2. • Some preganglionic sympathetic fibres end on the
secretory cells in adrenal medulla.
• The cells in adrenal medulla is postganglionic neurons
that lost their axon to become secretory cells.
DEPT. OF PHYSIOLOGY, GMCM 3
4. The adrenal medulla bridges the endocrine and
sympathetic nervous system.
DEPT. OF PHYSIOLOGY, GMCM 5
5. Specific Learning Objectives
• Adrenal Medulla- Morphology and its Hormones
• Catecholamines- Synthesis and Catabolism
• Catecholamines - Mechanism of Action
• Effects of Epinephrine and Norepinephrine
• Effects of Dopamine
• Regulation of catecholamine secretion
• Applied Aspects
DEPT. OF PHYSIOLOGY, GMCM 6
DEPT. OF PHYSIOLOGY, GMCM
6. • Constitutes 28% of the mass of the adrenal gland.
• Made up of interlacing cords of densely innervated
granule-containing cells.
Adrenal Medulla
DEPT. OF PHYSIOLOGY, GMCM 7
8. • Chromaffin cells : Ectodermal origin; from neural crest
• Secrete catecholamines
1. Epinephrine
2. Norepinephrine
3. Dopamine – small amounts
DEPT. OF PHYSIOLOGY, GMCM 9
9. • Two cell types
1. Epinephrine-secreting - larger, less dense granules
2. Norepinephrine-secreting - smaller, very dense granules
• In humans, 90% of the cells are the epinephrine-secreting
and 10% are the norepinephrine-secreting.
DEPT. OF PHYSIOLOGY, GMCM 10
10. Adrenal medullary hormones are not essential for life,
but help to deal with emergency.
DEPT. OF PHYSIOLOGY, GMCM 11
11. In the granulates vesicles ,
• Norepinephrine & Epinephrine are bound to ATP
• Associated with a protein called chromogranin A
• Hormones released from by exocytosis
DEPT. OF PHYSIOLOGY, GMCM 12
16. Paraganglia
• Small group of cells resembling those in medulla.
• Found near thoracic and abdominal sympathetic ganglia.
DEPT. OF PHYSIOLOGY, GMCM 17
17. Blood Supply
• From Phrenic Artery, Renal Artery, Aorta
• Drains → Central Adrenal Vein
• Right→ IVC, Left → Left Renal Vein
DEPT. OF PHYSIOLOGY, GMCM 18
18. Nerve Supply
• Preganglionic sympathetic cholinergic fibers from T4-T9.
• Through the splanchnic nerve.
DEPT. OF PHYSIOLOGY, GMCM 19
19. Specific Learning Objectives
• Adrenal Medulla- Morphology and its Hormones
• Catecholamines- Synthesis and Catabolism
• Catecholamines - Mechanism of Action
• Effects of Epinephrine and Norepinephrine
• Effects of Dopamine
• Regulation of catecholamine secretion
• Applied Aspects
DEPT. OF PHYSIOLOGY, GMCM 20
DEPT. OF PHYSIOLOGY, GMCM
20. A. Biosynthesis of Adrenal Medullary Hormones
• Norepinephrine is formed by hydroxylation and de-
carboxylation of tyrosine.
• Epinephrine formed by methylation of Norepinephrine
DEPT. OF PHYSIOLOGY, GMCM 21
22. Phenylalanine
↓ PA hydroxylase , THB
Tyrosine
↓ Tyrosine hydroxylase , THB
DOPA
↓ Dopa decarboxylase ,PLP
Dopamine
↓ Dopamine-β-hydroxylase , vit C
Norepinephrine
↓ PNMT , SAM
Epinephrine
23
23. • Phenylalanine hydroxylase is found in liver
• Rate limiting step: Tyrosine → DOPA
• Tyrosine hydroxylase is subject to feedback inhibition
by NE & DA → internal control of synthetic process
DEPT. OF PHYSIOLOGY, GMCM 24
24. • Role of glucocorticoids
1. PNMT is induced by glucocorticoids
2. Glucocorticoids are also necessary for normal
development of adrenal medulla
DEPT. OF PHYSIOLOGY, GMCM 25
26. • E and NE : O-Methylated by COMT to metanephrine
and normetanephrine and are excreted in urine
• Some oxidized by MAO → VMA
• Some O-methylated derivatives conjugated to
sulphates & glucuronides.
B. Catabolism of Catecholamines
DEPT. OF PHYSIOLOGY, GMCM 27
28. • End product of DA catabolism – Homovanilic acid
( HVA )
• Most of Epinephrine released at nerve endings re-
enter nerve endings.
DEPT. OF PHYSIOLOGY, GMCM 29
29. Applied Aspect - Phenylketonuria
• Accumulation of phenylalanine and its derivatives in
blood, tissues and urine.
• Cause severe mental retardation.
