ADRENAL MEDULLA & STRESS RESPONSE Lecture – 3 Dr. Zahoor Ali Shaikh

ADRENAL MEDULLA Adrenal Medulla is a specialized ganglion of sympathetic autonomic nervous system. Adrenal Medulla consists of modified postganglionic sympathetic neurons called CHROMAFFIN CELLS, because of their staining preference for chromium ions.

ADRENAL MEDULLA Preganglionic fibers synapse directly on Chromaffin cells in the adrenal medulla. The Chromaffin cells secrete hormone into the circulation directly - Epinephrine – 80% - Norepinephrine – 20%

Storage of CATECHOLAMINES in CHROMAFFIN GRANULES ADRENAL MEDULLA Both epinephrine and Norepinephrine belong to chemical class of CATECHOLAMINES, which are derived from the amino acid TYROSINE. Storage of CATECHOLAMINES in CHROMAFFIN GRANULES Epinephrine and Norepinephrine are synthesized in the cytosol of adrenal medulla secretary cells and stored in Chromaffin granules.

SECRETION OF CATECHOLAMINES FROM THE MEDULLA Epinephrine and Norepinephrine are secreted by exocytosis. Main effect of adrenal medulla is due to epinephrine [which is released 80%]. NOTE – In sympathetic ANS, postganglionic sympathetic nerve endings release Norepinephrine which has main action on the Effector organ.

Epinephrine and Norepinephrine Effect On Adrenergic Receptors Adrenergic Receptors are α1, α2, β1, and β2. Epinephrine has effect on alpha and beta. more effect on β2 , therefore, more effective in bronchial asthma and skeletal muscle [where β2 receptors are present].

Epinephrine and Norepinephrine Effect On Adrenergic Receptors Norepinephrine has effect alpha and beta, more effect on β1. NOTE – Epinephrine discharge from adrenal medulla always accompanies generalized sympathetic nervous system discharge.

Epinephrine and Norepinephrine Effect On Adrenergic Receptors RECEPTOR TYPE NEUROTRANSMITTER AFFINITY α1 Norepinephrine > Epinephrine α2 β1 Norepinephrine = Epinephrine β2 Epinephrine

ADRENAL MEDULLA Adrenomedullary hormones are not essential for life, but they are very important and work in stress response, regulation of blood pressure and have metabolic effects. Sympathetic ANS and epinephrine work for fight or flight response that is to combat enemy or flee from danger.

METABOLIC EFFECTS OF EPINEPRINE Effect on Carbohydrate - Epinephrine mobilizes stored carbohydrates to provide energy for use of muscular work. - Epinephrine increases blood glucose level by stimulating both hepatic [liver] Gluconeogenesis and glycogenolysis. Epinephrine also stimulates glycogenolysis in skeletal muscle.

METABOLIC EFFECTS OF EPINEPRINE Epinephrine increases blood glucose by inhibiting the secretion of insulin and stimulating glucagon. Epinephrine causes lipolysis, therefore, increase blood fatty acids. Therefore, epinephrine metabolic effect are appropriate for fight or flight reaction.

OTHER EFFECTS OF EPINEPHRINE Epinephrine affects CNS alertness – it allows quick thinking, therefore, helps in emergency situations. CNS stimulant or sedative drugs – work by increasing or decreasing catecholamine in CNS. Both Epinephrine and Norepinephrine cause sweating. Epinephrine dilates pupil.

CONTROL OF EPINEPHRINE RELEASED BY ADRENAL MEDULLA Catecholamine secretion from adrenal medulla is controlled by sympathetic input to adrenal medulla by preganglionic fibers coming from thoracic T5-T9 and T10-T11. Preganglionic fibers release acetylcholine. Adrenal medulla release Epinephrine and Norepinephrine into the circulation directly.

STRESS RESPONSE

STRESS RESPONSE Both components of adrenal glands i.e. Cortisol from adrenal cortex and catecholamine from adrenal medulla play important role in stress.

STRESS RESPONSE Stress can be induced by 1. Physical Stress – trauma, surgery, intense heat or cold 2. Chemical Stress – Hypoxia, acid-base balance disturbances 3. Physiological Stress – heavy exercise, pain 4. Pathological Stress – Hemorrhagic shock, infections 5. Psychological Stress – anxiety, fear, sorrow 6. Social Stress – change in life style, conflicts

STRESS RESPONSE Stress response is generalized reaction to any situation that affects homeostasis.

STRESS RESPONSE These responses [specific and non-specific] are called General adaptation syndrome. When there is a stress, body responds by nervous and hormonal responses, therefore, there is 1. Intense readiness 2. Mobilization of biochemical resources

ROLE OF SYMPATHETIC AUTONOMIC NERVOUS SYSTEM [ANS] & EPINEPRINE IN STRESS Sympathetic ANS causes fight or flight response. There is increased cardiac output. Increased ventilation. Increased blood supply to skeletal muscle. Epinephrine from adrenal medulla causes mobilization of carbohydrate and fat, therefore, increases blood glucose and fatty acids.

ROLE OF CRH – ACTH – CORTISOL SYSTEM IN STRESS Cortisol causes 1. Increased blood glucose level 2. Increased blood amino acids 3. Increased fatty acids Glucose provides nourishment to the brain.

ROLE OF OTHER HORMONAL RESPONSES IN STRESS There is decreased insulin and increased glucagon due to sympathetic ANS stimulation and epinephrine. Increased Renin angiotensin aldosterone [which maintains blood volume and blood pressure]. Increased vasopressin activity.

STRESS RESPONSE Stress response is coordinated by the hypothalamus. Hypothalamus gets input from brain and many receptors throughout the body. In response, hypothalamus directly activates sympathetic ANS, secretes CRH to stimulate ACTH and Cortisol release. It also triggers the release of vasopressin.

STRESS RESPONSE Sympathetic stimulation brings secretion of epinephrine, therefore, there is decreased insulin secretion and increased glucagon. Increased Renin angiotensin aldosterone response.

ACTIVATION OF STRESS RESPONSE BY CHRONIC PSYCHOSOCIAL STRESS Psychosocial Stress maybe harmful like - anxiety about examination - anxiety home affairs In these situations, no extra energy is demanded as no tissue is damaged but body stores are broken down needlessly.

ACTIVATION OF STRESS RESPONSE BY CHRONIC PSYCHOSOCIAL STRESS There is a strong evidence that there is a link between chronic exposure to psychosocial stressors and the development of high blood pressure due to sympathetic vasoconstriction, salt and water retention due to too much vasopressin and Renin-angiotensin- aldosterone effects.

PHAEOCHROMOCYTOMA It is rare tumor of adrenal medulla [Chromaffin cells] and secrete increased amount of catecholamine, epinephrine and Norepinephrine. Pheochromocytoma causes - increased heart rate - hypertension – intermittent or constant - increased blood glucose

PHAEOCHROMOCYTOMA Diagnosis - plasma catecholamine - urinary metabolites VMA [vanillyl mandelic acid] - CT scan - MRI - Treatment - Surgical Resection When operation is not possible then combined alpha and beta blockage can be used long term.

WHAT YOU SHOULD KNOW FROM THIS LECTURE? Adrenal Medulla Release of Hormones from Adrenal Medulla Effect of Catecholamine on Adrenergic Receptors Metabolic Effects of Epinephrine Control of Catecholamine released from Adrenal Medulla Types of Stress Stress Response by body Role of Hypothalamus in Stress Response PHAEOCHROMOCYTOMA

THANK YOU