Hormones of adrenal medulla.functions of hormones,applied aspects

1. Adrenal Gland:
The Adrenal Medulla

2. The student will be able to: (MUST KNOW)
1. Give the structural organization of adrenal glands.
2. Name the hormones secreted from adrenal glands.
3. List the hormones secreted from adrenal medulla.
4. Give the steps of synthesis of catecholamines.
5. Apply the knowledge of understanding metabolism of catecholamines in diagnosing the excess or
deficiency of catecholamines.
6. Describe the functions of catecholamines.
7. Classify and understand the difference between the functions of epinephrine and norepinephrine,
especially their cardiovascular effects.
8. Outline the role of catecholamines in fight or flight response.
9. Learn the physiological basis of features, diagnosis, and treatment of pheochromocytoma.
LEARNING OBJECTIVES

3. •There are two adrenal glands, each one located at the upper pole of each kidney.
• Each adrenal gland consists of two distinct endocrine glands, one surrounding
the other: the inner adrenal medulla, surrounded by the outer adrenal cortex.
•The adrenal cortex consists of three layers.
1. The outer zone of adrenal gland, i.e. the adrenal cortex forms about 80–90% of
the total gland, the inner zone, i.e. the adrenal medulla consists of 10–20% of
the gland.
2. Developmentally and functionally, these glands are two separate endocrine
organs.
• Adrenal cortex develops from the mesodermal tissue and secretes steroid
hormones.
• Adrenal medulla develops from neuroectodermal tissue related to
sympathetic ganglia, and therefore secretes catecholamines.
FUNCTIONAL ANATOMY

4. Fig. 112.1: Location of the adrenal (suprarenal) gland

5. The weight of each adrenal gland is about 5–10 g.
The gland is highly vascular and receives blood from three sources:
branches of aorta, renal arteries, and phrenic arteries.
• The arterial blood enters the sinusoidal capillaries in the cortex and
then drains into the medullary venules.
• This arrangement exposes the medulla to the high concentration of
corticosteroids secreted from the cortex
BLOOD SUPPLY

6. The adrenal glands are essential for survival. In general, they play an
important role in following physiological processes of the body:
1. Homeostasis of energy stores
2. Control of fluid volume and extracellular environment of cells
3. Supply of substrates for generation of ATP in the cells
4. Regulation of intermediary metabolisms
5. Control of immunological mechanisms
6. Regulation of functions of various organ systems
GENERAL IMPORTANCE

7. Unlike hormones of the adrenal cortex, adrenomedullary hormones are not
very essential for survival.
However, they help the individual to cope with emergencies.
Adrenal medulla by secreting catecholamines assists the individual to
prepare for fight or flight responses and also assists in meeting the
metabolic requirements of the body in hypoglycemic emergencies in
addition to their effects on other systemic functions.
ADRENAL MEDULLA

8. Adrenal Medulla
 Medullary cells are derived from the embryonic neural crest,
simply modified neurons (Chromaffin cells,
also pheochromocytes).
 Innervated by cholinergic preganglionic sympathetic neurons

9. Adrenal Medulla: A Modified Sympathetic Ganglion

10. The major hormones secreted from the adrenal medulla are catecholamines:
1. Epinephrine
2. Norepinephrine
3. Dopamine
In addition to secretion of catecholamines, the gland also secretes following
peptides:
1. Adrenomedullin
2. Enkephalins
3. β-endorphin
4. Neuropeptide-Y
5. Chromogranin
ADRENOMEDULLARY HORMONES

11. Synthesis and Secretion
Catecholamines are synthesized from the amino acid phenylalanine
and tyrosine.
1. Conversion of tyrosine to Dopa is catalyzed by tyrosine
hydroxylase and dopa to dopamine by dopa decarboxylase.
2. Norepinephrine is formed by hydroxylation and decarboxylation
of tyrosine.
3. Epinephrine is formed by methylation of norepinephrine by
phenylethanolamine-N-methyltransferase (PNMT).
4. After synthesis, the hormones are stored in the granules of
chromaffin cells before they are secreted.
SYNTHESIS, SECRETION, AND METABOLISM OF
CATECHOLAMINES

12. Flowchart 112.1:
Synthesis of
adrenomedullary
hormones.

13. Catecholamine secretion from the adrenal medulla increases in following
conditions.
1. Exercise
2. Hypoglycemia
3. Trauma (physical injury)
4. Anger and anxiety
5. Pain
6. Cold.
The main mechanism of secretion in these conditions is sympathetic stimulation.
• Hypoglycemia is a strong stimulus for catecholamine release.
REGULATION OF SECRETION

15. Flowcharts 112.2A and
B: Metabolic degradation
of epinephrine (A)
and norepinephrine (B).
METABOLISM

16. Flowchart 112.3: Steps of
metabolic degradation of
dopamine.
DEGRADATION

17. Metabolism of Catecholamines
 Two primary enzymes are involved in the degradation of
catecholamines:
1. monoamine oxidase (MAO) and
2. catechol-O-methyltransferase (COMT).
 Urinary vanillylmandelic acid (VMA) and metanephrine
are sometimes used clinically to assess the level of
catecholamine production in a patient.

