The adrenal gland is two glands in one

An adrenal gland sits above each kidney, just below the middle of your
back.
Functionally and anatomically, each adrenal gland consists of a gland
within a gland.
The adrenal cortex + adrenal medulla are structurally and functionally
different.
The core, called the
adrenal
medulla, 2014
produces the hormone
shivani
g varmani,
epinephrine (also known as adrenaline) and, to a lesser degree,
norepinephrine (or noradrenaline), which also acts as a
neurotransmitter in the nervous system .
The medulla develops from nervous tissue and is under the control of
the nervous system
Surrounding the medulla is the adrenal cortex, which produces other
hormones. The cortex is under hormonal control, largely by
adrenocorticotropin (ACTH) from the anterior pituitary

The cortex consists of three zones: an outer zona glomerulosa, a middle

zona fasciculata, and an inner zona reticularis. These zones are believed
to have different functions.

DR. SHIVANI G. VARMANI, 2014

shivani g varmani, 2014

Functions of the Adrenal Cortex
The adrenal cortex use cholesterol to secrete three classes of steroid
hormones called corticosteroids, or corticoids, for short. There are three
functional categories of corticosteroids:
(1) mineralocorticoids, which regulate Na + and K + balance;
(2) glucocorticoids, which regulate the metabolism of glucose and other
organic molecules;
(3) sex steroids, which are weak androgens (including
dehydroepiandrosterone, or DHEA ) that supplement the sex steroids
secreted by the gonads.
The biosynthetic pathways from cholesterol diverge in the different
zones of the adrenal cortex, so that a particular category of
corticosteroid is produced in a particular zone of the adrenal cortex ( fig.
11.19 ).

DR. SHIVANI G. VARMANI, 2014

shivani g varmani, 2014

Aldosterone is the
most
potent
mineralocorticoid.
The
mineralocorticoids are produced in the zona glomerulosa and stimulate
the kidneys to retain Na + and water while excreting K + in the urine.
These actions help to increase the blood volume and pressure, and to
regulate blood electrolyte balance. If the adrenal glands are removed
from an animal, it must have sodium added to its diet, or its sodium will
be depleted and it will die.
The predominant glucocorticoid in humans is cortisol (hydrocortisone ),
which is critical for mediating the bodys response to stress. The
secretion of cortisol is stimulated by ACTH from the anterior pituitary (
fig. 11.20 ). The immediate reaction to a frightening situation is
stimulated by your nervous system and by the release of epinephrine.
This fight-or-flight response ensures that your muscles will have enough
oxygen and glucose to fuel your escape. You have a limited amount of
blood glucose, however, and you need to conserve it for your muscles
and your brain.
Within minutes of the frightening stimulus, your blood cortisol level
rises. Cortisol and other glucocorticoids have many effects on
metabolism; they stimulate gluconeogenesis ( production of glucose
from amino acids and lactic acid) and inhibit glucose utilization, which
help to raise the blood glucose level; and they promote lipolysis
(breakdown of fat) and the consequent release of free fatty acids into
the blood.

DR. SHIVANI G. VARMANI, 2014

 This is not a time to feel sick, have allergic reactions, or heal wounds, so
cortisol also blocks immune system reactions. That is why Exogenous
glucocorticoids (taken as pills, injections, sprays, and topical creams
having prednisone) are used medically to suppress the immune response
and inhibit inflammation. Thus, these drugs are very useful in treating
inflammatory diseases such as asthma and rheumatoid arthritis.
As might be predicted based on their metabolic actions, the side effects
of glucocorticoids include hyperglycemia (Adrenal diabetes) and
decreased glucose tolerance. Other negative side effects include
decreased synthesis of collagen and other extracellular matrix proteins