DEPT. OF PHYSIOLOGY, GMCM 30
30. • Mutation of gene for phenylalanine hydroxylase.
• Can also be due to tetrahydrobiopterin deficiency.
• Here catecholamine & serotonin deficiency also present.
DEPT. OF PHYSIOLOGY, GMCM 31
32. Specific Learning Objectives
• Adrenal Medulla- Morphology and its Hormones
• Catecholamines- Synthesis and Catabolism
• Catecholamines - Mechanism of Action
• Effects of Epinephrine and Norepinephrine
• Effects of Dopamine
• Regulation of catecholamine secretion
• Applied Aspects
DEPT. OF PHYSIOLOGY, GMCM 33
DEPT. OF PHYSIOLOGY, GMCM
33. • Epinephrine and Norepinephrine act on α and β
receptors.
• Dopamine acts on D Receptors.
• These are G - protein coupled receptors
DEPT. OF PHYSIOLOGY, GMCM 34
34. Receptor Mechanism of Action
α1 (+) PL C, ↑ IP3 DAG
α2 ↓ cAMP
β1 ↑ cAMP
β2 ↑ cAMP
β3 ↑ cAMP
DEPT. OF PHYSIOLOGY, GMCM 35
35. Receptor Mechanism of Action
D1, D5 (+) AC → cAMP
D2, D3, D4 (-) AC
DEPT. OF PHYSIOLOGY, GMCM 36
36. α Receptors
Receptor Sites Effects
α1 Blood vessels except
vessels of skeletal
muscles
Vasoconstriction
Pupillary dilatation
Piloerection
Contract intestinal sphincters
Contract bladder sphincters
α2 Presynaptic sites Inhibit the release of NE
DEPT. OF PHYSIOLOGY, GMCM 37
38. DEPT. OF PHYSIOLOGY, GMCM 39
Specific Learning Objectives
• Adrenal Medulla- Morphology and its Hormones
• Catecholamines- Synthesis and Catabolism
• Catecholamines - Mechanism of Action
• Effects of Epinephrine and Norepinephrine
• Effects of Dopamine
• Regulation of catecholamine secretion
• Applied Aspects
DEPT. OF PHYSIOLOGY, GMCM
39. The relative effects of Norepinephrine and Epinephrine
are determined by the types of receptors in the organ.
DEPT. OF PHYSIOLOGY, GMCM 40
40. Epinephrine and Norepinephrine act on α and β receptors.
Epinephrine Norepinephrine
Excites both α and β receptors equally Has greater affinity for α receptors
Is more potent on β receptors than NE Excites β receptors to a lesser extend
DEPT. OF PHYSIOLOGY, GMCM 41
41. • Mimics the effect of sympathetic nervous discharge
• The effect lasts 5 – 10 times longer - hormones are
removed from blood slowly over a period of 2 – 4 min.
DEPT. OF PHYSIOLOGY, GMCM 42
42. Effects of Epinephrine and Norepinephrine
1. Metabolic Effects
2. Systemic Effects
DEPT. OF PHYSIOLOGY, GMCM 43
46. C. Mineral metabolism
• Play an important role in K+ distribution
• When Epinephrine & Norepinephrine is injected
Initial rise in plasma K+
→ release of K+ from the liver
Prolonged fall in plasma K+
→ ↑ entry of K+ into skeletal muscle
DEPT. OF PHYSIOLOGY, GMCM 47
47. 1. Action on Heart
• Norepinephrine and Epinephrine increase force &
rate of contraction of isolated heart (β1).
• Also ↑ myocardial excitability.
• Can lead to extrasystoles and cardiac arrhythmias.
Systemic Effects
DEPT. OF PHYSIOLOGY, GMCM 48
48. 2. Action on blood vessels
Epinephrine
• Dilates blood vessels in skeletal muscles and liver (β2).
• Overbalances vasoconstriction produced by elsewhere.
• Net vasodilator.
• So the total peripheral resistance drops.
DEPT. OF PHYSIOLOGY, GMCM 49
49. • SBP Increases
• DBP Decreases (↓ Peripheral Resistance)
• Wide Pulse pressure
• BR stimulation is insufficient to obscure direct cardio
acceleratory effect
• HR and Cardiac output ↑es
DEPT. OF PHYSIOLOGY, GMCM 50
54. 3. Action on GIT
• Relaxation of GI smooth muscles and contraction of
sphincters.
4. Action on Urinary Bladder
• Relaxation of detrusor muscles and contraction of
trigone and sphincter.
DEPT. OF PHYSIOLOGY, GMCM 55
55. 5. Action on eye
• Dilatation of pupil, relaxation of ciliary muscles -
better for vision.
