ADRENAL MEDULLA
Dr JOSHUA TUGUMISIRIZE
YEAR 2
OCTOBER 2024
OBJECTIVES
Demonstrate structure and functional relationship of the adrenal
medulla and adrenal cortex
Outline the steps in the synthesis of catecholamines hormones
Outline the functions of catecholamines hormones
Explain the role of catecholamines in metabolism and stress response
Give examples of abnormalities of function of adrenal medulla
LOCATION OF ADRENAL GLANDS
LOCATION OF HUMAN ADRENAL
GLANDS
BLOOD SUPPLY
LIFE SAVING GLANDS
Adrenal glands have been described as life saving glands or Essential
glands.
If adrenal glands in mice are removed, the mice die with several days (3
to 15 days)
Without adrenal glands, animals cannot withstand stress.
STRUCTURAL FEATURES
GUYTON’S VERSION OF ADRENAL GLAND
KEY POINTS ABOUT ADRENAL GLANDS
They are two, each sits at pole of the kidney (supra renal)
Each is 4 g
Each adrenal gland consists of the adrenal cortex (80%) and the adrenal
medulla (20%)
The adrenal cortex is made up of three zone above
Zona Glomerulosa – outer zone, contributes 15 %
Zona Fasciculata- middle zone, overs about 75%
Zona Reticularis – the innermost zone
HORMONES OF THE ADRENAL GLANDS
ADRENAL MEDULLA
The adrenal medulla is modified postganglionic sympathetic neurones:
The effector cells are called chromaffin cells
They originate in the neural crest
The main stimulus is through the pre-ganglionic cholinergic fibres
Glucocorticoids are necessary for the development of the adrenal
medulla
In 21 β-hydroxylase deficiency, glucocorticoid secretion is reduced during
fetal life and the adrenal medulla is dysplastic
In untreated 21 β-hydroxylase deficiency, circulating catecholamines are
low after birth.
CELL TYPES IN ADRENAL MEDULLA
Adrenaline secreting type: 90% of the cells in the medulla; large, less
dense granules,
Noradrenaline secreting type: 10% of the cells in the medulla small
size ; very dense granules
MAIN SECRETIONS OF ADRENAL MEDULLA
Noradrenaline (Norepinephrine)
Adrenaline (Epinephrine)
Dopamine
These hormones are synthesized from tyrosine
Through hydroxylation and decarboxylation to produce noradrenaline
And through methylation of noradrenaline to produce adrenaline
Storage granules with ATP : chromogranin A
PLASMA HORMONE LEVELS
In recumbent humans, the plasma of free noradrenaline is about 300pg/mL
(1.8nmol/L). On standing, the level increases 50 – 100%
Adrenaline : 3 µg/dl ( 0.16 nmol/L)
Noradrenaline 30 µg/dl
Dopamine 3.5 µg/dl
After adrenelectomy, plasma level of noradrenaline is unchanged, but the level of
adrenaline falls to zero
Half-life – 2-3 minutes
Noradrenaline broken down to vanillylmandelic acid (VMA)
SYNTHESIS OF CATECHOLAMINES
Uptake of tyrosine into chromaffin cells is by active transport
Conversion of tyrosine to dihyroxyphenylalanine (DOPA) by hydroxylation in the
presence of tyrosine hydroxylase
Decarboxylation of DOPA into dopamine is by DOPA decarboxylase
The dopamine enters granules of the chromaffin cells
Hydroxylation of dopamine into noradrenaline is by the enzyme dopamine beta-
hydroxylase
Noradrenaline is released from the granules into the cytoplasm
Methylation of noradrenaline into adrenaline is by the important enzyme:
phenylethanolamine -N –methyltransferase (PNMT). PNMT is present in
chromaffin cells (and also in the brain)
SYNTHESIS OF CATECHOLAMINES
ALTERNATIVE: SYNTHESIS OF CATECHOLAMINES
PEPTIDES IN MEDULLA
Opiod peptides
-most of the circulating metenkaphalin comes from the adrenal
medulla
Adrenomedullin
TRANSPORT OF NORADRENALINE AND ADRENALINE
Noradrenaline and adrenaline are bound to ATP and associated with a
protein called chromogranin A.
The catecholamines are transported into the granulated vesicles by two
vesicular transporters
They are released from adrenal cells by exocytosis
PHYSIOLOGICAL AND PATHOLOGICAL CHANGES IN HUMAN VENOUS BLOOD
METABOLIM AND EXCRETION
Methoxylation of adrenaline into meta-adrenaline and noradrenaline into
metanoradrenaline in the presence of ‘catecholamine-N-methyltransferase
(COMT).
