Adrenal Glands

ADRENAL GLANDS Adrenal glands are two conical pyramid shaped glands and are situated just above each kidney. Each adrenal has an outer layer called as Adrenal cortex and a central portion called as Adrenal medulla. Adrenal cortex is essential for life where as Adrenal medulla helps to combat against emergency situations. ADRENAL CORTEX DIVIDED INTO THREE ZONES Zona glomerulosa It is the outermost zone in which cells are arranged with their long axis parallel to the surface. It secretes mineralocorticoids. Zona fasciculate It is the intermediate zone in which cells are lying vertical to the surface. It secretes glucorticoids. Zona reticularis It is the inner zone and cells are arranged irregularly with blood spaces in between. It secretes sex steroids. GLUCORTICOID REGULATORY MECHANISMS 1. CRH Corticotrophin Releasing Hormone from the hypothalamus stimulates the secretion of ACTH Adrenocorticotrophic hormone from the anterior pituitary 2. ACTH stimulates the secretion of glucorticoids DIURNAL variation of ACTH secretion Maximum between 6.00 am 9.00 am Diurnal variation is Regulated by suprachiasmatic nuclei of hypothalamus HYPOTHALAMUS →→→ANT PITUITARY →→→ ADRENAL CORTEX→→→COTISOL CRH ACTH

Free Glucorticoids inhibits ACTH secretion by inhibiting secretion of CRH and ACTH Mechanism - Glucorticoids stimulate DNA dependent mRNA synthesis ACTIONS Carbohydrate metabolism DIABETOGENIC z Leads to increase blood glucose z Increase gluconeogenesis z Prevents peripheral utilization of glucose FAT METABOLISM LIPOLYTIC ACTION z Increase mobilization of fatty acids from adipose tissue to liver z Increase lipase activity Protein metabolism CATABOLIC ACTION Protein breakdown ELECTROLYTE BALANCE z z z

Increases retention of sodium due to mild mineralocorticoid action. Increases secretion of aldosterone leading to increased water and sodium reabsorption. Antagonises action of ADH on kidney.

PERMISSIVE ACTION Glucorticoids are very essential for metabolic reactions to occur Important for other hormones to exert their effect eg catecholamines to produce pressor response CNS Glucocorticoids in excess decrease excitability of neurons causing convulsions

GIT Increase gastric acid secretion therefore promoting peptic ulcer formation BLOOD VESSELS Glucorticoids are essential for normal vascular reactivity Sensitizes the arterioles to vasoconstriction action of catecholamines

ANTIINFLAMATORY ACTION Prevents tissue damage by stabilizing lysosomal membranes Decrease hyperemia, exudation, migration and infiltration of leucocytes at the site of injury Decrease hypersensitivity response to antigen – antibody reaction Decreases release of pyrogens from granulocytes. Lowers fever BLOOD CELLS Causes Neutrophilia Basopenia Eosinopenia Lymphopenia Polycythemia Clotting time is reduced APPLIED CUSHING’S SYNDORME EXCESS CIRCULATING LEVELS OF GLUCORTICOIDS CAUSES z ADRENAL TUMOURS SECRETING EXCESS GLUCORTICOIDS z ADRENAL HYPERPLASIA z EXCESS INTAKE OF GLUCORTICOIDS

CHARACTERISTIC FEATURES 1. PROTEIN CATABOLISM Wasting of muscles Growth retardation Thinning of skin and subcutaneous tissues Poor wound healing 2. CARBOHYDRATE METABLOISM Diabetogenic Cause hyperglycemia Increased resistance to insulin 3. FAT METABOLSM Redistribution of fat Centripetal distribution OF FAT Characterized by z z

Thin extremities Fat deposition over abdomen over face leads to MOON FACE upper back causing BUFFALO HUMP 4. PROMOTES ATHEROSCLEROSIS BY INCREASING FFA ,LIPIDS 5. HYPERTENSION BY ITS MINERALOCORTICOID ACTION, RETENTION OF SODIUM AND WATER 6. CNS : PSYCHOSIS ,EXCITABILITY, NERVOUSNESS 7. GIT : PEPTIC ULCER FORMATION 8. ANTIINFLAMATORY ACTION 9. OSTEOPOROSIS BY INCREASING BONE RESORPTION 10. BLOOD : Eosinopenia, neutrophilia, basopenia , polycythemia, increased clotting time.

