Adrenal Medulla Physiology Notes

Adrenal Medulla Introduction

Medulla is the inner part of the adrenal gland and it forms 20% of mass of adrenal gland. It is made up of interlacing cords of cells known as chromaffin cells, photochrom cells, or chromophil cells. These cells contain fine granules which are stained brown by potassium dichromate. The chromaffin cells are of two types:

1. Adrenaline-secreting cells (90%)
2. Noradrenaline secreting cells (10%).

Read And Learn More: Medical Physiology Notes

Hormones Of Adrenal Medulla

Adrenal medullary hormones are the amines derived from catechol and so these hormones are called catecholamines. Three catecholamines are secreted by medulla:

1. Adrenaline or epinephrine
2. Noradrenaline or norepinephrine
3. Dopamine.

Plasma Level Of Catecholamines

1. Adrenaline : 3 pg/dL
2. Noradrenaline : 30 pg/dL
3. Dopamine : 3-5 Mg/dL

Half-Life Of Catecholamines: The 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. 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
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. The biological inactivation (degradation) and removal of the remaining 15% of noradrenaline and adrenaline occur 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, the oxidation of metanephrines into vanillylmandelic acid (VMA) occurs by monoamine oxidase (MAO)
3. Catecholamines are removed from body through urine in three forms:
   1. 15% as free adrenaline and free noradrenaline
   2. 50% as free or conjugated meta-adrenaline and meta noradrenaline
   3. 35% as 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 the cardiovascular system.

Mode Of Action Of Adrenaline And Noradrenaline – Adrenergic Receptors

The actions of adrenaline and noradrenaline are executed by binding with receptors called adrenergic receptors which are present in the target organs. Adrenergic receptors are of two types:

1. Alpha-adrenergic receptors
2. Beta-adrenergic receptors.

Alpha receptors are subdivided into alpha₁ and alpha₂ receptors, beta receptors are divided into beta₁ and beta₂ receptors.

1. Alpha Adrenergic Receptors: Alpha-adrenergic receptors mediate more of noradrenaline actions than adrenaline actions.
   1. Alpha₁ receptors: Alpha₁ receptors exert their actions by activating the second messenger inositol triphosphate (IP₃) through phospholipase C.
   2. Alpha₂ receptors: Alpha₂ receptors exert their effects by inhibiting adenyl cyclase and reducing intracellular cyclic AMP.
2. Beta-Adrenergic Receptors
   1. Beta₁ receptors: Beta₁ receptors mediate the actions of both adrenaline and noradrenaline almost equally.
   2. Beta₂ receptors: Beta₂ receptors are larger than beta, receptors and mediate more of adrenaline actions than noradrenaline actions.

Both beta₁ and beta₂ receptors produce their actions by activating adenyl cyclase through G proteins and increasing intracellular cyclic AMP.

Actions

• The circulating adrenaline and noradrenaline show the same effect as that 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.
• The 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.
   1. General metabolism: Adrenaline increases oxygen consumption and carbon dioxide removal. It increases basal metabolic rate. So, it is said to be a calorigenic hormone
   2. Carbohydrate metabolism: Adrenaline increases the blood glucose level. It is by increasing the glycogenolysis in liver and muscle. So, a large quantity of glucose enters the circulation
   3. Fat metabolism: Adrenaline causes the 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 the spleen into circulation.
3. On Heart (via Beta Receptors): Adrenaline has stronger effects on heart than noradrenaline. It increases the overall activity of the heart, i.e.
   1. Heart rate (chronotropic effect)
   2. Force of contraction (inotropic effect)
   3. Excitability of heart muscle (bathmotropic effect)
   4. Conductivity in heart muscle (dromotropic effect).
4. On Blood Vessels (via Alpha and Beta₂ 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’. The vasoconstrictor effect of noradrenaline 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 beta₂ receptors. So, the total peripheral resistance is decreased by adrenaline.
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 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. Thus, hypersecretion of catecholamines leads to hypertension.
6. On Respiration (via Beta₂ 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 Beta₂ Receptors): Adrenaline causes contraction of arrector pili. It also increases the secretion of sweat.
8. On Skeletal Muscle (via Alpha and Beta₂ 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:
   1. Splenic capsule
   2. Sphincters of Gl tract
   3. Arrector pili of skin
   4. Gallbladder
   5. Uterus
   6. Dilator pupillae of iris
   7. Nictitating membrane of cat.
      • Catecholamines cause relaxation of smooth muscles in some organs like:
        1. Nonsphincteric part of Gl tract (esophagus, stomach, and intestine)
        2. Bronchioles
        3. 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
    1. On salivary glands (via alpha and beta₂ receptors) — cause vasoconstriction in salivary gland leading to mild increase in salivary secretion
    2. On sweat glands (via beta₂ receptors) – increase the secretion of apocrine sweat glands
    3. On lacrimal glands (via alpha receptors) – increase the secretion of tears
    4. On ACTH secretion (via alpha receptors) – adrenaline increases ACTH secretion
    5. On nerve fibers (via alpha receptors) – adrenaline decreases the latency of action potential in the nerve fibers, i.e. electrical activity is accelerated
    6. On renin secretion (via beta receptors) – increase the secretion of renin from the 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 also increases in:

1. Exposure to cold: During exposure to cold, adrenaline, and noradrenaline are secreted in large quantities. The catecholamines significantly increase 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 the adrenal medulla. The type of cells secreting this hormone is not known. Dopamine is also secreted by dopaminergic neurons in some areas of the brain particularly, the basal ganglia. In the brain, this hormone acts as a neurotransmitter. The 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 a nervous disorder called Parkinsonism.

Applied Physiology Pheochromocytoma

Pheochromocytoma is a condition characterized by hypersecretion of catecholamines.

• Applied Physiology Pheochromocytoma Cause: Pheochromocytoma is caused by a tumor of chromophil cells in the adrenal medulla. It is also caused rarely by tumors of the sympathetic ganglia (extra-adrenal pheochromocytoma).
• Applied Physiology 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. 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: It is detected by measuring metanephrines and vanillyl-mandelic acid in urine and catecholamines in plasma.