Adrenal glands

There are two adrenal glands, one located on top of each kidney. These glands are composed of two distinct functional regions:

• Adrenal medulla

• Adrenal cortex

Adrenal medulla. Derived from neural crest tissue, the adrenal medulla forms the inner portion of the adrenal gland. It is the site of production of the catecholamines, epinephrine and norepinephrine, which serve as a circulating counterpart to the sympathetic neurotransmitter, norepinephrine, released directly from sympathetic neurons to the tissues. As such, the adrenal medulla and its hormonal products play an important role in the activity of the sympathetic nervous system. This is fully discussed in Chapter 9, which deals with the autonomic nervous system.

Adrenal cortex. The adrenal cortex forms the outer portion of the adrenal gland and accounts for 80 to 90% of the weight of the gland. It is the site of synthesis of many types of steroid hormones such as:

• Mineralocorticoids

• Glucocorticoids

• Adrenal androgens

Mineralocorticoids. The primary mineralocorticoid is aldosterone. The actions of this hormone include:

• Stimulation of renal retention of sodium

• Promotion of renal excretion of potassium

Aldosterone acts on the distal tubule of the nephron to increase sodium reabsorption. The mechanism of action involves an increase in the number of sodium-permeable channels on the luminal surface of the distal tubule and an increase in the activity of the Na+-K+ ATPase pump on the basilar surface of the tubule. Sodium diffuses down its concentration gradient out of the lumen and into the tubular cells. The pump then actively removes the sodium from cells of the distal tubule and into the extracellular fluid so that it may diffuse into the surrounding capillaries and return to the circulation. Due to its osmotic effects, the retention of sodium is accompanied by the retention of water. In other words, wherever sodium goes, water follows. As a result, aldosterone is very important in regulation of blood volume and blood pressure. The retention of sodium and water expands the blood volume and, consequently, increases mean arterial pressure.

The retention of sodium is coupled to the excretion of potassium. For every three Na+ ions reabsorbed, two K+ ions and one H+ ion are excreted.

The release of aldosterone from the adrenal cortex is regulated by two important factors:

• Serum potassium levels

• The renin-angiotensin system

The mechanism by which potassium regulates aldosterone secretion is unclear; however, this ion appears to have a direct effect on the adrenal cortex. An increase in the level of potassium in the blood stimulates the release of aldosterone. The effect of aldosterone on the kidney then decreases the level of potassium back to normal.

Angiotensin II (Ag II) is a potent stimulus for the secretion of aldosterone. The formation of Ag II occurs by the following process:

Angiotensinogen 0 renin Angiotensin I

0 ACE Angiotensin II

This multistep process is initiated by the enzyme renin. Angiotensinogen is a precursor peptide molecule released into the circulation from the liver.

In the presence of renin, an enzyme produced by specialized cells in the kidney, angiotensinogen is split to form angiotensin I. This prohormone is then acted upon by angiotensin-converting enzyme (ACE) as the blood passes through the lungs to form Ag II. Angiotensin II acts directly on the adrenal cortex to promote aldosterone secretion.

Because this process requires renin in order to occur, it is important to understand the factors involved in its release from the kidney. These factors include:

• Decrease in blood volume

• Decrease in blood pressure

• Sympathetic stimulation

A decrease in blood volume or blood pressure may result in a decrease in the blood flow to the kidney. The kidney monitors renal blood flow by way of stretch receptors in the vessel walls. A decrease in renal blood flow stimulates the release of renin. The subsequent secretion of aldosterone causes retention of sodium and water and, therefore, an increase in blood volume and blood pressure back to normal. An increase in renal blood flow tends to cause the opposite effect.

Sympathetic nerve activity causes an increase in blood pressure through many mechanisms, including an increase in cardiac activity and vasoconstriction. Activation of the sympathetic system also causes the stimulation of Pj-adrenergic receptors on the renin-producing cells, which promotes renin release.