6. Effect on respiratory system
• Relaxation of bronchial muscles
DEPT. OF PHYSIOLOGY, GMCM 56
56. 7. Effect on skeletal muscles
• Epinephrine ↑ force of contraction of skeletal muscles
• ↑ blood supply to skeletal muscles
8. Effect on CNS
• ↑ alertness
DEPT. OF PHYSIOLOGY, GMCM 57
57. 9. Effect on endocrine system
1. ↑ renin secretion
2. ↑ ADH secretion
3. ↑ thyroid hormone secretion
DEPT. OF PHYSIOLOGY, GMCM 58
58. DEPT. OF PHYSIOLOGY, GMCM 59
Specific Learning Objectives
• Adrenal Medulla- Morphology and its Hormones
• Catecholamines- Synthesis and Catabolism
• Catecholamines - Mechanism of Action
• Effects of Epinephrine and Norepinephrine
• Effects of Dopamine
• Regulation of catecholamine secretion
• Applied Aspects
DEPT. OF PHYSIOLOGY, GMCM
59. Dopamine
• NT in certain parts of brain like Basal Ganglia.
• Dopamine is metabolized to inactive compounds by
MAO and COMT.
• 5 types of receptors D1 – D5.
DEPT. OF PHYSIOLOGY, GMCM 60
60. Physiological function of dopamine in circulation
• Injected dopamine causes vasodilation in kidney and
mesentery.
• Produces vasoconstriction elsewhere probably by
releasing NE.
• Positive ionotropic effect on heart.
DEPT. OF PHYSIOLOGY, GMCM 61
61. Net effect of moderate doses of dopamine
• ↑ SBP
• Dopamine is useful in the treatment of traumatic
and cardiogenic shock
DEPT. OF PHYSIOLOGY, GMCM 62
62. DEPT. OF PHYSIOLOGY, GMCM 63
Specific Learning Objectives
• Adrenal Medulla- Morphology and its Hormones
• Catecholamines- Synthesis and Catabolism
• Catecholamines - Mechanism of Action
• Effects of Epinephrine and Norepinephrine
• Effects of Dopamine
• Regulation of catecholamine secretion
• Applied Aspects
DEPT. OF PHYSIOLOGY, GMCM
63. Mainly neural regulation
• Catecholamine secretion is low in basal state.
• Reduced during sleep.
Stimuli for secretion
• Anxiety, pain, trauma
• hypovolemia
• hypothermia
DEPT. OF PHYSIOLOGY, GMCM 64
65. Secretion of epinephrine and norepinephrine from the adrenal
medulla is
DEPT. OF PHYSIOLOGY, GMCM 66
regulated primarily by descending sympathetic
signals in response to various forms of various forms of
stress - exercise, hypoglycemia, hemorrhagic, hypovolemia etc.
66. • Descending sympathetic signals
• Ach binds to nicotinic receptors on chromaffin cells.
• ↑ synthesis and release of catecholamines.
• Increased adrenal medullary secretion in emergency
situations, the preparation for flight/ fight.
DEPT. OF PHYSIOLOGY, GMCM 67
67. DEPT. OF PHYSIOLOGY, GMCM 70
Specific Learning Objectives
• Adrenal Medulla- Morphology and its Hormones
• Catecholamines- Synthesis and Catabolism
• Catecholamines - Mechanism of Action
• Effects of Epinephrine and Norepinephrine
• Effects of Dopamine
• Regulation of catecholamine secretion
• Applied Aspects
DEPT. OF PHYSIOLOGY, GMCM
68. 1. Pheochromocytoma
• Mainly adrenal medullary tumour.
• Tumour of chromaffin tissue that produces excessive
catecholamines.
• Catecholamine frequently elevated is norepinephrine,
sometimes epinephrine or both.
DEPT. OF PHYSIOLOGY, GMCM 71
69. • Symptoms are episodic rather than continuous in
epinephrine secreting tumour.
• Symptoms
1. Hypertension
2. Headache
3. Sweating
4. Palpitation
DEPT. OF PHYSIOLOGY, GMCM 72
70. Treatment
• Medical treatment
• α-blockers pre operative
• Surgical excision – definitive treatment
DEPT. OF PHYSIOLOGY, GMCM 73
71. 2. Therapeutic Uses
Adrenaline
• Anaphylactic shock, allergy
• Acute severe asthma
• Cardiac arrest
Dopamine or Noradrenaline
• Shock
DEPT. OF PHYSIOLOGY, GMCM 74
72. Specific Learning Objectives
✓Adrenal Medulla- Morphology and its Hormones
✓Catecholamines- Synthesis and Catabolism
✓Catecholamines - Mechanism of Action
✓Effects of Epinephrine and Norepinephrine
✓Effects of Dopamine
✓Regulation of catecholamine secretion
✓Applied Aspects
DEPT. OF PHYSIOLOGY, GMCM 75
DEPT. OF PHYSIOLOGY, GMCM
