Adrenal modulla

ADRENAL MEDULLA

ADRENAL MEDULLARY HORMONES

Hormones secreted by adrenal medulla:• Adrenal hormones are released by two types of

chromaffin cells.• One type of cells secrete norepinephrine and

other type of cells secrete epinephrine.• These hormones are stored in the form of

chromaffin granules.• In human, 80% of chromaffin granules contain

epinephrine and 20% of granules contain norepinephrine.

• These two hormones also called catecholamine.

Control of secretion of ad. medullary hormones:• Ad. Medulla is innervated by preganglionic

sympathetic nerves emerging mainly from lower thoracic segments of ipsilateal intermediolateral grey column of the spinal cord.

• the main physiology stimulus for release of hormones is acetylcholine from preganglionic sympathetic nerve endings innervating the chromaffin cells.

• Acetylcholine depolarizes the chromaffin cells which results into ca++ influx and release of catecholomins into the blood by exocytosis.

• Gland is also activated in response to stress called the flight or flight reaction.

• The following factors also stimulate sympathetic nervous system and also adrenal medulla to release catecholamine;

fear, anxiety, pain, trauma, haemorrhage, fluid loss, asphyxia, hypoxia, severe hypoglycaemia.• During hypoglycaemia ad. gland stimulated

independently. Also anger state of anxiety stimulate the gland independently.

Metabolism of catecholamines:• The half-life of catecholamines after entering

the circulation is about 2 minutes.• 85% of noradrenaline is taken up by the

sympathetic adrenergic neurons.The biological inactivation (degradation) and removal of remaining 15% of noradrenaline and adrenaline occurs in the following manner.

1. Adrenaline is methoxylated into meta-adrenaline. Noradrenaline is methoxylated into meta-noradrenaline.The methoxylation occurs in the presence of ‘Catechol-O-Methyltransferase’ (COMT). Meta-adrenaline and meta – noradrenaline are together called metanephrines.2. Then, oxidation of metanephrines into vanillylmandelic acid (VMA) occurs by monoamine oxidase (MAO).

3. Catecholamines are removes from body through urine in three forms:i. 50% as free or conjugated meta – adrenaline

and meta – noradrenaline.ii. 35% as VMA.iii. Remaining 15% as free adrenaline and free

noradrenaline.

Adrenergic receptors:1. Alpha receptors; are activated by both

epinephrine and norepinephrine and are mostly associated with excitatory functions of the body.

2. Beta receptors; respond to mainly epinephrine and are associated mainly with inhibitory functions.

Physiological effects of catecholamine through alpha and beta receptors:Effects of catecholamine are the same as those of sympathetic stimulation except that effects are of longer duration and produced on the tissues which are not innervated by sympathetic nerves.

Effects of catecholamines through alpha receptors:

Effects of catacholamines through beta receptors:

Effects of catechol. on carbohydrate metabolism:• Metabolic effects of catechol. are mainly

through epinephrine. Norepinephrine has little effect.

1. Effect on liver;a) Glycogenolysis in liver – epinephrine increases glycogenolysis in liver via Ca2++ activated glycogen phosphorylase and inhibition of glycogen synthesis. This causes increase in blood glucose level.

b) Epinephrine also increases glucose production from lactate amino acid and glycerol which are glucogenic substances.2. Effect on muscles;Epinephrine stimulate glycogenolysis in muscles by beta adrenergic receptors mechanism involving stimulation of adenyl cyclase and cyclic AMP induced stimulation of glycogen phosphorylase.

3. Effects of epinephrine on fat metabolism;• Ep. Stimulates lipolysis by activating triglyceride

lipase via beta adrenergic receptors.• Also mobilizes free fatty acids stored in adipose

tissue supplying substrate for ketogenesis in liver.• Acetoacetate and beta hydroxybutyrate formed are

transported from liver to peripheral tissues and are utilized for energy purpose.

• Cardiac muscle (specially) uses FA and acetoacetate in preference to glucose for energy purpose.

• Resting skeletal muscle also uses fatty acids.

Difference in the action of epin. And norepi:• Epi. has a greater effect on cardiac stimulation

because of its greater effect in stimulating beta receptors.

• Epi. causes weaker constriction of blood vessels compared to strong vasoconstriction caused by norepi.

• Due to its strong vasoconstriction effect, norepi. is given in case of shock to increase BP.

• Epi. has 5 to 10 times greater metabolic effects as compared to metabolic effects of norepi.

• Epi. also increases the metabolic rate of the body as much as 100% above normal.

Regulation of secretion of adrenaline and noradrenaline:• Adrenaline and noradrenaline are secreted in

adrenal medulla in small quantities even during rest.

• During stress conditions, due to sympathoadrenal discharge, a large quantity of catecholamines is secreted.

• These hormones prepare the body for fight or flight reactions.

• Catecholamine secretion also increases in:1. Exposure to cold: During exposure to cold,

adrenaline and noradrenaline are secreted in large quantities. The catecholamines significantly increase the muscular activity and sometimes produce shivering so that, the body temperature increases.

2. Hypoglycemia: release of catecholamines increases during hypoglycemia. These hormones increase the blood sugar level by inducing glycogenolysis in muscle.

Dopamine:• Dopamine is secreted by adrenal medulla.• The type of cells secreting this hormone is not

known.• Dopamine is also secreted by dopaminergic

neurons in some areas of brain particularly, basal ganglia.

• In brain, this hormone acts as a neurotransmitter.

• The other physiological functions of circulating dopamine are not understood clearly.

• The injected dopamine produces the following effects:

1. Vasoconstriction by releasing nor- epinephrine.

2. Vasodilatation in mesentery.3. Increase in heart rate via beta receptors.4. Increase in systolic blood pressure. Dopamine

does not affect diastolic blood pressure.• Deficiency of dopamine in basal ganglia

produces nervous disorder called Parkinsonism.

Applied physiology pheochromocytoma:• Pheochromocytoma is a condition

characterized by hypersecretion of catecholamines.

Cause:• Pheochromocytoma is caused by tumor of

chromophil cells in adrenal medulla.• It is also caused rarely by tumor of

sympathetic ganglia (extra adrenal Pheochromocytoma).

Signs and symptoms:• The characteristic feature of

pheochromocytoma is hypertension.• This type of hypertension is known as

endocrine or secondary hypertension.• Other features are:1. Anxiety2. Chest pain3. Fever4. Head ache5. Hyperglycemia6. Metabolic disorders

7. Nausea and vomiting8. Palpitation9. Polyuria and glucosuria10. Sweating and flushing11. Tachycardia12. Weight lossTests for pheochromocytoma:• It is detected by measuring metanephrines

and vanillylmandelic acid in urine and catecholamines in plasma.

The end