The Adrenal Glands Located above kidneys Adrenal medulla inside is innervated by sympathetic nervous system Adrenal cortex outside is composed of three structural layers each of which forms secretes a different hormone o Zona Glomerulosa mineralcotricoids ex aldosterone o Zona fasciculate glucocorticoids ex cortisol o Zona reticularis androgens sex hormones Women under a long term stress lose their hair because they produce a lot of androgens which can cause male pattern baldness Hormones of the adrenal cortex are steroid hormones and all are produced from cholesterol There are many intermediates so enzyme mutations can prevent conversion from a precursor This will lead to an abundance of the other cortex hormones Mostly regulated by negative feedback There is no set point because levels fluctuate throughout the day determined by higher brain centers Adrenal medulla Produces opioid peptides enkephalins o natural pain killers o inhibit the nociceptor pain pathway Produces catecholamines epinephrine and norepinephrine Sympathetic nervous system releases acetylcholine which innervates chromaffin cells to secret epi and norepi Actions are identical to the neurotransmitters but these travel through the bloodstream Help deal with short term stress o Increase heart rate blood pressure blood glucose o Bronchodilation o Decrease blood flow function of GI tract o Increase blood flow to skeletal muscle Epi and norepi bind adrenergic receptors with relative affinities o Norepi 1 and 2 o Epi 2 o Equal for 1 and 3 1 Gq PLC IP3 Ca2 binds calmodulin Smooth muscle contraction GI vasoconstriction sphincter contraction Radial muscle contraction leads to pupil dilation can see more in peripheral vision 2 Gi adenylyl cyclase decr cAMP Inhibits insulin secretion to increase blood glucose Inhibits digestive secretions Fat cell lipolysis for ATP energy 1 Gs activate adenylyl cyclase incr cAMP increases myocardial activity stroke volume blood pressure increase SA firing rate to increase heart rate fat call lipolysis renin release by kidneys 2 Gs activate adenylyl cyclase incr cAMP bronchodilation smooth muscle relaxation bladder wall to hold more urine liver gluconeogenesis and glycogenolysis to increase blood glucose 3 Gs activate adenylyl cyclase incr cAMP mostly located on fat cells enhances lipolysis Epi action on SA node SA node contains autorhythmic cells but can also be controlled by the autonomic and endocrine systems epi binds 1 Increase open funny channels IF and Ca channels open Increase rate of spontaneous depolarization at threshold contraction occurs thus heart rate increases Beta blockers act as antagonists to decrease heart rate allowing it to fill with more blood This causes the heart to stretch and produce more forceful contractions Beta blockers have side effects because receptors are located throughout the body Hypersecretion can lead to paroxysmal HTN blurred vision tinnitus diaphoresis palpitations stroke aneurysm arrhythmias MI can be caused by pheochromocytoma which may ultimately need surgical removal to correct Hypersecretion generally is asymptomatic because it is compensated for by the sympathetic nervous system and corticosteroids Adrenal cortex Aldosterone Cortisol Androgens Aldosterone Increases osmolarity when needed by increasing sodium reabsorption Blood pressure is the driving force for glomerular filtration o Renin is produced by juxtaglomerular cells when blood pressure Na concentration is low converts angiotensinogen into angiotensin I which is converted to angiotensin II by ACE angiotensin converting enzyme o Angiotensin II causes vasoconstriction and stimulates aldosterone release o People with HTN take ACE inhibitors to prevent this Production stimulated by o Angiotensin II o Renin indirectly Production inhibited by o atrial natriuretic peptide ANP o osmolarity or Na increases Bound to cortisol binding globulin CBG or albumin in circulation then enters tubule cells of kidney Activates cystolic mineralocorticoid receptor Aldosterone binds receptor Translocation into nucleus Homodimerization Bind to glucocorticoid response elements GRE in promoters Increase gene transcription to stimulate Na K pump and channel synthesis This receptor binds aldosterone and cortisol with equal affinity Cortisol concentration is thousands fold higher than aldosterone Target cells for aldosterone express 11 beta hydroxysteroid dehydrogenase 2 HSD2 which converts cortisol to cortisone Cortisone has a very weak affinity for mineralocorticoid receptor Licorice contains glycyrrhetinic acids which inhibit 11 HSD2 With excess licorice consumption cortisol is not converted to cortisone and therefore acts on the MR called aspseudohyperaldosteronism Because cortisol is so high and it mimics the effect of aldosterone this can cause hypertension and hypokalemia Aldosterone stimulates opening of sodium and potassium channels on the apical membrane synthesis of new Na and K channels on apical membrane synthesis and insertion of Na K pumps on basolateral membrane Together increases Na in blood Water follows salt thus BP increases Aldosterone is both an antagonist and additive to ADH based on stimulus If BP and blood volume are low ADH and aldosterone are secreted together If osmolarity is abnormal they act in opposition to each other o ADH increases water reabsorption so BP increases but osmolarity decreases o Aldosterone increases Na reabsorption so osmolarity increases Then water follows so BP increases ANP is released from the atrium in response to wall stretching which occurs when BP is too high ANP increases sodium excretion to decrease blood pressure Hyperaldosteronism aka Conn s syndrome or aldosteronism symptoms include Hypernatremia hypervolemia Hypokalemia Hypertension Primary is often caused by adrenal cortical adenoma Secondary is due to activity of renin angiotensin system May also be due to defect in the enzyme 17 hydroxylase which allows synthesis of other adrenal cortex hormones In the absence of those hormones the concentration of aldosterone increases Hypoaldosteronism symptoms include Hyponatremia hypovolemia Hyperkalemia Hypotension May be caused by primary adrenal insufficiency but more likely due to a person taking ACE inhibitors Cortisol Produced in response to stress Helps resist long term stressors o Boosts blood pressure o Mobilizes energy stores o Suppresses immune system inflammatory response Mainly bound to corticosteroid binding globulin CBG in circulation which