18. Catecholamines act on α and β receptors. There are three types of β receptors:
β1, β2, and β3, and two types of α receptors: α1 and α2.
1. The α1 and α2 receptors have three subtypes each.
2. Epinephrine and norepinephrine act on both α and β receptors
3. The β1, β2, and β3 receptors are coupled to adenylylcyclase; therefore,
catecholamine action through these receptors is mediated by increase in cAMP
in the cell
4. The α2 receptor is coupled to inhibitory G protein; therefore, binding of
catecholamines with this receptor decreases cAMP in the cells.
5. The α1 receptor is coupled to phosphatidylinositol in the membrane
MECHANISM OF ACTION

20. Adrenergic Receptors
 Alpha-Adrenergic Receptors
 1: vasoconstriction, intestinal relaxation, uterine
contraction, pupillary dilation
 2: platelet aggregation,vasoconstriction,  insulin secretion
 Beta-Adrenergic Receptors
 1:  HR/contractility,  lipolysis,  renin secretion
 2: vasodilation, bronchodilation,  glycogenolysis
 3:  lipolysis,  brown fat thermogenesis

21. Functions of catecholamines
1. Effect on carbohydrate metabolism: Both of them can increase
glycogenolysis and gluconeogenesis and decrease glycogenesis.
i. Catecholamine promote the release of glucose from liver and decrease
its utilization by muscle;
ii. ii. Epinepherine inhibits insulin secretion but promote glucagon secretion.
2. Effect on lipid metabolism: Both of them enhance the breakdown of
TAG in adipose tissue (lipolysis).
This cause increase in the free fatty acid in the circulation which are
effectively utilized by the heart and muscle as fuel source.
3. Effect on physiological function: Catecholamines increase cardiac
output, blood pressure and oxygen consumption.
They cause smooth muscle relaxation in bronchi, GIT and blood vessels
supplying skeletal muscle.

22. Exercise as an example of Adrenal Medulla activation
 Exercise is similar to the “fight-or-flight” response but
without the subjective element of fear.
 It involves a greater adrenomedullary response (i.e.,
endocrine role of epinephrine) than a sympathetic nervous
response (i.e., neurotransmitter role of norepinephrine).

 The overall goal of the sympathoadrenal system during
exercise is to meet the increased energy demands of skeletal
and cardiac muscle while maintaining sufficient oxygen and
glucose supply to the brain.

23. Differences between Epinephrine and
Norepinephrine
 Epinephrine >> norepinephrine – in terms of cardiac
stimulation leading to greater cardiac output (
stimulation).
 Epinephrine < norepinephrine – in terms of constriction
of blood vessels – leading to increased peripheral
resistance – increased arterial pressure.
 Epinephrine >> norepinephrine –in terms of increasing
metabolism.

25. A case study?
“ A 35-year-old husband and father of three children,
has been experiencing headaches and palpitations of
increasing frequency and severity over the past six
months. In addition, he has had periods of intense
anxiety and panic attacks. What may be the probable
diagnosis?

26. Pheochromocytoma
 Pheochromocytoma is a tumor of the adrenal medulla that occurs due to
hyperplasia of chromaffin cells.
 Most of pheochromocytomas produce both epinephrine and norepinephrine.
Therefore, the concentration of epinephrine and norepinephrine is very high.
APPLIED PHYSIOLOGY

27. Features
The most common feature is sustained hypertension.
1. The disease is associated with
 increased metabolic rate,
 profuse sweating,
 extreme tachycardia and
 high BP,
 hyperglycemia, and
 loss of appetite and body weight.

28. 2. In this disease, though there is continuously high secretion of
catecholamines, typically there are episodes of excess
catecholamine release.
3. The burst of catecholamine secretion usually occurs
following rapid change in posture or the regular
physiological events that stimulate the sympathetic system.
4. This manifests with severe headache, tachycardia,
palpitation, extreme anxiety, perspiration, either pallor or flushing,
severe rise in blood pressure, and a feeling of impending death.

29. Diagnosis
Diagnosis is established by detecting increased concentration of
catecholamines in blood when the patient is in recumbent and at rest.
Urinary excretion of metanephrine and VMA also increases.
Treatment
Treatment is by surgical removal of the tumor.