ADRENAL GLAND

ADRENAL CORTEX ADRENAL MEDULLA

Goals for learningGoals for learning

Functional anatomy of adrenal glandHormones and their synthesisFunctions of the hormonesCellular mechanismRegulation of their secretionEffect of their altered secretion

Adrenal glandAdrenal gland Adrenal cortex

– Zona glomerulosa-Mineralocorticoid Aldosterone, Deoxycorticosterone

– Zona fasciculata-Glucocorticoids Cortisol, Corticosterone, Cortisone– Zona reticularis-Adrenal androgens Androsterone, DHEA sulphate Adrenal Medulla

Epinephrine Nor epinephrineDopamine

Cholesterol

Pregnenolone 17 OH Pregnenalone DHEA

Progesterone 17 OH Pregnenalone Andro

stenedione

11 Deoxy 11 DeoxycortisolCorticosterone Testosterone

Corticosterone Cortisol Estradiol

Glucocorticoids Glucocorticoids CortisolCorticosteroneCortisonePredinisolone (synthetic)Dexamethasone (synthetic)

Concentration of cortisol is 13.5 microgram/100 ml, Secretion 15-20mg/day

Transport Cortisol binding globulin(CBG)/ transcortin

GLUCOCORTICOIDSGLUCOCORTICOIDSCORTISOLCORTISOL

This is a C21 steroid produced mainly from zona fasciculata.

It combines with cortisol binding globulin. 96 % of the cortisol is transported in bound form.

Only 4 % is transported in free form.It stays in circulation for 1 to 2 hours.It is degraded in the liver and conjugated to form

glucuronides. It is excreted in urine.

MECHANISM OF ACTIONMECHANISM OF ACTION

These hormones enter the cell and combine with receptors in the cytoplasm. Hormone receptor complex induces portion of DNA to form m RNA.

The m RNA causes protein formation. These proteins are responsible for actions of glucocorticoids.

Onset of action is 45-60 min

FunctionsFunctionsMetabolism CHO, Proteins, Lipids, Mineral and WaterPermissive ActionEffect on ACTH secretionVascular permeabilityOn Nervous SystemOn Blood cells and Lymphatic organsResistance to StressAnti inflammatory and Antiallergic Effects

On carbohydrate metabolismOn carbohydrate metabolism It stimulates gluconeogenesis by the liver by

increasing glucose-6-phosphatase.

It decreases rate of glucose utilization by the peripheral tissues by inhibiting phosphorylation (anti-insulin action)

Increases glycogen synthesis in liver by increasing activity of glycogen synthase.

On protein metabolismOn protein metabolismIt causes protein breakdown in skeletal

muscles.Cortisol enhances amino acid uptake by the

liver cells & enhances transamination - (AA synthesis), deamination – (glucose formation)

Hence proteins like plasma proteins produced by liver are increased

On fat metabolismOn fat metabolism

It causes fatty acid mobilization from adipose tissue increasing free fatty acids in plasma.

It stimulates absorption of lipids from the intestine.

It causes redistribution of fats in the body.

Water and Mineral metabolismWater and Mineral metabolism

Mild mineralocorticoid activity – retains Na & excretes K

Increases angiotensinogen synthesis in liver leading to Na retention via aldosterone

Provides adequate GFR via anti-ADH activity

Permissive actionPermissive actionOn glucagon & catecholamines to exert

calorigenic actionOn catecholamines to exert lipolytic effect

& glycogenolytic effect.On catecholamines to exert pressor

response & bronchodilation.

In stress In stress Offers resistance to StressStress causes increase in ACTH secretion

followed by secretion of cortisolStress causes General Adaptation Syndrome in

2 phases: 1 Stage of Alarm 2 Stage of Resistance: in which cortisol

interacts with catecholamines – activation of sympatho-adrenal medullary system.

Effect on blood cellsEffect on blood cells

EosinopeniaLymphopeniaBasopenia Neutrophilia Polycythemia Platelet count

On BoneOn BoneIt causes demineralization of boneRetards development of cartilageThinning of epiphyseal plateBreaks down bone matrixDecreases calcium depositionIncreases calcium excretionDecreases calcium absorption from GITResults in osteoporosis and tetany

Anti inflammatory & Antiallergic Anti inflammatory & Antiallergic EffectEffect

Pharmacological dosesInhibits Phospholipase A2Reduces the release of arachidonic acid &

consequently reduces the formation of leukotriens, thromboxanes, prostaglandins and prostacyclins.

It reduces leucocyte margination, chemotaxis, phagocytosis of bacteria.

It prevents development of fibroblasts & delays wound healing

REGULATIONREGULATION

Cortisol secretion is controlled by ACTH. ACTH is secreted in irregular bursts

throughout the day. Plasma cortisol rises and falls in response to these bursts. Plasma cortisol is high in mornings (20mg/dl ) and very low (5mg/dl) in evenings.

Trauma Emotions Afferents Circadian rhythm from NTS CRH

cortisol ACTH Adrenal cortex

CUSHING’S SYNDROMECUSHING’S SYNDROMEExcess secretion of glucocorticoids.

Causes Adrenocortical tumours Anterior pituitary tumours Ectopic ACTH producing tumour Prolonged glucocorticoid therapy.

– Cushing’s syndrome caused due to tumours of anterior pituitary is called Cushing’s disease.

Signs & symptomsSigns & symptoms Fat collects in the abdominal

wall, face and upper back producing buffalo hump and moon face.

Skin and subcutaneous tissues are thin.

Muscles are poorly developed.

Wounds heal poorly, minor injuries cause bruises

Osteoporosis occur. There is insulin resistant

diabetes mellitus due to gluconeogenesis .

Signs & symptomsSigns & symptoms There is salt and water

retention, K+ depletion and weakness due to mineralocorticoid activity of cortisol .

Protein depletion occurs due to its excessive catabolism.

Hypertension develops due to increased deoxycorticosterone production.

Reddish purple striae appear in the skin due to rupture of subdermal tissues

TreatmentTreatmentRemoval of tumour in adrenal or pituitary

gland.If removal of pituitary tumour is not

possible, then removal of both adrenals with supplementation of steroids.

SummarySummary

Hormones of Adrenal CortexGlucocorticoids-Mechanism, FunctionsCushing’s Syndrome

Study questionsStudy questionsName the layers of adrenal cortex and list the

hormones secreted by themDescribe the functions of glucocorticoidsWhat is permissive action of a hormone. Give

suitable example?Discuss the anti-inflammatory functions of

glucocorticoidsExplain the cause and clinical features of

cushing’s syndrome