Dr. Omary Chillo (MD, PhD) Adrenal Gland 06/04/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Adrenal Glands A.K.A – Suprarenal Glands 06/04/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) 80% Cortex Medulla 20% Catecolamines Androgens Zona Reticularis Glucocorticoids Zona Fasciculata Mineralocorticoids Zona Glomerulosa 06/04/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Adrenal Cortex The largest part of the adrenal gland Secretes adrenocortical hormones – steroid hormones Zona Reticularis Androgens dehydroepiandrosterone Musculin effect androstenedione Estrogen, glucocorticoids Zona Fasciculata Glucocorticoids Cortisol Blood Glucose Corticosterone Androgens Zona Glomerulosa Mineralocorticoids Aldosterone Sodium and Potassium 06/04/2019 Dr. Omary Chillo (MD, PhD)

Synthesized in zona glomerulosa Functions of Mineralocorticoids Synthesized in zona glomerulosa Regulate the electrolyte concentrations of extracellular fluids Aldosterone – most important mineralocorticoid Maintains Na+ balance by reducing excretion of sodium from the body Stimulates reabsorption of Na+ by the kidneys and K+ excretion 06/04/2019 Dr. Omary Chillo (MD, PhD)

The Five Mechanisms of Aldosterone Secretion Renin-angiotensin mechanism – kidneys release renin, which is converted into angiotensin II that in turn stimulates aldosterone release Plasma concentration of potassium – directly influences the zona glomerulosa cells. Increased sodium conc. in the extracellular fluid slightly decrease aldosterone level. ACTH – causes small increases of aldosterone during stress Atrial natriuretic peptide (ANP) – inhibits activity of the zona glomerulosa 06/04/2019 Dr. Omary Chillo (MD, PhD)

Actions of Aldosterone Stimulates sodium reabsorption by distal tubule and collecting duct of the nephron and promotes potassium and hydrogen ion excretion Increases transcription of Na/K pump Increases the expression of apical Na channels and an Na/K/Cl cotransporter 06/04/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Action of Aldosterone 06/04/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Excess Aldosterone Leads Hypokalemia Muscle weakness – Impairment of AP transmission Mild Alkalosis (Na+ and H+ exchange) Expands ECF volume hence increase blood pressure Small effect on plasma sodium concentration 06/04/2019 Dr. Omary Chillo (MD, PhD)

Too little Aldosterone Causes Hyperkalemia Cardiac Toxicity – Weakness of heart muscles, arrhythmias and heart failure. Decreased ECF volume and blood pressure 06/04/2019 Dr. Omary Chillo (MD, PhD)

Effect of Aldosterone on other body organs Sweat Glands Salivary Glands Intestinal Epithelial 06/04/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Glucocorticoids Mineralocorticoid Glucocorticoid Sex steroids 06/04/2019 Dr. Omary Chillo (MD, PhD)

Diurnal Variation of Glucocorticoids % Change +100 8-10 am Note: Related to sleep-Wake Cycle -100 2 am 12 Midnight 12 Noon 12 Midnight LKS 06/04/2019 Dr. Omary Chillo (MD, PhD)

Hypothalamic-Pituitary-Adrenal (HPA) Axis ACTH binds receptors on surface of cells in zona fasciculata of adrenal cortex – cAMP second messenger increases production of glucocorticoid from cholesterol 06/04/2019 Dr. Omary Chillo (MD, PhD)

Target Tissues of Glucocorticoids Liver Skeletal Muscle Adipose Tissue Bone Brain Skin Retina Kidneys Heart Lymphoids Smooth Muscle Lung Stomach Intestines Fibroblast Testes 06/04/2019 Dr. Omary Chillo (MD, PhD)

Physiological Effects 1. Metabolic Effects: Catabolic, glucose 2. Antiinflammatory and Immunosuppressive Effects 06/04/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Metabolic effects Glucose Influence carbohydrate and fat metabolism to ensure adequate delivery of glucose to the brain Increase gluconeogenesis, decrease peripheral use of glucose Fat Increase in free fatty acids (increased lipolysis) Redistribution of fat from the extremities to the trunk and face (buffalo hump) Protein Favors protein breakdown and helps mobilize amino acids to the liver for gluconeogenesis 06/04/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Anti-inflammatory and immunosuppressant activity Increase in circulating levels of neutrophils by interfering with adhesion Decrease in eosinophils, lymphocytes, and monocytes Decrease leukocyte migration, and phagocytic activity Decrease production of phospholipase A2, prostaglandins, thromboxanes and leukotrienes 06/04/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Other Effects 1. Electolytes: Decrease absorption of Ca2+ from the intestine and increase renal excretion of Ca2+ Increased Na+ and H2O reabsorption, increased K+ excretion 2. Cardiovascular effects: Facilitates the effects of catecholamine, Maintenance of BP 3. Respiratory: Facilitates action of catecholamines (relax airway smooth muscle) Fetal lung maturation, increased surfactant secretion 4. CNS Effects: mood, sleep patterns 06/04/2019 Dr. Omary Chillo (MD, PhD)

Abnormalities of adrenocortical secretion Addison’s disease Hypoadrenalism – Mainly due to autoimmunity against the cortices, which leads to atrophy Decreased ECF volume Decreased Na+ tubular reabsorption Hyperkalemia Impaired glucose mobilization Stress effect deterioration Highly susceptible to infections Melanin pigmentation of mucous membranes 06/04/2019 Dr. Omary Chillo (MD, PhD)

Abnormalities of adrenocortical secretion Cushing’s disease Hyperadrenalism – Can be due to, tumors of the anterior pituitary or adrenal cortex, ectopic ACTH release, hypersecretion of CRH by hypothalamas Mainly attributed by hypersecretion of cortisol Increased blood glucose concentration Muscle weakness and osteoporosis due to protein mobilization Suppressed immunity Increased blood pressure in 80% of patients Buffalo torso 06/04/2019 Dr. Omary Chillo (MD, PhD)

Abnormalities of adrenocortical secretion Adrenogenital Syndrome Adrenocortical tumor secreting excessive androgens Mainly attributed by hypersecretion of androgens Can be easily detected during childhood Leads to muscularizing effect 06/04/2019 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Thanks 06/04/2019 Dr. Omary Chillo (MD, PhD)