Adrenals Salt and Water Balance principal control of angiotensin II ACTH mg day Hormones secreted by the zona glomerulosa secretes mineralocorticoids steroid hormone in low amounts aldosterone 100 150 micrograms day under the Hormones secreted by the zona fasciculata secretes glucocorticoids steroid hormone in relatively high amounts cortisol 10 20 mg day under the control of Hormones secreted by the zona reticularis secretes adrenal androgens steroid hormone in relatively high amounts DHEA DHEAS androstenedione 20 Hormones secreted by the adrenal medulla chromaffin cells secrete catecholamines epinephrine and norepinephrine under the control of the sympathetic nervous system acetylcholine Regulation of aldosterone secretion Renin Angiotensin Aldosterone System RAAS Renin secreted by juxtaglomerular cells in the kidney in response to Drop in blood pressure Drop in sodium concentration sensed by macula densa cells of distal convoluted tubule Renin converts precursor angiotensinogen into angiotensin I Angiotensin Converting Enzyme ACE converts inactive angiotensin I into active angiotensin II Angiotensin II maintains extracellular fluid volume and blood pressure Increases aldosterone secretion from the zona glomerulosa via increased transcription of CYP11B2 aldosterone synthase Also constricts vascular smooth muscle releases catecholamines from adrenal medulla promotes release of vasopressin Functions of aldosterone saves sodium loses potassium Sodium retention increases fluid volume osmolarity blood pressure Aldosterone is released from the glomerulosa cells enters the blood binds to mineralocorticoid receptors MR in the renal distal tubule cid 127 MR Aldosterone complex binds to the DNA and acts as a transcription factor for proteins that save sodium and excrete potassium Na K ATPase K channels Mineralocorticoid insufficiency defects in aldosterone synthesis action Adrenocortical failure Addison s disease Low blood pressure low plasma sodium raised plasma potassium Congenital adrenal hyperplasia caused by 21 hydroxylase deficiency Virilization due to increased adrenal androgens Addisonian crisis after birth due to increased DOC causes repression of renin and aldosterone Mineralocorticoid excess Conn s syndrome hypertension and low plasma potassium due to aldosterone secreting adrenal tumor High aldosterone in the presence of suppressed renin Treated with antihypertensives potassium supplements surgery to remove tumor In the case of bilateral adrenal hyperplasia patients are managed with aldosterone antagonists cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 Spironolactone is used to treat hyperaldosteronism antagonist for MR Mineralocorticoid symptoms of cortisol overproduction the MR and GR are homologs and the MR binds cortisol preferentially specificity is conferred by metabolism of cortisol via HSD 11B2 which inactivates cortisol to cortisone In excess production of cortisol Cushing s more cortisol is produced than can be metabolized so the excess binds to and activates MR causing high blood pressure Cushing s syndrome Tumors of the zona fasciculata of the adrenal cortex may secrete unregulated amounts of cortisol resulting in Cushing s syndrome Increased appetite weight gain fat synthesis muscle wasting and weakness poor wound healing red stretch marks on skin high blood pressure high blood glucose Vasopressin antidiuretic hormone changes in plasma osmolarity increased solute concentration affect ADH secretion ADH promotes insertion of aquaporins into the distal tubules and collecting ducts which become permeable to water resulting in water being reabsorbed rather than secreted in the urine Atrial natriuretic peptide ANP promotes sodium excretion and lowers blood pressure Increased venous return due to high blood pressure causes increased stretch of atrial cardiomyocytes which secrete ANP Vasodilation decreases blood pressure Decreases RAAS activity Inhibits sodium reabsorption natriuresis which causes formation of dilute urine diuresis Hormone Blood volume Sodium Potassium Blood pressure Aldosterone Angiotensin II Vasopressin ANP Increase Increase Increase Decrease Retain Retain Retain Excrete Excrete Excrete Excrete Retain Water Retain Retain Retain Excrete Increase Increase Increase Decrease Adrenal Medulla Synthesis of catecholamines synaptic vesicles synaptic vesicles What is a chromaffin cell Chromaffin cells are the catecholamine secreting cells of the adrenal medulla Chromaffin cells synthesize norepinephrine from the precursor dopamine by the catalytic action of an enzyme called dopamine beta hydroxylase in the Dopamine is produced in the cytoplasm of the nerve terminal from DOPA by the enzyme DOPA decarboxylase and is then actively transported into the DOPA is produced from tyrosine by the enzyme tyrosine hydroxylase rate limiting step Chromaffin cells also contain the enzyme PNMT which methylates norepinephrine in the cytoplasm to epinephrine which is then taken up by other vesicles and stored in the nerve terminals The adrenal medulla and the sympathetic nervous system the adrenal medulla is a modified ganglion which is stimulated by the sympathetic nervous system fight or flight catecholamine release is stimulated by cholinergic neurons release Ach cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 cid 127 2nd messenger Target Phospholipase C IP3 DAG Contract smooth muscle Decreased cAMP Increased cAMP Increased cAMP Inhibit norepinephrine release Contract cardiac muscle GI sphincters Smooth muscle relaxation metabolic effects Increased cAMP Brown adipose tissue metabolism in newborns Epinephrine release Stimulated by stress low blood pressure hemorrhage pain low blood glucose exercise surgery asphyxia etc through activation of the fight or flight response of the sympathetic nervous system Pheochromocytoma paraganglioma Pheochromocytoma chromaffin tumor that secretes excessive amounts of catecholamines causes high blood pressure chest pain palpitations headache Paraganglioma catecholamine secreting tumor in an ectopic location cid 127 MEN2 VHL NF1 increase likelihood of these tumors Adrenergic receptors Receptor alpha 1 alpha 2 beta 1 beta 2 beta 3 etc Thyroid Structure and function Thyroid functional unit follicle Composed of epithelial follicular cells and colloid Parafollicular cells produce calcitonin Thyroid hormone