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Adrenal Medulla
DANISH HASSAN
LECTURER, UNIVERSITY OF SARGODHA
Introduction
 Medulla, the inner part of adrenal gland
 20% of the mass of adrenal gland.
 Made up of interlacing cords of cells known as
chromaffin cells / pheochrome cells / chromophil
cells
 Contain fine granules
 Adrenal medulla is formed by two types of
chromaffin cells:
 Adrenaline-secreting cells (90%)
 Noradrenaline-secreting cells (10%)
 Hormones Of Adrenal Medulla
 They are the amines derived from catechol
 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
 Adrenaline : 3 μg/dL
 Noradrenaline : 30 μg/dL
 Dopamine : 3.5 μg/dL
„
 Half-life Of Catecholamines
 Half-life of catecholamines is about 2 minutes.
 Synthesis Of Catecholamines
 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
 85% of nor-adrenaline is taken up by the
sympathetic adrenergic neurons.
 Remaining 15% of noradrenaline and adrenaline
are degraded.
 Stages of Metabolism of Catecholamines
 Methoxylation of adrenaline into meta-adrenaline
 Methoxylation of noradrenaline into
metanoradrenaline in the presence of catechol-O-
methyltransferase (COMT).
 Meta-adrenaline and meta-noradrenaline are
together called metanephrines
 Oxidation of metanephrines into vanillylmandelic
acid (VMA) by monoamine oxidase (MAO)
 Removal of Catecholamines
 Catecholamines are removed from body through
urine in three forms:
 15% as free adrenaline and free nor-adrenaline
 50% as free or conjugated meta-adrenaline and
meta-noradrenaline
 35% as vanillylmandelic acid (VMA)
 Actions Of Adrenaline And Noradrenaline
 Adrenaline and noradrenaline stimulate the nervous
system.
 Adrenaline has significant effects on metabolic
functions
 Both adrenaline and nor-adrenaline have
significant effects on cardiovascular system
 Mode Of Action Of Adrenaline & Noradrenaline –
Adrenergic Receptors
 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:
 Alpha-adrenergic receptors, which are subdivided
into alpha-1 and alpha-2 receptors
 Beta-adrenergic receptors, which are subdivided into
beta-1 and beta-2 receptors.
 Actions
 Circulating adrenaline and noradrenaline have
similar effect of sympathetic stimulation.
 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.
 Nor-adrenaline 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 called calorigenic
hormone
2. 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
3. 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
noradrenaline.
 It increases 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 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 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 beta-2
receptors.
 So, the total peripheral resistance is decreased by
adrenaline.
 Catecholamines need the presence of gluco
corticoids, 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.
 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:
1. Splenic capsule
2. Sphincters of gastrointestinal (GI) 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 the following organs:
1. Non-sphincteric part of GI 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 beta-2
receptors):
 Cause vasoconstriction in salivary gland, leading to
mild increase in salivary secretion
2. On sweat glands (via beta-2 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 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 sympatho-adrenal
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
 Secreted by adrenal medulla.
 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 but does not affect
diastolic blood pressure.
Adrenal medulla

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Adrenal medulla

  • 2. Introduction  Medulla, the inner part of adrenal gland  20% of the mass of adrenal gland.  Made up of interlacing cords of cells known as chromaffin cells / pheochrome cells / chromophil cells  Contain fine granules
  • 3.  Adrenal medulla is formed by two types of chromaffin cells:  Adrenaline-secreting cells (90%)  Noradrenaline-secreting cells (10%)
  • 4.
  • 5.  Hormones Of Adrenal Medulla  They are the amines derived from catechol  So these hormones are called catecholamines.  Catecholamines secreted by adrenal medulla 1. Adrenaline or epinephrine 2. Noradrenaline or norepinephrine 3. Dopamine.
  • 6.  Plasma Level Of Catecholamines  Adrenaline : 3 μg/dL  Noradrenaline : 30 μg/dL  Dopamine : 3.5 μg/dL „  Half-life Of Catecholamines  Half-life of catecholamines is about 2 minutes.
