INTRODUCTION
Medulla is the inner part of adrenal gland and it forms 20% of the mass of adrenal gland. It is made up of interlacing cords of cells known as chromaffin cells. Chromaffin cells are also called pheochrome cells or chromophil cells. These cells contain fine granules which are stained brown by potassium dichromate.
Types of chromaffin cells
Adrenal medulla is formed by two types of chromaffin cells:
1. Adrenaline-secreting cells (90%)
2. Noradrenaline-secreting cells (10%).
HORMONES OF ADRENAL MEDULLA
Adrenal medullary hormones are the amines derived from catechol and so these hormones are called catecholamines.
Catecholamines secreted by adrenal medulla
1. Adrenaline or epinephrine
2. Noradrenaline or norepinephrine
3. Dopamine.
PLASMA LEVEL OF CATECHOLAMINES
1. Adrenaline : 3 μg/dL 2. Noradrenaline : 30 μg/dL 3. Dopamine : 3.5 μg/dL
HALF-LIFE OF CATECHOLAMINES Half-life of catecholamines is about 2 minutes.
SYNTHESIS OF CATECHOLAMINES
Catecholamines are synthesized from the amino acid tyrosine in the chromaffin cells of adrenal medulla (Fig. 71.1). These hormones are formed from phenylalanine also. But phenylalanine has to be converted into tyrosine.
Stages of Synthesis of Catecholamines
1. Formation of tyrosine from phenylalanine in the presence of enzyme phenylalanine hydroxylase
2. Uptake of tyrosine from blood into the chromaffin
cells of adrenal medulla by active transport
3. Conversion of tyrosine into dihydroxyphenylalanine (DOPA) by hydroxylation in the presence of tyrosine
hydroxylase
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FIGURE 71.1: Synthesis of catecholamines. DOPA = Di- hydroxyphenylalanine, PNMT = Phenylethanolamine-N- methyltransferase.
4. Decarboxylation of DOPA into dopamine by DOPA decarboxylase
5. Entry of dopamine into granules of chromaffin cells
6. Hydroxylation of dopamine into noradrenaline by
the enzyme dopamine beta-hydroxylase
7. Release of noradrenaline from granules into the
cytoplasm
8. Methylation of noradrenaline into adrenaline by the
most important enzyme called phenylethanolamine- N-methyltransferase (PNMT). PNMT is present in chromaffin cells.
METABOLISM OF CATECHOLAMINES
Eighty five percent of noradrenaline is taken up by the sympathetic adrenergic neurons. Remaining 15% of noradrenaline and adrenaline are degraded (Fig. 71.2).
FIGURE 71.2: Metabolism of catecholamines. COMT = Catechol-O-methyltransferase, MAO = Monoamine oxidase.
Stages of Metabolism of Catecholamines
1. Methoxylation of adrenaline into meta-adrenaline and noradrenaline into metanoradrenaline in the presence of ‘catechol-O-methyltransferase’ (COMT). Meta-adrenaline and meta-noradrenaline are together called metanephrines
2. Oxidation of metanephrines into vanillylmandelic acid (VMA) by monoamine oxidase (MAO)
Removal of Catecholamines
Catecholamines are removed from body through urine in three forms:
i. 15% as free adrenaline and free noradrenaline
ii. 50% as free or conjugated meta-adrenaline and
meta-noradrenaline
iii. 35% as vanillylmandelic acid (VMA).
ACTIONS OF ADRENALINE AND NORADRENALINE
Adrenaline and noradrenaline stimulate the nervous system. Adrenaline has significant effects on metabolic functions and both adrenaline and noradrenaline have significant effects on cardiovascular system.
MODE OF ACTION OF ADRENALINE AND NORADRENALINE – ADRENERGIC RECEPTORS
Actions of adrenaline and noradrenaline are executed by binding with receptors called adrenergic receptors, which are present in the target organs.
Chapter 71tAdrenal Medulla 441
Adrenergic receptors are of two types:
1. Alpha-adrenergic receptors, which are subdivided
into alpha-1 and alpha-2 receptors
2. Beta-adrenergic receptors, which are subdivided
into beta-1 and beta-2 receptors.
Refer Table 71.1 for the mode of action of these receptors.
ACTIONS
Circulating adrenaline and noradrenaline have similar effect of sympathetic stimulation. But, the effect of adrenal hormones is prolonged 10 times more than that of sympathetic stimulation. It is because of the slow inactivation, slow degradation and slow removal of these hormones.
Effects of adrenaline and noradrenaline on various target organs depend upon the type of receptors present in the cells of the organs. Adrenaline acts through both alpha and beta receptors equally. Noradrenaline acts mainly through alpha receptors and occasionally through beta receptors.
1. On Metabolism (via Alpha and Beta Receptors)
Adrenaline influences the metabolic functions more than noradrenaline.
i. General metabolism: Adrenaline increases oxygen consumption and carbon dioxide removal. It increases basal metabolic rate. So, it is said to be a calorigenic hormone
ii. Carbohydrate metabolism: Adrenaline increases the blood glucose level by increasing the glycogenolysis in liver and muscle. So, a large quantity of glucose enters the circulation
iii. Fat metabolism: Adrenaline causes mobilization of free fatty acids from adipose tissues. Catecholamines need the presence of glucocorticoids for this action.