shivani g varmani, 2014

DR. SHIVANI G. VARMANI, 2014

shivani g varmani, 2014

CLINICAL APPLICATION
An excessively high level of corticosteroids in the blood causes Cushings
syndrome. This may result from the oversecretion of ACTH (usually by a tumor
of the anterior pituitary) that overly stimulates the adrenal cortex to secrete
corticosteroids, but it can also be produced by a tumor of the adrenal cortex
that secretes excessive amounts of corticosteroids. Cushings syndrome is
characterized by changes in carbohydrate and protein metabolism,
hyperglycemia, hypertension, and muscular weakness. Metabolic problems
give the body a puffy appearance and can cause structural changes
characterized as buffalo hump and moon face.
Addisons disease is caused by inadequate secretion of both glucocorticoids
and mineralocorticoids, which results in hypoglycemia, sodium and potassium
imbalance, dehydration, hypotension, rapid weight loss, and generalized
weakness. A person with this condition who is not treated with corticosteroids
will eventually die because of severe electrolyte imbalance and dehydration.
President John F. Kennedy had Addisons disease, but few knew of it because it

DR. SHIVANI G. VARMANI, 2014

was well controlled by corticosteroids. In the original description of the disease

by Addison (17931860), he described a characteristic discoloration of the
skin . . . smoky appearance, or various tints or shades of deep amber or
chestnut brown. This is caused by the very high secretion of ACTH, which at
that concentration can stimulate melanocytes. High ACTH secretion results
from inadequate negative feedback (due to low glucocorticoid secretion).
Functions of the Adrenal Medulla

shivani g varmani, 2014

The cells of the adrenal medulla secrete epinephrine and norepinephrine in an

approximate ratio of 4 to 1. The effects of these catecholamine hormones are
similar to those caused by stimulation of the sympathetic nervous system,
except that the hormonal effect lasts about 10 times longer. The hormones
from the adrenal medulla increase the cardiac output and heart rate, dilate
coronary blood vessels, increase mental alertness, increase the respiratory
rate, and elevate the metabolic rate.
Epinephrine and norepinephrine are both amine hormones derived from the
amino acid tyrosine. They are water- soluble, and they both bind to the same
receptors on the surfaces of target cells. These receptors can be grouped into
two general types, -adrenergic and -adrenergic receptors, which stimulate
different actions within cells. Epinephrine acts equally on both types, but
norepinephrine acts mostly on -adrenergic receptors. Therefore, drugs called
beta blockers, which selectively block -adrenergic receptors, can reduce the
fight-or-flight responses to epinephrine without disrupting the physiological
regulatory functions of norepinephrine. Beta blockers are commonly
prescribed to reduce anxiety, such as that brought on by public speaking.

shivani g varmani, 2014

CLINICAL APPLICATION
A tumor of the adrenal medulla is referred to as a pheochromocytoma. This
tumor causes hypersecretion of epinephrine and norepinephrine, which
produces an effect similar to continuous sympathetic nerve stimulation. The
symptoms of this condition are hypertension, elevated metabolism,
hyperglycemia and sugar in the urine, nervousness, digestive problems, and
sweating. It does not take long for the body to become totally fatigued under
these conditions, making the patient susceptible to other diseases

DR. SHIVANI G. VARMANI, 2014

Stress and the Adrenal Gland

In 1936 a Canadian physiologist, Hans Selye, discovered that injections of a
cattle ovary extract into rats (1) stimulated growth of the adrenal cortex; (2)
caused atrophy of the lymphoid tissue of the spleen, lymph nodes, and
thymus; and (3) produced bleeding peptic ulcers.
At first he attributed these effects to the action of a specific hormone in the
extract. However, subsequent experiments revealed that injections of a variety
of substancesincluding foreign chemicals such as formaldehydecould
produce the same effects. Indeed, the same pattern occurred when Selye
subjected rats to cold environments or when he dropped them into water and
made them swim until they were exhausted. The specific pattern of effects
produced by these procedures suggested that the effects were due to
something the procedures shared in common.

