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Anatomy
• There are 2 adrenal glands each weighing about 4 gms
• They lie at the superor poles of the two kidneys
• Each gland is composed of two distinct parts adrenal cortex and adrenal medulla
• Blood supplied by superior ,inferior and middle adrenal arteries
Adrenal cortex
Three distinct layers-• Zona glomerulosa- thin layer under the capsule 15% of
the cortex. The cells here capable of secreting significant amount of aldosterone
• Zona fasiculata- middle widest layer 75%of cortex secreting glucocorticoids, cortisol and corticosterone as well as small amount of adrenal androgens and estrogen
• Zona reticularis- deep layer secretes adrenal androgens dehydroepiandrosterone(DHEA) and androstenedione as well as small amount of estrogen and glucocorticoid
Adrenal medulla
• It occupies the central 20 % of the adrenal gland
• It secretes the hormones epinephrine and nor epinephrine in response to sympathetic stimulation they are referred to as catecholamines
Biosynthesis of adrenal steroids
• Important steroid products of adrenal cortex are aldosterone , cortisol and androgens
• All the steps of syntheis occurs in mitochondria and endoplasmic reticulum
• Approx 90-95% of cortisol in plasma binds to plasma protein globulin called transcortin and to albumin
• Binding serves as a reservoir to lessen rapid fluctuations in free hormone concentration
• Adrenal steroids are degraded mainly by liver and conjugated to glucoronic acid or sulphates
• 25% of these conjugates are excreted in the bile and then in feces and remaining in urine
Mineralocorticoid- aldosterone
• Aldosterone is the principal mineralocorticoid secreted by the adrenal glands
• Aldosterone exerts 90% of the mineralocorticoid activity of adrenal cortex rest 10 % is by cortisol
• Aldosterone increases the reabsorption of sodium ions in the ECF
• It acts on principal cells of collecting ducts in the kidney increasing sodium in exchange of potassium and hydrogen ions
Renin angiotensin aldosterone system (RAAS)
• Aldosteone secretion is mainly controlled by angiotensin and potassium acting directly on adrenocortical cells
Factors that play a role in regulation of aldosterone
• Increased potassium ion concentration in the extracellular fluid
• Increased angiotensin II concentration in ECF• Increased sodium ion concentation in ECF• ACTH from anterior pituitary
Primary aldosteronism (Conn’s syndrome)
• A small tumor of zona glomerulosa secrete large amount of aldosterone
• The important effects are hypokalemia, mild metabolic alkalosis, slight increase in extracellular fluid volume and blood volume
• There is sometimes muscle paralysis due to hypokalemia
• There is decreased renin concentration• Treatment include surgical removal of tumor or
treatment with antagonist of mineralocorticoid receptor with spironolactone
• activation of MR receptor can be antagonized with Spironolactone
• Amiloride is a drug that can block sodium reabsorption
• This is used in treatment of primary aldosteronism
Glucocorticoids
• 95% of glucocorticoid activity occurs from secretion of cortisol known as hydrocortisone
• Cortisol has effects on – Carbohydrate metabolism– Protein metabolism– Fat metabolism– Antiinfammatory effects
Regulation of cortisol secretion
• ACTH stimulates cortisol secretion– Secretion of cortisol is controlled entirely by ACTH
• ACTH activates by increase in cAMP– ACTH acts on adrenaocortical cells to activate
adeny cyclase– Long term activation can cause hypertrophy
• Inhibitory effect of cortisol– Cortisol sends negative feedback to hypothalamus
and pituitary to regulate cortisol levels
Different types of stress that increase cortisol release
• Trauma of any type• Infection• Intense heat or cold• Injection of norepinephrine• Surgery• Any debilitating disease
Effect of cortisol in preventing inflammation
• Cortisol stabilizes the lysosomal membrane• Cortisol decreases the permeability of the
capillaries preventing loss of plasma into tissues• Cortisol decreases migration of WBCs into
inflamed area and phagocytosis of damaged cells• Cortisol suppresses the immune system causing
lymphocyte reproduction to decrease• Cortisol attenuates fever as it reduces the release
of interleukin-1
Adrenal androgens
• Adrenal androgens mainly dehydroepisterone is continully secreted by adrenal cortex during fetal life
• Small amount of estrogen and progesterone are also secreted
• It is believed early devlopment of male sex organs result from adrenal androgens
• Alrenal androgens are also responsible for axillary and pubic hair in females
Hypoadrenalism (Addison’s disease)
• This is due to insufficient adrenocortical hormones
• Most common cause is primary atrophy or injury, tuberculous destruction of the gland or cancer
• Disturbances cause mineralocorticoid deficiency, Glucocorticoid deficiency and melanin pigmentation
Addison’s disease
• Mineralocorticoid deficiency– Results in loss of sodium ions, chloride ions and water to be lost
into urine– This results in hyponatremia,hypercalemia and mild acidosis– Plasma voliume falls, cardiac output and blood pressure
decreases and patient dies in shock• Glucocorticoid deficiency
– No proper synthesis of glucose, reduced mobilization of proteins and fats
• Melanin pigmentation– Melanin pigmentation of mucous membrane and skin– Melanin deposited in blothes in thin areas of the skin due to
increased sectretion of MSH
Hyperadrenalism- Cushing’s syndrome
Hypercorticolism can occur due to-• Adenomas of the anterior pitutary secreting increased
ACTH• Abnormal function of hypothalamus causing increased
CRH and thereby increased ACTH• Ectopic secretion of ACTH by a tumor somewhere else
in the body• Adenomas of the adrenal cortexWhen cushing’s syndrome is secondary to excess
secretion of ACTH by the anterior pituitary this is called Cushing’s disease
Adrenal medulla
• The medulla has chromaffin cells named for characteristic brown staining with chromic acid
• Approx. 20% noradrenaline and 80% adrenaline is secreted
• Medulla recieves input from sympathetic nervous system through preganglionic fibres
• They end directly on modified neuronal cells that secrete epinephrine and norepinephrine into blood stream
• These secretory cells are embryonically derived from nervous tissue
Factors controlling secretion of catecholamines
• Position of individual- standing increases norepinephrine
• Exercise• Hypoglycemia stronly stimulates epinephrine secretion• Cigarette smoking• Surgery – both epinephrine and norepinephrine
secretion• Ketoacidosis• Myocardial infarction• Anesthesia
Adrenergic receptors
• There are 2 types of adrenergic receptors alpha and beta receptors
• Beta receptors are type 1,2 and 3 while alpha are type 1 and 2
• Norepinephrine and epinephrine both of which are secreted into the blood have slightly different effects in exciting alpha and beta receptors
• Norepinephrine exites mainly alpha receptors but beta also to lesser extent epinephrine exites both
• Effect is determined by type of receptors in the organs
Alarm or stress response of symphathetic nervous system
• Increased arterial pressure• Increased blood flow to active muscles for motor
activity• Increased rate of cellular metabolism• Increased glucose concentation • Increased glycolysis in liver and muscles• Increased muscle strength• Increased mental activity• increased rate of blood coagulation
Pheochromocytoma
• Tumors arise from chromaffin cells that secrete catecholamines
• 90% tumors arise in adrenal medulla• They are rare and equal occurance in males
and females• If present in children it may be heriditary• Most common feature is hypertension