  • 7.  Synthesis Of Catecholamines  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
  • 8.  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
  • 9. 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.
  • 10.
  • 11.  Metabolism Of Catecholamines  85% of nor-adrenaline is taken up by the sympathetic adrenergic neurons.  Remaining 15% of noradrenaline and adrenaline are degraded.
  • 12.
  • 13.
  • 14.
  • 15.  Stages of Metabolism of Catecholamines  Methoxylation of adrenaline into meta-adrenaline  Methoxylation of noradrenaline into metanoradrenaline in the presence of catechol-O- methyltransferase (COMT).  Meta-adrenaline and meta-noradrenaline are together called metanephrines  Oxidation of metanephrines into vanillylmandelic acid (VMA) by monoamine oxidase (MAO)
  • 16.
  • 17.  Removal of Catecholamines  Catecholamines are removed from body through urine in three forms:  15% as free adrenaline and free nor-adrenaline  50% as free or conjugated meta-adrenaline and meta-noradrenaline  35% as vanillylmandelic acid (VMA)
  • 18.  Actions Of Adrenaline And Noradrenaline  Adrenaline and noradrenaline stimulate the nervous system.  Adrenaline has significant effects on metabolic functions  Both adrenaline and nor-adrenaline have significant effects on cardiovascular system
  • 19.  Mode Of Action Of Adrenaline & Noradrenaline – Adrenergic Receptors  Actions of adrenaline and noradrenaline are executed by binding with receptors called adrenergic receptors, which are present in the target organs
  • 20.  Adrenergic receptors are of two types:  Alpha-adrenergic receptors, which are subdivided into alpha-1 and alpha-2 receptors  Beta-adrenergic receptors, which are subdivided into beta-1 and beta-2 receptors.
  • 21.  Actions  Circulating adrenaline and noradrenaline have similar effect of sympathetic stimulation.  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.
  • 22.  Adrenaline acts through both alpha and beta receptors equally.  Nor-adrenaline acts mainly through alpha receptors and occasionally through beta receptors
  • 23. 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 called calorigenic hormone
  • 24. 2. 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
  • 25. 3. Fat Metabolism:  Adrenaline causes mobilization of free fatty acids from adipose tissues.  Catecholamines need the presence of glucocorticoids for this action
  • 26. 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
  • 27. 3. On Heart (via Beta Receptors)  Adrenaline has stronger effects on heart than noradrenaline.  It increases 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)
  • 28. 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 noradrenaline increases total peripheral resistance.  Adrenaline also causes constriction of blood vessels.
  • 29.  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 gluco corticoids, for these vascular effects
  • 30. 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.
  • 31.  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
  • 32. 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.
  • 33. 7. On Skin (via Alpha and Beta-2 Receptors)  Adrenaline causes contraction of arrector pili.  It also increases the secretion of sweat.
  • 34. 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.
  • 35. 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 gastrointestinal (GI) tract 3. Arrector pili of skin 4. Gallbladder
  • 36. 5. Uterus 6. Dilator pupillae of iris 7. Nictitating membrane of cat.
  • 37.  Catecholamines cause relaxation of smooth muscles in the following organs: 1. Non-sphincteric part of GI tract (esophagus, stomach and intestine) 2. Bronchioles 3. Urinary bladder
  • 38. 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.
  • 39. 11. Other Effects of Catecholamines 1. On salivary glands (via alpha and beta-2 receptors):  Cause vasoconstriction in salivary gland, leading to mild increase in salivary secretion 2. On sweat glands (via beta-2 receptors):  Increase the secretion of apocrine sweat glands 3. On lacrimal glands (via alpha receptors):  Increase the secretion of tears
  • 40. 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 rennin secretion from juxtaglomerular apparatus of the kidney
  • 41.
  • 42.  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 sympatho-adrenal 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.
  • 43.
  • 44.  Dopamine  Secreted by adrenal medulla.  Also secreted by dopaminergic neurons in some areas of brain, particularly basal ganglia.  In brain, this hormone acts as a neurotransmitter.
  • 45.  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 but does not affect diastolic blood pressure.