ADRENAL MEDULLA Consist of two types of cells I. Epinephrine secreting cells 80% II. Nor epinephrine secreting cells 20% z z

They stimulate the force of contraction of heart and increase heart rate. Adrenaline causes dilation of blood vessels in skeletal muscle and also increases blood glucose level.

NOTE – Dopamine is also synthesised from the sympathetic ganglia. RELEASE OF CATECHOLAMINES Stimulation of pre-ganglionic splanchnic fibers ↓ release of Ach ↓ Stimulate medullary chromaffin cells ↓ Secretion of epinephrine and nor-epinephrine into the blood ACTION OF CATECHOLAMINES There exist two types of adrenergic receptors: α and β. They have different sensitivities for different catecholamines and produce different response. 1. The α adrenergic receptors are sensitive to both epinephrine and norepinephrine. 2. α receptors are of two types α1 and α2 LOCATION α1 receptor α2 receptor

-

Post synaptic membrane Presynaptic nerve terminals of cholinergic and adrenergic nerves

ACTION α1 receptor α2 receptor

-

Excitatory Inhibitory

3. β adrenergic receptors respond to epinephrine and very less to norepinephrine. ACTION Excitatory action on myocardium. Two types β1 and β2, located mostly on the postsynaptic membrane. LOCATION β1 receptor β2 receptor

- Cardiac muscle - Skeletal muscular blood vessels. GIT and bronchioles

ACTION β1 receptor β2 receptor

- Tachycardia and increase myocardial contractility - Relaxation of blood vessels

Epinephrine acts equally on both α and β receptors while norepinephrine acts on α receptors. HEART SA node AV node

β1,β2 β1,β2

Tachycardia Increase in conduction velocity

β1,β2 Atria β1,β2 Ventricles Blood vessels Skeletal muscle and coronaries Lungs Bronchial muscle Glands GIT Stomach and intestine Urinary bladder Detrusor muscle

Increase in conduction velocity and contractility Increase in contractility and conduction velocity

α1α2 β2

Constriction Dilation

β2 α1 β2 α1α2β2

Bronchodilatation Decreased secretion Increased secretion Decreased motility

β2 α1

Relaxation Contraction

Trigone and sphincter Ureter Skin Pilomotor muscle Sweat gland Uterus

α1

Increases

α1 α1

Pilorection localised sweating

Liver Skeletal muscle

α1 β2 α1 β2 α1β2 β2

Constriction Relaxation Constriction Relaxation for far vision Glycogenolysis Increase contractility and glycogenolysis

Pancreas

α2

Inhibition of insulin and glucagon secretion Stimulation of insulin and glucagon secretion Renin secretion

Eye

β2 Kidney

β1

APPLIED Phaeochromocytoma: Tumour of chromaffin tissues. Secrete large amounts of epinephrine and nor epinephrine. FEATURES 1. Paroxysmal or sustained hypertension 2. Headache, sweating severe palpitation, substernal pain, anxiety 3. Increased body temperature, hyperglycemia 4. Increase in urinary excretion of catecholamines, VMA and metanephrines.

ALDOSTERONE MECHANISM OF ACTION Stimulate DNA dependent mRNA synthesis. Aldosterone binds to specific cytoplasmic receptor and induces Aldosterone induced Protein synthesis (AIP) which is responsible for Na+ transport. Net effect is increased transport of Na+ from tubular lumen into interstitium and ultimately into blood stream.

ACTIONS 1. Conservation of sodium and excretion of potassium ALDOSTERONE cause- Retention of sodium from kidney.

Acts on PRINCIPAL CELLS of DCT and CT causing Na+ reabsorption in exchange for K+ and H+ which are then excreted in urine. Increases excretion of potassium from kidney. 1. Due to Na+ reabsorption, Aldosterone causes water retention leading to increased GFR and RPF. 3. EFFECT ON ACID BASE BALANCE Secretion of excess amount of Aldosterone causes hypokalemia which leads to increase in intracellular H+.This leads to secretion of H+ over K+ in DCT and results in Metabolic Alkalosis Lack of secretion of Aldosterone leads to increase in intracellular K+ and therefore metabolic acidosis.

