Monday, May 1, 2023

ADRENAL GLAND(Glucocorticoids)

DR.NILESH KATE. M.D.

ASSOCIATE PROFESSOR,DEPARTMENT OF PHYSIOLOGY.

OBJECTIVES Physiological actions Pharmacological actions Effect of stress – General adaptation

syndrome Applied aspects –

Cushing’s syndrome Addison's disease.

PHYSIOLOGICAL ACTIONS Metabolic effect.

On carbohydrate metabolism. On fat metabolism On protein metabolism Electrolyte & water metabolism

On various organ systems. Anti-inflammatory & anti-allergic effect.

Monday, May 1, 2023

METABOLIC EFFECT. Carbohydrate metabolism.– anti-insulin

effect leads to hyperglycemia. Basically provide fuel molecules in

circulation. To maintain overnight metabolic

stability. Increased gluconeogenesis Utilization of glucose in peripheral tissue.

Monday, May 1, 2023

ON FAT METABOLISM Lipolytic effect –

Permissive role in lipolysis.

Indirect stimulation of lipolysis.

Fatty acid synthesis inhibition by liver.

Lipogenic role.– redistribution of fats

Monday, May 1, 2023

ON PROTEIN METABOLISM Catabolic effect.

Alanine pyruvic acidglucose

formation

Anti -Anabolic effect. (except liver)

Monday, May 1, 2023

Electrolyte & water metabolism Retention of sodium & water.

Mineralocorticoids activity. Aldosterone secretion.

Promotion of diuresis.(Inactivation of ADH & Antagonizing action on DCT)

Adrenal cortex insufficiency Water intoxication.

Monday, May 1, 2023

Permissive action Small amount of Glucocorticoids must

be present for Glucagon & catecholamine's – for

caloregenic action. Catecholamine's – for Lipolytic &

glycogenolytic action. For pressor response & bronchodilatation.

Monday, May 1, 2023

Effect on muscles. Contractility & work performance.

Skeletal -- ach synthesis at N-M Junction Cardiac – Na-K ATPase & β adrenergic

receptors. Decreased in muscle mass & strength

(excess of cortisol). Weak & thin extremities.

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Effect on bones. bone resorption. osteoclastic activity. & collagenase

activity. Inhibition of bone formation.

Inhibiting osteoblastic activity. Apoptosis of osteoblast & osteocytes. Osteoporosis.

Monday, May 1, 2023

Effect on connective tissue. collagen synthesis.

Thinning of skin.

Thinning of capillaries.

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Effect on vascular system. Sustain myocardial performance. Vaso-pressure effect. –

enhancing catecholamine & angiotensin II Decrease vasodilator PG.

Monday, May 1, 2023

Effect on kidney. G.F.R.

Calcium & phosphate excretion.

excretion of water load.

Monday, May 1, 2023

ON STRESS Stress is defined as an undue

response to strain which may be physical, mental, internal or external

General Adaptation SyndromeGeneral Adaptation Syndrome

Monday, May 1, 2023

STRESSSTRESSPhysical

EmotionsHypoglycaemia

Tissue actions

C.R.H.C.R.H. CIRCADIANRHYTHM

Neg

ativ

e fe

edba

ck

Glucocorticoids

(-)

(-)

(+)

A.C.T.H.A.C.T.H.(+)

Î Î Heart rateÎ Force of contractionÎ Blood sugarÎ Permissive action

Central nervous sytem. GR- Receptors mainly in limbic system. In Addison’s disease.( decreased levels)

Mood changes – irritability. Inability to concentrate.

Increased sensitivity to olfactory & gustatory stimuli.

In cortisol excess. Increased brain excitability Decreased threshold – convulsions.

Monday, May 1, 2023

G.I.T gastric acid

secretions.

proliferation of gastric mucosal cells.

Peptic ulceration.

Monday, May 1, 2023

BLOOD CELLS & LYMPHATIC ORGANS.

Polycythemia. – stimulate erythropoiesis.

Thrombocytosis. Neutrophilia.

Monday, May 1, 2023

BLOOD CELLS & LYMPHATIC ORGANS.

Eosinopenia & basopenia.

Lymphopenia.