shivani g varmani, 2014

Selye reasoned that all of the procedures were stressful, and that the pattern
of changes he observed represented a specific response to any stressful agent.
He later discovered that these effects were produced by activation of the
pituitary-adrenal axis. Under stressful conditions, there is increased secretion
of ACTH from the anterior pituitary, and thus there is increased secretion of
glucocorticoids from the adrenal cortex. On this basis, Selye stated that there is
a nonspecific response of the body to readjust itself following any demand
made upon it. Stress causes a rise in the plasma glucocorticoid levels. Selye
termed this nonspecific response the general adaptation syndrome

(GAS). Stress, in other words, produces GAS. There are three stages in the
response to stress: (1) the alarm reaction, when the adrenal glands are
activated; (2) the stage of resistance, in which readjustment occurs; and (3) if
the readjustment is not complete, the stage of exhaustion, which may lead to
sickness and possibly death.
For example, when a person suffers from the stress of severe infections,
trauma, burns, and surgery, the cortisol level can rise in proportion to the
severity of the stress to as high as six times basal levels. There is evidence that
this response of the pituitary-adrenal axis is needed for proper recovery from
the illness or trauma, perhaps because cortisol and other glucocorticoids
inhibit the immune response, thereby reducing damage due to inflammation.

DR. SHIVANI G. VARMANI, 2014

Thus, severe infections and trauma that trigger an immune response also
activate mechanisms (the adrenals secretion of cortisol) to limit that immune
response. Indeed, patients who cannot secrete an adequate amount of cortisol
for different reasons have an increased risk of death during an illness or
trauma.
shivani g varmani, 2014
The sympathoadrenal system becomes activated, with increased secretion of
epinephrine and norepinephrine, in response to stressors that challenge the
organism to respond physically. This is the fight-or-flight reaction different
emotions, however, are accompanied by different endocrine responses. More
modern stress theories regard stressors as stimuli that disrupt homeostasis,
and that evoke particular neuroendocrine responses that can vary depending
on the nature of the stressors. The different responses of the pituitary-adrenal
axis and sympathoadrenal system to different stressors are coordinated by
higher brain regions. The hypothalamus-anterior pituitary-adrenal axis, with
rising levels of glucocorticoids, becomes more active when the stress is of a
chronic nature and when the person is more passive and feels less in control.
Because glucocorticoids suppress the immune system, it is reasonable to
expect that chronic stress may lead to an increased risk of illness. Indeed, there
does appear to be an association between chronic stress and susceptibility to
disease. Some scientists believe that high cortisol and/or high CRH may act on
the brain in chronic stress to contribute to anxiety and depression.
Glucocorticoids stimulate catabolism, chiefly the breakdown of muscle protein
and fat. At the same time, they stimulate the liver to convert amino acids to
glucose (in a process termed gluconeogenesis), leading to a rise in blood
glucose concentration. Through these and other effects, the glucocorticoids
antagonize the actions of anabolic hormones, including growth hormone and
shivani g varmani, 2014
insulin.
Chronic stress, with its prolonged high secretion of glucocorticoids, can
thereby aggravate insulin resistance the reduced sensitivity of target tissues
to insulin. Stress can thus make treatment of diabetes difficult, and can
contribute to a constellation of symptoms associated with type 2 diabetes
mellitus. Diabetes, and the metabolic syndrome associated with it. Because
glucocorticoids such as hydrocortisone (cortisol) can inhibit the immune
system and suppress inflammation, exogenous glucocorticoidsincluding
DR. SHIVANI G. VARMANI, 2014

prednisolone and dexamethasone are medically very useful. They are given
as pills or injections to treat various inflammatory conditions and to suppress
the immune rejection of transplanted organs. However, as expected from the
principles of negative feedback, exogenous glucocorticoids suppress the
secretion of ACTH from the anterior pituitary, and thus the secretion of
endogenous hydrocortisone from the adrenal cortex. Suppression of ACTH
secretion can lead to atrophy of the adrenal cortex that may persist for months
after the treatment with exogenous glucocorticoids.

shivani g varmani, 2014

DR. SHIVANI G. VARMANI, 2014