2. On Blood (via Beta Receptors)
Adrenaline decreases blood coagulation time. It
increases RBC count in blood by contracting smooth
muscles of splenic capsule and releasing RBCs from spleen into circulation.
3. On Heart (via Beta Receptors)
Adrenaline has stronger effects on heart than nor- adrenaline. It increases overall activity of the heart, i.e.
i. Heart rate (chronotropic effect)
ii. Force of contraction (inotropic effect)
iii. Excitability of heart muscle (bathmotropic effect)
iv. Conductivity in heart muscle (dromotropic effect).
4. On Blood Vessels (via Alpha and Beta-2 Receptors)
Noradrenaline has strong effects on blood vessels. It causes constriction of blood vessels throughout the body via alpha receptors. So it is called ‘general vasoconstrictor’. Vasoconstrictor effect of noradrena- line increases total peripheral resistance.
Adrenaline also causes constriction of blood vessels. However, it causes dilatation of blood vessels in skeletal muscle, liver and heart through beta-2 receptors. So, the total peripheral resistance is decreased by adrenaline.
Catecholamines need the presence of glucocor- ticoids, for these vascular effects.
5. On Blood Pressure (via Alpha and Beta Receptors)
Adrenaline increases systolic blood pressure by increasing the force of contraction of the heart and cardiac output. But, it decreases diastolic blood pressure by reducing the total peripheral resistance. Noradrenaline increases diastolic pressure due to general vasoconstrictor effect by increasing the total peripheral resistance. It also increases the systolic blood pressure to a slight extent by its actions on heart. The action of catecholamines on blood pressure needs the presence of glucocorticoids.
TABLE 71.1: Adrenergic receptors
Receptor
Mode of action
Response
Alpha-1 receptor
Activates IP3 through phospholipase C
Mediates more of noradrenaline actions than adrenaline actions
Alpha-2 receptor
Inhibits adenyl cyclase and cAMP
Beta-1 receptor
Activates adenyl cyclase and cAMP
Mediates actions of adrenaline and noradrenaline equally
Beta-2 receptor
Activates adenyl cyclase and cAMP
Mediates more of adrenaline actions than noradrenaline actions
IP3 = Inositol triphosphate
442 Section 6tEndocrinology
Thus, hypersecretion of catecholamines leads to hypertension.
6. On Respiration (via Beta-2 Receptors)
Adrenaline increases rate and force of respiration. Adrenaline injection produces apnea, which is known as adrenaline apnea. It also causes bronchodilation.
7. On Skin (via Alpha and Beta-2 Receptors) Adrenaline causes contraction of arrector pili. It also
increases the secretion of sweat.
8. On Skeletal Muscle (via Alpha and Beta-2 Receptors)
Adrenaline causes severe contraction and quick fatigue of skeletal muscle. It increases glycogenolysis and release of glucose from muscle into blood. It also causes vasodilatation in skeletal muscles.
9. On Smooth Muscle (via Alpha and Beta Receptors)
Catecholamines cause contraction of smooth muscles in the following organs:
i. Splenic capsule
ii. Sphincters of gastrointestinal (GI) tract
iii. Arrector pili of skin iv. Gallbladder
v. Uterus
vi. Dilator pupillae of iris
vii. Nictitating membrane of cat.
Catecholamines cause relaxation of smooth
muscles in the following organs:
i. Non-sphincteric part of GI tract (esophagus,
stomach and intestine)
ii. Bronchioles
iii. Urinary bladder.
10. On Central Nervous System (via Beta Receptors)
Adrenaline increases the activity of brain. Adrenaline secretion increases during ‘fight or flight reactions’ after exposure to stress. It enhances the cortical arousal and other facilitatory functions of central nervous system.
11. Other Effects of Catecholamines
i. On salivary glands (via alpha and beta-2 receptors): Cause vasoconstriction in salivary gland, leading to mild increase in salivary secretion
ii. On sweat glands (via beta-2 receptors): Increase the secretion of apocrine sweat glands
iii. On lacrimal glands (via alpha receptors): Increase the secretion of tears
iv. On ACTH secretion (via alpha receptors): Adrenaline increases ACTH secretion
v. On nerve fibers (via alpha receptors): Adrenaline decreases the latency of action potential in the nerve fibers, i.e. electrical activity is accelerated
vi. On renin secretion (via beta receptors): Increase the rennin secretion from juxtaglomerular apparatus of the kidney.
REGULATION OF SECRETION
OF ADRENALINE AND NORADRENALINE
Adrenaline and noradrenaline are secreted from 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 increases during exposure to cold and hypoglycemia also.
DOPAMINE
Dopamine is secreted by adrenal medulla. 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.
Injected dopamine produces the following effects:
1. Vasoconstriction by releasing norepinephrine
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 (Chapter 151).
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).
Chapter 71tAdrenal Medulla 443
Signs and Symptoms
Characteristic feature of pheochromocytoma is hyper- tension. This type of hypertension is known as endocrine or secondary hypertension.
Other features:
1. Anxiety
2. Chest pain
3. Fever
4. Headache
5. Hyperglycemia
6. Metabolic disorders
7. Nausea and vomiting 8. Palpitation
9. Polyuria and glucosuria
10. Sweating and flushing 11. Tachycardia
12. Weight loss.
Tests for Pheochromocytoma
Pheochromocytoma is detected by measuring meta- nephrines and vanillylmandelic acid in urine and Cathecolamines in olasma
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