Download Adrenal Glands

Adrenal Glands
Lecture: 4
Dr. Saif Saadedeen
For the body to function properly, its various parts and organs must communicate
with each other to ensure that a constant internal environment (homeostasis) is
maintained. Two systems help ensure communication: the nervous system and the
hormonal system; neuroendocrine system. The nervous system generally allows
rapid transmission of information between different body regions. Conversely,
hormonal communication, is better suited for longer lasting regulatory actions. Thus,
the two communication systems complement each other.
Endocrine Glands
Including the hypothalamus, pituitary gland, adrenal glands, gonads, (testes and
ovaries), thyroid gland, parathyroid glands, and pancreas.
What Are Hormones?
Hormones are molecules that are produced by endocrine glands. The term
“endocrine” implies that in response to specific stimuli, the products of those glands
are released into the bloodstream. The hormones then are carried via the blood to
their target cells. The target cells for each hormone are “receptors” that are located
either on the cell surface or inside the cell. The interaction between the hormone and
its receptor triggers a cascade of biochemical reactions in the target cell that
eventually modify the cell’s function or activity.
Conversely, exocrine glands (e.g., sweat glands and salivary glands) release their
secretions to the outside of the body (e.g., sweat) or into a hollow space that is open
to the outside (e.g., saliva released into the mouth).
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Mechanism of Action
The neuroendocrine system is a highly complex and tightly controlled network of
hormones released by endocrine glands throughout the body. Several classes of
hormones exist, including steroids, amino acid derivatives, polypeptides and
proteins. Those hormone classes differ in their general molecular structures. As a
result of the structural differences, their mechanisms of action also differ. Steroids
and amino acid derivatives can enter the cell, while because of their chemical
structure, the polypeptide and protein hormones cannot enter cells; instead, they
interact with receptors on the cell surface.
The Adrenal Glands
The adrenal glands are small structures located on top of the kidneys.
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Structurally, they consist of an outer layer (the cortex) and an inner layer (the
medulla). The cortex is about 90 % of the gland and it is consist of three layers: zona
Glomerulosa (outer), zona Fasciculate (middle) and zona Reticularis (inner).
 Zona Glomerulosa secretes Mineralcorticoids mainly aldosterone
 Zona Fasciculata secretes Glucocorticoids mainly cortisol
 Zona Reticularis secretes Androgens mainly testosterone
The sex hormones produced by the cortex are insignificant compared with the
amounts normally produced by the ovaries and testes. The adrenal medulla generates
two substances; adrenaline and noradrenaline (epinephrine and norepinephrine)
that are released as part of the fight-or-flight response to various stress factors.
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Mineralocorticoids:
Aldosterone which regulates physiologic levels of sodium and potassium is the
most important mineralocorticoid. It binds to renal mineralocorticoid receptors,
causing sodium retention and increased excretion of potassium. In contrast to the
glucocorticoids; pituitary or hypothalamic hormones do not regulate aldosterone
release. Instead, it is controlled primarily by another hormone system, the reninangiotensin system.
Glucocorticoids:
Cortisol is the major glucocorticoid in humans. Levels are highest in the morning
and lowest in the middle of the night. Cortisol helps control carbohydrate, protein,
and lipid metabolism. For example, cortisol increases glucose levels in the blood by
stimulating gluconeogenesis and promotes the formation of glycogen (a molecule
that serves as the storage form of glucose) in the liver.
In addition to those metabolic activities, cortisol appears to protect the body
against the deleterious effects of various stress factors, including acute trauma, major
surgery, severe infections, pain, blood loss, hypoglycemia, and emotional stress. All
of these stress factors lead to drastic increases in the cortisol levels in the blood.
For people in whom cortisol levels cannot increase (e.g., because they had their
adrenal glands removed), even mild stress can be fatal. High doses of cortisol and
other corticosteroids can be used medically to suppress tissue inflammation in
response to injuries and to reduce the immune response to foreign molecules.
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Adrenal androgens: mainly the testosterone. They are probably important in the
initiation of puberty.
