zona
fasciculata and zona reticularis.

18. The following four factors are known to play essential roles in regulation of
aldosterone:
1. Increased potassium ion concentration in the extracellular fluid greatly
increases aldosterone secretion.
2. Increased angiotensin II concentration in the extracellular fluid also
greatly increases aldosterone secretion.
3. Increased sodium ion concentration in the extracellular fluid very slightly
decreases aldosterone secretion.
4) Increased atrial natriuretic peptide (ANP), a hormone secreted by the
heart when specific cells of the cardiac atria streched, decreased
aldosterone secretion.
4. ACTH from the anterior pituitary gland is necessary for aldosterone
secretion but has little effect in controlling the rate of secretion in most
physiological conditions