Monday, May 1, 2023

Anti-inflammatory effect. local reactions tissue damage. fibroblastic activity. endogenous

pyrogens.

Antiallergic & anti-immunity effect.

Monday, May 1, 2023

PHARMACOLOGICAL ACTIONS

Other actions Maturation of CNS, Retina & skin. Maturation of lungs.

Phosphatidyl acid phosphatase. Choline phosphotransferase. Surfactant.

Maturation of GIT.

Monday, May 1, 2023

APPLIED ASPECTS. Secretions -- Cushing’s syndrome.

(hypercortisol state.)

Secretions – Addison’s disease.( hypocortisol

state.)

Monday, May 1, 2023

Cushing’s syndrome. Group of clinical

conditions – due to prolonged excessive levels of Glucocorticoids.

Monday, May 1, 2023

ACTH dependent Cushing's disease Ectopic ACTH syndrome Ectopic corticotropin- releasing hormone syndrome

ACTH independent Iatrogenic Adrenal adenoma Micronodular hyperplasia Macronodular hyperplasia

24

Causes -- Classification

Characteristic features. ( Harvey Cushing)

carbohydrate metabolism.carbohydrate metabolism. steroid (adrenal) diabetes.steroid (adrenal) diabetes.Hyperlipidemia & ketosis.Hyperlipidemia & ketosis.Hyperglycemia Hyperglycemia Glycosuria .Glycosuria .

Monday, May 1, 2023

FAT METABOLISM.

Monday, May 1, 2023

Centripetal distribution of fat

Thin extremities. This case described

by Cushing in 1912.

Fat metabolism.(cont….) Deposition of fat. (lemon on

toothpick)

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Pendular abdomen.Reddish purple striaeFace (moon like)

Abdominal striae.

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Pendular abdomenRupture of thin skin due to stretching.

Buffalo hump (upper back)

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Fish mouth

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Before treatment After treatment. Hirsutism

Protein metabolism. Negative nitrogen balance Steroid myopathy. Skin- thin & paper like Poor wound healing Hair – thin & rough, loss of scalp hair. Thin extremities – muscle wasting.

Monday, May 1, 2023

Other symptoms

Monday, May 1, 2023

Water & electrolyte metabolismoedema & hypertension.

Bone – osteoporosisBlood – Polycythemia

Thrombocytosis Eosinopenia Basopenia Lymphopenia.

CNS – Psychosis, restlessness excitability.

Sexual changes -- Amenorrhea

TESTS FOR CUSHING’S SYNDROME

Plasma cortisol levels Dexamethasone suppression test. Insulin induced hypoglycemia. 24 hr urinary free cortisol. To distinguish between ACTH

DEPENDENT & ACTH INDEPENDENT. Metyrapone test.- levels of 11-deoxycortisol

after 24 hr administration of metyrapone.

Monday, May 1, 2023

Addison’s disease Adrenal insufficiency is known as

Addison’s disease. Causesa) Auto--immune disease.b) Destruction of adrenal gland due to

cancer or Tuberculosis.c) Bilateral adrenalectomy.d) Malignant tumors.

Monday, May 1, 2023

ADDISON’S DISEASES (THOMAS ADDISON -

1855) 1 Muscular weakness 2. Hypoglycemia 3. Hypotension 4. Anaemia 5. Hypo volemia and Haemo concentration 6. Resistance to stress and infection is less 7. Disturbed electrolyte balance 8. Persons suffer from anorexia, nausea, vomiting and

weight loss. 9. Addisonian crisis.

Monday, May 1, 2023

Pigmentation of skin.

Monday, May 1, 2023

Increased ACTH secretion for long time

β- MSH activity.

Generalised pigmentation of skin (melanin deposition)

Pigmentation of skin.

Monday, May 1, 2023

Pigmentation of palm & face, cheek, tongue, gums & ear.

Addisonian Crisis”

Monday, May 1, 2023

Stress precipitates a collapse.

Causes.—After adrenalectomy.After abrupt withdrawal of therapeutically administered Glucocorticoids. Treatment Mineralocorticoids & Glucocorticoids administration daily

OBJECTIVES Physiological actions Pharmacological actions Effect of stress – General adaptation

syndrome. Applied aspects –

Cushing’s syndrome. Addison's disease.

Thank you THANK YOU