Catecholamines:
In humans, most circulating noradrenaline (norepinephrine) is derived from
sympathetic nerve endings. However, noradrenaline is converted to adrenaline
(epinephrine) in the adrenal medulla. The medulla is thus the major source of
circulating adrenaline.
 Local anesthesia with 1:100,000 epinephrine contains 0.01 mg/ml epinephrine
…one carpule of 1.8 ml contains 0.18 mg.
 In patients with hypertension, local anesthetics without vasoconstrictors may
be used as needed. If a vasoconstrictor is necessary in hypertensive patients
(with blood pressure <180/110 mm Hg) can safely be given up to 0.036 mg
epinephrine (two cartridges containing 1:100,000 epinephrine) at one
appointment (the benefits of its use far outweighing any potential problems);
intravascular injections are to be avoided.
 An additional concern with patients with hypertension is the potential for
adverse drug interactions between epinephrine (α and β agonist) and
antihypertensive drugs specifically β-blockers (e.g., propranolol), but such
interaction is dose-dependent and very unlikely to occur at the usual doses.
Phenylephrine is a selective agonist of the α receptor.
Hormone Systems
Some hormones are controlled directly by the metabolic pathways that they
influence. For example, blood sugar levels directly control insulin and glucagon
release by the pancreas. Conversely, many hormones produced by target glands are
regulated by pituitary hormones, which in turn are controlled by hypothalamic
hormones. Examples of such regulatory hormonal cascades include the
hypothalamic-pituitary-adrenal (HPA) axis.
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The HPA Axis
Activation of the HPA axis, is initiated with the release of CRH (Corticotropin
Releasing Hormone) from the hypothalamus. This release occurs in response to
various stimuli, including almost any type of physical or psychological stress. CRH
then stimulates the anterior pituitary to produce ACTH (Adrenocorticotropic
Hormone). ACTH, in turn, activates adrenal hormone production.
The activity of the HPA axis is regulated by negative feedback mechanisms.
Thus, increased cortisol levels repress CRH release by the hypothalamus and ACTH
release by the pituitary.
Any disturbances in the HPA axis can result in serious medical consequences. For
example, insufficient hormone production by the adrenal cortex causes Addison’s
disease. Equally deleterious is the excessive glucocorticoid production that results
from excess ACTH release (Cushing’s syndrome). Both acute and chronic alcohol
consumption have been shown to activate the HPA axis, and some drinkers develop
a so-called pseudo-Cushing’s syndrome.
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Therapeutic use of glucocorticoids
Equivalent doses of 5 mg prednisolone are:
● Hydrocortisone 20 mg.
● Dexamethasone 0.5 mg.
 Short-Acting (<12 Hours): Hydrocortisone
 Intermediate-Acting (12-36 Hours): Prednisolone and Triamcinolone
 Long-Acting (>36 Hours): Betamethasone and Dexamethasone
 Inhaled: Beclomethasone
Adverse effects of glucocorticoids
The clinical features of glucocorticoid excess are related to dose and duration of
therapy.
 Diabetes mellitus can be worsened.
 Mood disturbance, either depression or mania, and insomnia.
 Fracture risk is greater in glucocorticoid-induced osteoporosis than in postmenopausal osteoporosis, so when systemic glucocorticoids are prescribed for
> 3 months, bone-protective therapy should be considered.
 The patient may show no febrile response to an infection.
 Glucocorticoids act synergistically with NSAIDs, including aspirin, to
increase the risk of gastric erosions and ulceration.
 Latent TB may be re-activated and patients on corticosteroids should be
advised to avoid contact with varicella zoster virus if they are not immune.
Management of glucocorticoid withdrawal
All glucocorticoid therapy can suppress the HPA axis; however, a crisis due to
adrenal insufficiency on withdrawal of glucocorticoids occurs only after prolonged
(> 3 weeks) or repeated courses, or doses of prednisolone > 7.5 mg/day. In these
circumstances, steroid withdrawal must be slow (tapering) as the HPA axis may
take months to recover. Patients must avoid sudden withdrawal.
The end of Part 1…..
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