ESCAPE PHENOMENON Excessive secretion of Aldosterone causes hypernatremia leading to increase ECFV. Then Na+ excretion is increased due to increased secretion of ANP.

REGULATION RENIN ANGIOTENSIN SYSTEM RENIN is released in circulation by decreased effective circulating blood volume Due to z Hypovolemia z Hyponatremia z Hypotension z Increased sympathetic activity. z Standing position z Secondary hyperaldosteronism in cases of CHF, cirrhosis and nephrosis

JGA ----Æ Renin Angiotensinogen --------Æ Angiotensin I --------Æ angiotensin –II -------Æangiotensin III -----------Æ adrenal cortex -------Æ Aldosterone secretion -------------Æ retention of Na+ ------Æ Inreased ECFV ------Æ increased RPF--------INHIBITION TO JGA

CONN’S SYNDROME (primary hyperaldosteronism ) Excessive secretion of Aldosterone from adrenal cortex is characterized by I. Increased plasma Aldosterone levels. II. Rise in plasma sodium level III. Decrease in plasma potassium level that causes Muscular weakness, tetany Metabolic alkalosis Prolonged hypokalemia can cause kidney damage IV. Hypertension due to sodium retention V. Renin is decreased Secondary hyperaldosteronism Extra adrenal factors. CHF cirrhosis and nephrosis Renin is increased ADDISON’S DISEASE (Primary Adrenocortical insufficiency) Reduced secretion of Aldosterone and glucorticoids due to destruction of adrenal cortex . CAUSES Autoimmune disorder Tuberculosis Malignancy Clinical features 1. Hypotension 2. Loss of weight, anorexia, diarrhea, dehydration 3. Muscular weakness, lethargic

4. Increased ACTH leading to pigmentation of skin , mucous membrane, gums , darkening of areolas 5. water intoxication MULTIPLE CHOICE QUESTIONS:

ALDOSTERONE: a) b) c) d)

1. All are action of aldosterone except: Retention of sodium. Excretion of potassium. Increased water retention. Retention of chlorides.

2. Regulation of aldosterone is due to : a) Renin Angiotensin system. b) Thyroid hormones. c) Glucorticoids. d) Growth hormones.

a) b) c) d)

3. Renin is released in circulation by all except: hypovolemia hyponatremia. Hypertension. On standing. 4. One of the following is not true: d) Angiotensinogen is not converted to angiotensin I. e) Angiotensin II gets converted to angiotensin I. f) Aldosterone cause retention of sodium. g) Angiotensin II gets converted to Angiotensin III.

5. All are true of primary hyper aldosteronism except: a) b) c) d)

Increase in plasma potassium levels. Increase in plasma sodium levels. Hypertension. There are aldosterone levels.

g) h) i) j)

6. In Addison's disease , one of the following is true: loss of weight. Constipation. Hypotension. Increased secretion of aldosterone.

ADRENAL GLANDS a) b) c) d)

1. In the adrenal medulla, 80% cells are epinephrine secreting. 80% cells are norepinephrine secreting type. 20 % cells are epinephrine secreting. 80% cells are both epinephrine and nor epinephrine secreting.

2. Mineralocorticoid is secreted by a) zona glomerulosa. b) Zona fasciculata. c) Zona reticulata. d) All of the above. 3. One of the following is true: a) b) c) d)

stimulation of beta receptors causes all except Tachycardia. Increase in conduction velocity at AV Node. Increase renin secretion in kidney.

1. action of glucocorticoids are a) b) c) d)

Increase blood glucose levels. Lipolytic action. Cause protein breakdown. All of the above.

1. One of the following is aggravated by glucocorticoids except peptic ulcer. 2. Diabetes mellitus. 3. Hypertension. 4. Hypothyroidism.

1. Cause of cushing's syndrome are all except adrenal tumour. 2. Adrenel hyperplaia. 3. Excess intake of glucocorticoids. 4. Adrenal atrophy. 7. Patient with cushing syndrome present with all features except a) b) c) d)

Poor wound healing. Hypertension. Moon face. Decreased blood glucose.