Adrenals

The adrenal glands are a pair of endocrine glands that sit atop the kidneys and that release their hormones directly into the bloodstream. The adrenals are flattened, somewhat triangular bodies that, like other endocrine glands, receive a rich blood supply. The phrenic (from the diaphragm) and renal (from the kidney) arteries send many small branches to the adrenals, while a single large adrenal vein drains blood from the gland.

Each adrenal gland is actually two organs in one. The inner portion of the adrenal gland, the adrenal medulla, releases substances called catecholamines, specifically epinephrine, adrenaline, norepinephrine, noradrenaline, and dopamine. The outer portion of the adrenal gland, the adrenal cortex, releases steroids, which are hormones derived from cholesterol.

There are three somewhat distinct zones in the adrenal cortex: the outer part, the zona glomerulosa (15% of cortical mass) made up of whorls of cells; the middle part, the zona fasciculata (50% of cortical mass) made up of columns of cells and that are continuous with the whorls; and an innermost area called the zona reticularis (7% of cortical mass), which is separated from the zona fasciculata by venous sinuses.

The cells of the zona glomerulosa secrete steroid hormones known as mineralocorticoids, which affect the fluid balance in the body, principally aldosterone, while the zona fasiculata and zona reticularis secrete glucocarticoids, notably cortisol and the androgen testosterone, which are involved in carbohydrate, protein, and fat metabolism.

The secretion of the adrenal cortical hormones is controlled by a region of the brain called the hypothalamus, which releases a corticotropin-releasing hormone. This hormone targets the anterior part of the pituitary gland, situated directly below the hypothalamus. The corticotropin-releasing hormone stimulates the release from the anterior pituitary of adreno-corticotropin (ACTH), which, in turn, enters the blood and targets the adrenal cortex. There, it binds to receptors on the surface of the gland's cells and stimulates them to produce the steroid hormones.

Steroids contain as their basic structure three 6-carbon (hexane) rings and a single 5-carbon (pentane) ring. The adrenal steroids have either 19 or 21 carbon atoms. These important hormones are collectively called corticoids. The 21-carbon steroids include glucocorticoids and mineralocorticoids, while the 19-carbon steroids are the androgens. Over 30 steroid hormones are made by the cortex, but only a few are secreted in physiologically significant amounts. These hormones can be classified into three main classes, glucocorticoids, mineralocorticoids, and corticosterone.

Cortisol (hydrocortisone) is the most important glucocorticoid. Its effect is the opposite to that of insulin. It causes the production of the sugar glucose from amino acids and glycogen stored in the liver, called gluconeo-genesis, so increasing blood glucose. Cortisol also decreases the use of glucose in the body (except for the brain, spinal cord, and heart), and it stimulates the use of fatty acids for energy.

Glucocorticoids also have anti-inflammatory and antiallergenic action, so they are often used in the treatment of rheumatoid arthritis. The excessive release of glucocorticoids causes Cushing's disease, which is characterized by fatigue and loss of muscle mass due to the excessive conversion of amino acids into glucose. In addition, there is the redistribution of body fat to the face, causing the condition known as "moon face." The mineralocorticoids are essential for maintaining the balance of sodium in the blood and body tissues and the volume of the extracellular fluid in the body. Aldosterone, the principal mineralocorticoid produced by the zona glomerulosa, enhances the uptake and retention of sodium in cells, as well as the cells' release of potassium. This steroid also causes the tubules of the kidneys to retain sodium, thus maintaining levels of this ion in the blood, while increasing the excretion of potassium into the urine. Simultaneously, aldosterone increases reabsorption of bicarbonate by the kidney, thereby decreasing the acidity of body fluids.

A deficiency of adrenal cortical hormone secretion causes Addison's disease, characterized by fatigue, weakness, skin pigmentation, a craving for salt, extreme sensitivity to stress, and increased vulnerability to infection.

