Mineralocorticoid (Aldosterone)
Mineralocorticoid
(Aldosterone) Mineralocorticoids are the strongest naturally mineralocorticoids
Relation b/w Aldosterone and ADH
- Aldosterone from adrenal gland --> increased Na+ --> plasma osmolarity sensed by osmoreceptors in hypothalamus: osmoreceptors will signal --> hypothalamus --> ADH to post. pit. --> ADH --> collecting duct --> H2O --> decreased Na+, decreased plasma osmolarity ALDOSTERONE is important for regulation of increased [Na+ in total body], where ADH regulates the plasma Na+ concentration
Mechanics of aldosterone action:
- Aldosterone stimulates active transport of Na++ through epithelial cell - Aldosterone, like other steroid hormones, induces synthesis of proteins and the proteins are involved in following functions: 1) Increased Na+ transport by opening the Na+ channels in distal convoluted tubule 2) Increased number of Na-K ATPase molecules 3) May alter the membrane phospholipid composition
Regulation of Aldosterone
- Renin-angiotensin system regulates the secretion of aldosterone - aldosterone isnt dependent on ACTH, but ACTH required for normal levels - the stimulatory controllers are sensed by juxtaglomerular cells in the kidney , which secrete an enzyme called renin. A) decrease in BV causes a decrease in renal perfusion, which increases renin secretion. B) Angiotensin II acts on zona glomerulosa cells to increase conversion of corticosterone to aldosterone C) Aldosterone --> increased Na --> increased volume of ECF --> blood volume
Hypocalcemia
- abnormally low level of calcium in the blood - prolonged ST and QT intervals
Hypercalcemia
- the presence of abnormally high levels of Ca in blood - short ST segment and wide T wave
Clinical symptoms
1) Hypertension (aldosterone increases Na+ reabsorption) 2) Hypokalemia (aldosterone increases K+ secretion) 3) Metabolic alkalosis (b/c aldosterone decreases H+ secretion) 4) General symptoms of fatigue and weakness, polyuria 5) Decreased renin secretion (b/c increased aldosterone)
Functions of aldosterone:
1) Renal Na+ retention (absorption) 2) Na+ intake low- increased renin secretion - increase in plasma angiotensin II, which stimulates aldosterone secretion - also, Na+ reabsorption in sweat glands, colon. - increased renal K+, NH4, and H4 secretion
Why cortisol does not bind to mineralocorticoid receptors in the kidneys and other locations and produce mineralocorticoid effects?
Kidneys and other aldosterone sensitive tissues contain the enzyme 11-B hydrosteroid dehydrogenase-2. This enzyme leaves aldosterone untouched, but it converts cortisol --> corticosterol --> II-oxy derivative (do not bind to receptors)
Conn's Syndrome
Primary aldosteronism, - aldosterone secreting adenoma, which is unilateral (75%) and 25% cases are bilateral adrenal hyperplasia
Transport of Aldosterone
Transport in blood, aldosterone binds with low affinity to plasma albumin, transcortin and specific aldosterone globulin.
Treatment for 1 and 2 aldosteronism
aldosterone antagonist (high doses)
Secondary Aldosteronism
any cause of low blood volume (hemorrhage, dehydration) leads to increased renin and aldosterone secretion
Primary Aldosteronism
caused by aldosterone secreting tumors
Hyperaldosteronism
clinical state that results from increased aldosterone
Hypokalemia
deficient level of potassium in the blood - ST depression - prominent U wave, shallow, flat inverted T wave
Hyperkalemia
excessive potassium in the blood - tall peaked T waves, flat P waves, wide QRS complex, and prolonged PRI interval
Atrial Natriuretic Peptide
A peptide hormone secreted by cardiac atrial cells in response to atrial distension (increased blood flow); causes increased renal sodium excretion and as such lowers blood pressure (antagonizing aldosterone). ANF inhibits aldosterone production