Glucocorticoids. The primary glucocorticoid is cortisol. Receptors for the glucocorticoids are found in all tissues. The overall effects of these hormones include:

• Increase in blood glucose

• Increase in blood free fatty acids

Cortisol increases blood glucose by several mechanisms of action including:

• Decrease in glucose utilization by many peripheral tissues (especially muscle and adipose tissue)

• Increase in availability of gluconeogenic substrates

• Increase in protein catabolism (especially muscle)

• Increase in lipolysis

• Increase in hepatic gluconeogenesis

Cortisol-induced lipolysis not only provides substrates for gluconeogenesis (formation of glucose from noncarbohydrate sources) but it also increases the amount of free fatty acids in the blood. As a result, the fatty acids are used by muscle as a source of energy and glucose is spared for the brain to use to form energy.

The release of cortisol from the adrenal cortex is regulated by several factors including:

• Circadian rhythm

• Negative-feedback inhibition by cortisol

Corticotropin-releasing hormone (CRH) secreted from the hypothalamus stimulates the release of ACTH from the adenohypophysis. This pituitary hormone then stimulates the release of cortisol from the adrenal cortex. The hormones of this hypothalamic-pituitary-adrenocortical axis exhibit marked diurnal variation. This variation is due to the diurnal secretion of CRH. The resulting secretion of ACTH increases at night and peaks in the early morning just before rising (4 a.m. to 8 a.m.). The levels of ACTH then gradually fall during the day to a low point late in the evening, between 12 p.m. and 4 p.m. This rhythm is influenced by many factors, including light-dark patterns, sleep-wake patterns, and eating. After an individual changes time zones, it takes about 2 weeks for this rhythm to adjust to the new time schedule; this may account for some aspects of jet lag.

Cortisol is an important component of the body's response to physical and psychological stress. Nervous signals regarding stress are transmitted to the hypothalamus and the release of CRH is stimulated. The resulting increase in cortisol increases levels of glucose, free fatty acids, and amino acids in the blood, providing the metabolic fuels that enable the individual to cope with the stress. A potent inhibitor of this system is cortisol itself. This hormone exerts a negative-feedback effect on the hypothalamus and the adenohypo-physis and inhibits the secretion of CRH and ACTH, respectively.

Pharmacy application: therapeutic effects of corticosteroids

When administered in pharmacological concentrations (greater than physiological), cortisol and its synthetic analogs (hydrocortisone, prednisone) have potent anti-inflammatory and immunosuppressive effects. In fact, these steroids inhibit almost every step of the inflammatory response resulting in the decreased release of vasoactive and chemoattractive factors, decreased secretion of lipolytic and proteolytic enzymes, decreased extravasation of leukocytes to areas of injury, and, ultimately, decreased fibrosis. Typically, the inflammatory response is quite beneficial in that it limits the spread of infection. However, in many clinical conditions, such as rheumatoid arthritis and asthma, the response becomes a destructive process. Therefore, although glucocorticoids have no effect on the underlying cause of disease, the suppression of inflammation by these agents is very important clinically.

Corticosteroids also exert inhibitory effects on the overall immune process. These drugs impair the function of the leukocytes responsible for antibody production and destruction of foreign cells. As a result, corticosteroids are also used therapeutically in the prevention of organ transplant rejection.

Adrenal androgens. The predominant androgens produced by the adrenal cortex are dehydroepiandrosterone (DHEA) and androstenedione. These steroid hormones are weak androgens; however, in peripheral tissues they can be converted to more powerful androgens, such as testosterone, or even to estrogens. The quantities of these hormones released from the adrenal cortex are very small. Therefore, the contribution of this source of these hormones to androgenic effects in the male is negligible compared to that of the testic-ular androgens. However, the adrenal gland is the major source of androgens in females. These hormones stimulate pubic and axillary (underarm) hair development in pubertal females. In pathological conditions in which adrenal androgens are overproduced, masculinization of females may occur.

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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