ADRENAL MEDULLA
ADRENAL MEDULLA
• Inner part of adrenal gland
• Neural in origin
• Formed in parallel with peripheral nervous
system
• Composed of chromaffin cells
(phaeochromocytes) with wide venous
sinusoids permeating between them
HORMONES PRODUCED
• Catecholamines
– Epinephrine
(adrenaline) 80-90%
– Norepinephrine
(noradrenaline) 10-20%
– Dopamine
General features of adrenal medullary
secretion
• Half-life of the catecholamines is only about 2
minutes. Metabolic end-products include
metanephrines and vanillylmandelic acid
(VMA) both of which can be measured in
plasma and urine
• Removal of the adrenal medulla reduces
plasma epinephrine to very low levels but
does not alter plasma norepinephrine.
Difference between the actions of epinephrine
and norepinephrine
• First, epinephrine, has greater effect in
stimulating the beta receptors, has a greater
effect on cardiac stimulation than does
norepinephrine.
• Second, epinephrine causes only weak
constriction of the blood vessels in the muscles,
in comparison with much stronger constriction
caused by norepinephrine.
• A third difference; Epinephrine has 5 to 10 times
as great a metabolic effect as norepinephrine.
General features of adrenal medullary secretion
• Because many of the actions of epinephrine are also
mediated by nor-epinephrine, the adrenal medulla is
not essential for life.
• The vasoconstrictive action of norepinephrine is
essential for the maintenance of normal blood
pressure, especially when an individual is standing.
Plasma norepinephrine levels double when one goes
from a lying to a standing position. People with
inadequate production of nor-epinephrine suffer from
orthostatic hypotension.
• Epinephrine is a stress hormone and rapidly increases
in response to exercise, exposure to cold, emergencies,
and hypoglycemia
Major metabolic actions of epinephrine
• Liver: Epinephrine increases the activity of liver and muscle
phosphorylase, promoting glycogenolysis. This increases
glucose output by the liver.
• Skeletal muscle: Epinephrine promotes glycogenolysis but
because muscle lacks glucose-6-phosphatase, glucose cannot
be released by skeletal muscle; instead, it must be
metabolized at least to lactate before being released into the
circulation.
• Adipose tissue: Epinephrine increases lipolysis in adipose
tissue by increasing the activity of hormone-sensitive lipase.
Glycerol from TG breakdown is a minor substrate for
gluconeogenesis.
• Epinephrine increases the metabolic rate. This will not occur
without thy-roid hormones or the adrenal cortex
Physiological actions of catecholamines
• Role in stress & emotions
– Catecholamines participate along with
sympathetic nervous system
– Brings about changes in various body systems &
metabolism to meet the effect of stress effectively
– Fright, fight or flight reaction (emergency)
Circulatory changes produced in humans by the slow
intravenous infusion of epinephrine and norepinephrine
EFFECTS OF CATECHOLAMINES ON CVS
On total peripheral
resistance
On heart rate
Epinephrine
Epinephrine
• Vasodilation
so ↓ TPR
Norepinephrine
• Vasoconstriction
so ↑ TPR
• ↑ HR & force of
contraction (Direct
action)
Norepinephrine
• ↓ HR (Reflex
mechanism) - Marey’s
reflex
EFFECTS OF CATECHOLAMINES ON CVS
ON BLOOD PRESSURE
ON CARDIAC OUTPUT
EPINEPHRINE
EPINEPHRINE
• ↑ SBP
– DUE TO INCREASED H.R.
• ↓ DBP
– DUE TO VASODILATION
• ↑ PULSE PRESSURE
• ↑ C.O.
NOREPINEPHRINE
• ↓ C.O.
• ↑ BOTH SBP & DBP
• ↓ / N PULSE PRESSURE
DUE TO DIRECT EFFECT
H.R.
NOREPINEPHRINE
DUE TO ↓ HR
Applied aspects - PHAEOCHROMOCYTOMA
• Tumours of adrenal
medulla
• Usually benign
• Secrete large amounts
of epinephrine &
norepinephrine
Features :
•
•
•
•
•
•
•
•
Hypertension
Headache
Sweating
Palpitation
Anxiety
Increased body
temperature
Hyperglycemia
Increased urinary
excretion of
catecholamines,
metanephrines and VMA
• Paragangliomas are extrarenal
pheochromocytomas of sympathetic ganglia
located primarily within the abdomen and that
secrete norepinephrine.
• Pheochromocytomas are highly vascular and
encapsulated.
• Episodic release of hormone, particularly when it
is mainly norepinephrine, can abruptly cause a
hypertensive crisis. Can be induced by physical
stimuli that displaces abdominal contents.
• Most reliable screening is plasma or urine
metanephrines.
• Usually curable but can be fatal if undiagnosed
Helen Ames is a 51-year-old homemaker who
experienced what she thought were severe menopausal
symptoms. These awful “attacks” were becoming more
frequent. Her heart raced and pounded; she had a
throbbing headache and visual disturbances; she felt
hot, but her hands and feet were cold; and she was
nauseated, sometimes to the point of vomiting. Mrs.
Ames called her physician, who agreed that the
symptoms were probably menopausal and prescribed
hormone replacement therapy over the phone. Mrs.
Ames took the hormones (a combination of estrogen
and progesterone), but they did not relieve her
symptoms. The attacks were occurring almost daily. She
made an appointment with her physician.
In the physician’s office, Mrs. Ames’ blood pressure was
severely elevated at 200/110, and her heart rate was
increased at 110 beats/min. To rule out a
pheochromocytoma (a rare tumor of the adrenal medulla),
the physician ordered a 24-hour urine measurement of
vanillylmandelic acid (VMA). To his surprise, the results of
the 24-hour urinary VMA test were positive, a finding that
provided nearly conclusive evidence of a
pheochromocytoma. A computed tomographic scan
confirmed that Mrs. Ames had a 3-cm mass on her right
adrenal gland. While awaiting surgery to remove the tumor,
she was given phenoxybenzamine, an α1-adrenergic
antagonist. After an appropriate dosage of
phenoxybenzamine was established, she was also given a
low dose of propranolol, a β-adrenergic antagonist. She was
cleared for surgery when the medications had decreased
her blood pressure to 140/90.
1. What is the relationship of the adrenal medulla to the
autonomic nervous system?
2. What hormones are secreted by a pheochromocytoma?
3. Why does an elevated urinary level of VMA (a metabolite
of epinephrine and norepinephrine) suggest the presence
of a pheochromocytoma?
4. In view of the pathophysiology of pheochromocytoma,
explain Mrs. Ames’ symptoms, specifically her increased
heart rate, pounding heart, cold hands and feet, visual
disturbances, and nausea and vomiting. What receptors are
involved in each of these symptoms?
5. Why are two values reported for arterial
pressure, and what is the significance of each
value? Why were both the systolic and diastolic
blood pressures elevated?
6. Is there a plausible explanation for the fact that
Mrs. Ames felt hot, even though her hands and
feet were cold?
7. How did phenoxybenzamine lower Mrs. Ames’
blood pressure?
8. After the dosage of phenoxybenzamine was
established, what was the goal of adding a low
dose of propranolol?
9. What might have happened if Mrs. Ames had
been given propranolol alone?