The adrenal androgens are weaker than testosterone, the male hormone produced by the testes. However, some of these androgens, including androstenedione, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate can be converted by other tissues to stronger androgens, such as testosterone. The cortical output of androgens increases dramatically after puberty, giving the adrenal gland a major role in the developmental changes in both sexes. The cortex also secretes insignificant amounts of estrogen.

The steroid hormones are bound to steroid-binding proteins in the bloodstream, from which they are released at the surface of target cells. From there they move into the nucleus of the cell, where they may either stimulate or inhibit gene activity.

The release of the cortical hormones is controlled by adrenocorticotropic (ACTH) from the anterior pituitary gland. The level of ACTH has a diurnal periodicity, that is, it undergoes a regular, periodic change during the 24-hour time period. ACTH concentration in the blood rises in the early morning, peaks just before awaking, and reaches its lowest level shortly before sleep.

Several factors control the release of ACTH from the pituitary, including corticotropin-releasing hormone from the hypothalamus, free cortisol concentration in the plasma, stress (e.g., surgery, hypoglycemia, exercise, emotional trauma), and the sleep-wake cycle.

Mineralocorticoid release is also influenced by factors circulating in the blood. The most important of these factors is angiotensin II, the end-product of a series of steps starting in the kidney. When the body's blood pressure declines, this change is sensed by a special structure in the kidney called the juxtaglomerular apparatus. In response to this decreased pressure in kidney arterioles the juxtaglomerular apparatus releases an enzyme called renin into the kidney's blood vessels. There, the renin is converted to angiotensin I, which undergoes a further enzymatic change in the bloodstream outside the kidney to angiotensin II. Angiotensin II stimulates the adrenal cortex to release aldosterone, which causes the kidney to retain sodium. The increased concentration of sodium in the blood-filtering tubules of the kidney causes an osmotic movement of water into the blood, thereby increasing the blood pressure.

The adrenal medulla, which makes up 28% of the mass of the adrenal glands, is composed of irregular strands and masses of cells that are separated by venous sinuses. These cells contain many dense vesicles, which contain granules of catecholamines.

The cells of the medulla are modified ganglion (nerve) cells that are in contact with preganglionic fibers of the sympathetic nervous system. There are two types of medullary secretory cells, called chromaffin cells: the epinephrine (adrenalin)-secreting cells, which have large, less dense granules, and the norepinephrine (noradrenalin)-secreting cells, which contain smaller, very dense granules that do not fill their vesicles. Most chromaffin cells are the epinephrine-secreting type. These substances are released following stimulation by the acetylcholine-releasing sympathetic nerves that form synapses on the cells. Dopamine, a neurotransmitter, is secreted by a third type of adrenal medullar cell, different from those that secrete the other amines.

The extensive nerve connections of the medulla essentially mean that this part of the adrenal gland is a sympathetic ganglion, that is, a collection of sympathetic nerve cell bodies located outside the central nervous system. Unlike normal nerve cells, the cells of the medulla lack axons and instead, have become secretory cells.

The catecholamines released by the medulla include epinephrine, norepinephrine and dopamine. While not essential to life, they help to prepare the body to respond to short-lived but intense emergencies.

Most of the catecholamine output in the adrenal vein is epinephrine. Epinephrine stimulates the nervous system and also stimulates glycogenolysis (the breakdown of glycogen to glucose) in the liver and in skeletal muscle. The free glucose is used for energy production or to maintain the level of glucose in the blood. In addition, it stimulates lipolysis (the breakdown of fats to release energy-rich free fatty acids) and stimulates metabolism in general. Epinephrine also increases the force and rate of heart muscle contraction, which results in an increase in cardiac output.

The only significant disease associated with the adrenal medulla is pheochromocytoma. This tumor is highly vascular and secretes its hormones in large amounts. The symptoms of this disease include hypertension, sweating, headaches, excessive metabolism, inflammation of the heart, and palpitations.