Meta-adrenaline and metanoradrenaline are together called metanephrines
Metanephrines are oxidized into vanillylmandelic acid (VMA) by mono-amine
oxidase (MAO)
Catecholamines are excreted in urine in three forms
1 free adrenaline and free noradrenaline – 15%
2 conjugated meta-adrenaline and metanoradrenaline – 50%
3 vanillylmandelic acid (VMA)- 35%
METABOLISM OF CATECHOLAMINES
RECEPTORS
Most cells of the body have receptors for catecholamines
Alpha 1, Alpha 2
Beta 1 Beta 2
They are all transmembrane proteins . They are G – protein coupled receptors
Epinephrine is equally active on alpha and beta receptors
Norepinephrine is active mainly on alpha and much less on beta receptors ;
Beta receptors act by increasing levels of cAMP. Alpha 2 receptors act by
decreasing levels of cAMP. Alpha 1 produce change in intracellular calcium
levels
ADRENERGIC RECEPTORS
ACTIONS OF CATECHOLAMINES
CATECHOLAMINE RESPONSE TO HYPOGLYCAEMIA
ACTION ON THE LIVER AND ADIPOSE TISSUE
Catecholamines act on the liver to produce Glucose
- Hydrolysis of glycogen
- Stimulate gluconeogenesis from lactic acid and amino acids
- Catecholamines stimulate production of glucagon (alpha cells) and
inhibit production of insulin (beta cells)
- Mobilization of free fatty acids from adipose tissue (in the presence of
glucocorticoids)
ACTION ON BETA RECEPTORS
EFFECT OF CATECHALAMINES ON THE HEART
Both adrenaline and noradrenaline act on the β1 receptors
Their effects:
-Increase in myocardial excitability (may cause extrasystoles and
occasionally arrhythmias
-
EFFECT ON BLOOD PRESSURE
Adrenaline increase systolic blood pressure- by increasing force of
contraction of the heart and cardiac output BUT it decreases diastolic
pressure by vasodilation in blood vessels in skeletal muscle (decreasing
total peripheral resistance)
Noradrenaline increases diastolic pressure by general vasoconstriction
thereby increasing total peripheral resistance. It also increases systolic
blood pressure by its action on the heart.
Glucocorticoids have a permissive action to catacholamines
MORE ON FUNCTIONS OF CATECHOLAMINES
Beta 1 receptors in the heart
Activated by both noradrenaline and adrenaline
Increased rate and force of contraction of the heart (chronotropic effect
and inotropic effect).
Incresed conductivity of the heart (dromotropic effect)
Noradrenaline produces vasoconstriction in most organs through the
alpha receptors
Adrenaline causes vasodilatation in skeletal muscles, and liver through
the beta 2 receptors.
ON RESPIRATION
Via beta 2 receptors
Adrenaline increases the rate and force of respiration
It causes bronchodilatation
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 causes vasodilation in skeletal muscle
ON SMOOTH MUSCLE
Via alpha and beta receptors
Contraction of smooth muscles:
-splenic capsule
-sphincters of GIT tract
-Arrector pili of skin
-Gall bladder
-Uterus
-Dilator pupillae of iris
Catecholamines cause relaxation of smooth muscles of
-esophagus
-stomach
-intestine
Bronchioles
Urinary bladder
ON SKIN
Via alpha and beta 2 receptors
Adrenaline causes contraction of erector pili
It increases the secretion of sweat
ON NERVOUS SYSTEM
Through beta receptors
Adrenaline increases the activity of the brain
Adrenaline secretion increases during ‘fight or flight reactions’ after exposure
to stress
The main stimuli: pain, anxiety, trauma, hypovolaemia, hypoglycaemia,
hypothermia act on hypothalamus (medulla and pons)
General increase in arousal
Pathways
-sympathoadrenal medullary system
-hypothalamic-pituitary-adrenal cortex axis
THE STRESS RESPONSE
STIMULI
Secretion of catecholamines increase in response to hypoglycaemia.
There are cells in the CNS that monitor glucose levels
NEURAL PATHWAY
Preganglion cholinergic nerve terminals terminate in the cells in the
adrenal medulla
Postganglion ‘Cells’ are the chromaffin cells
NEURAL CONTROL AND THE STRESS RESPONSE
In emergency stress situations the ‘sympathoadrenal system’ is
activated –the flight or fight response !
NEURAL PATHWAY
DOPAMINE
Physiological effect of dopamine is unknown.
Dopamine is produced is made in the renal cortex. It causes natriuresis.
It may exert its effect by inhibiting renal Na-K ATPase.
Injected dopamine cause renal vasodilatation.
It also produces vasodilation in the mesentery
It may produce noradrenaline, that may act on beta1 receptors and
lead to increase id systolic pressure and change in diastolic pressure
Dopamine is useful in treatment of traumatic and cardiogenic shock
WHAT CAN GO WRONG?
Pheochromocytoma – tumour of chromophil cells in adrenal
medulla and excessive secretion of noradrenaline and adrenaline
Rarely it may be due to tumour of sympathetic ganglia
Major features include high blood pressure (hypertension),
anxiety, sweating, nervousness, pallor, tachycardia; chest pain,
fever, headache, glycosuria
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