FUNCTIONS OF MINERALCORTICOIDS.pptx

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 11 β- 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.

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

7. 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 )

8. 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 .

9. 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

10. 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).

11. 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

12. 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

13. 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 .

14. 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

15. 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 .

16. The following four factors are known to play essential roles in regulation of aldosterone : 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