Dr P Muhammed Muneer BHMS,MD(Hom)
The two adrenal glands : each of which weighs about 4 grams – lie at the superior poles of the two kidney.
Each gland is composed of two distinct parts, the adrenal medulla and the adrenal cortex.
The adrenal medulla, the central 20% of the gland is functionally related to the sympathetic nervous system; It secretes the hormones epinephrine and nor epinephrine in response to sympathetic stimulation.
The adrenal cortex secretes cortico steroids hormones. The hormones are all synthesized from the steroid cholesterol.
The Corticosteroids are
1. Mineral corticoids – Especially affect the electrolytes of the extra cellular fluids sodium and potassium.
2. Glucocorticoids – They exhibit important effects that increase blood glucose concentration also effect on both protein and fat metabolism.
Synthesis and secretion of Adreno cortical Hormones
The adrenal cortex has there distinct layers – They are zona glomerulosa, Zona fasciculate and Zona reticularis.
(i) Zona glomerulosa – Constitutes 15% of the adrenal cortex (lies just underneath the capsule)
- Secretes aldosterone (which is the principal mineral corticoid)
- Contain the Enzyme aldosterone syntheses which is necessary for synthesis of aldosterone.
- The secretion of these cells in controlled mainly by the extra cellular fluid concentration of angiotensin II and potassium, both of which stimulate aldosterone secretion.
II. Zona fascicutala :
- Middle and widest layer
- Constitute 75% of adrenal cortex
- Secretes the glucocorticoids cortisol and cortico sterone.
Small amounts of adrenal and conges and estrogens.
- The secretion of these cells is controlled in large part by the hypothalamic – pituitary ancis ulia – adreno corticotropic hormone (ACTH)
III. Zona reticulose
- Deep layer or cortex
- Secretes the adrenal and rogens dehydroepiandro sterone and androstenedione.
- Small amounts of estrogens and gluco corticoids
- ACTH – regulates secretion of these cell
- Cortical and rogen stimulating hormones released from pituitary may also regulate secretion.
Adreno cortical hormones are Steroids Derived from Cholesterol
Although the cells of the adrenal cortex can synthesis small amonts of cholestrol from acetale, approximately 80% of cholestrol used for steroid synthesis is provided by low density liporesteins (LDL) in the circulating plasma.
The important cortico steroid hormones; including synthetic ones, are the following.
1. Aldosterone (very potent, accounts for about 90% or all mineralo corticoid activity)
2. Desoxy cortico sterone (1/30 as potent as aldosterone, but very small quantities secreated)
3. Corticosterone (sught mineralo corticoid activity)
4. 9x – Fluorocortisl (Synthetic, slightly more potent than aldo sterone)
5. Cortisol (Very slight mineral corticoid activity, but large qty secreted)
6. Cortisone (Synthetic, slight mineralo corticoid activity)
1. Cortisol (very potent, accounts for about 95% of all glucocorticoid activity)
2. Cortico sterone (Provides about 4 percent of total gluco corticoid activity, but much less potent than cortisol)
3. Cortisone (Synthetic, almost as potent as cortisol)
4. Prednisonce (Synthetic, four times as potent as cortisol)
5. Methyl prednisone (Synthetic, five times as potent as cortisol)
6. Dexamelthsone (Synthetics, 30 times as potent as cortical)
It is clear from this list that some of these hormones have both glucocortioid and mineralo corticoid activity. It is especially significant that corisol has a small amount of mineralo coticoid activity, because some syndromes of ecers cortisol secretion can cause significant mineral corticoid effects, along with its much more potent gluco corticoid effects.
The intense glucocorticoid activity of the synthetic hormone dexamethasone, which has almost zeor minerl corticoid activity, makes this an especially important drug for stimulating glucocorticoid activity.
The Normal concentration of aldosterone in blood is about 6 nanograms per 100 ml and the secretory rate is 150 to 250 mg / day.
The concentration of cortisol in blood everages 12 mg / 100 ml and the secretary rate averages 15 to 20 mg / day.
Functions of the Mineralo corticoids – Aldosterone
1. Renal and circulatory effects of aldosterone –
Aldosterone increases renal tubular ……….. of sodium and secretion of potassium.
Aldosterone causes sodium to the conserved in the extra cellular fluid while increasing potassium exertion in the urine.
A High concentration of aldosterone in the plasma can transiently decrease the sodium loss into the urine to as little as little as a few mill equivalent day. At the same time potassium loss into urine increases several fold. Therefore, the net effect of excess aldosterone in the plasma is to increase the total quantity of sodium in the extra cellular fluid while decreasing the potassium.
Total loss of adrenal cortical secretion usually causes death with 3 days to 2 weeks unless the person receives extensive salt therapy or injection of mineralo corticoid without mineralo corticoids potassium ion concentration of the extra cellular fluid rises markedly. Sodium and chloride are rapidly lost from the body, and the total extra cellular fluid volume and blood volume become greatly reduced. The person soon develops diminished cardiac output; which progresses to a shockhi… state followed by death. The entire sequence can be previated by the administration of aldosterone or some other mineralo corticoid. Therefore mineralo corticoild … said to be the acute life saving portion of the adreno cortical hormones.
2. Excess aldosterone increases extra cellular fluid volume and arterial pressure.
An aldosterone – mediated increase in extra cellular fluid & volume lasting more than 1 to 2 days also leads to an increase in arterial pressure. The rise in arterial pressure then increases kidney excretion of both salt and wakes called pressure natriuresis and pressure …….. respecting thus after the extra cellular fluid volume increases 5 to 15 percent above normal, arterial pressure aldo increases 15 to 25 mm of Hg and this elevated blood pressure returns the several output of salt and water to normal despite the excess aldosteron. This return to normal of salt and water excretion by the kidneys as a result of pressure …. And ….. is called aldosterone escape.
Conversely when aldosterone secretion become zero large amounts of salt are lost in the urine not only diminishing the amount of sodium chloride in the extra cellular fluid volume the result is severe extra cellular fluid dehydration and low blood volume, leading to circulatory shock. Without therapy this usually causes death within a few days after the adrenal glands suddenly stop secreting aldosterone.
3. Excess aldosterone causes Hypokalemia and muscle weakness; too little aldosterone causes Hyperkalemia and cardiac toxically.
4. Excess aldosterone increases tubular Hydrogen ion secretion with resultant mild alkalosis.
5. Aldosterone stimulates sodium and potassium transport in sweat glands, salway glands, and intestinal epithelial cells.
Aldosterone also greatly enhances sodium absorption by the intestines, especially in the color, while prevent loss of sodium in the stools.
Regulation of Aldosterone secretion
1. Increased potassium ion concentration in the extra cellular fluid greatly increases aldosterone secretion.
2. Increased actively actively of the rennin – angio tension system also greatly increase aldosterone secretion.
3. Increased sodium ion concentration in the extra cellular fluid very slightly decreases aldosterone secretion.
4. ACTH from the anterior pituitary gland is necessary for aldosterone secretion but has little effect in controlling the rate of secretion.
Functions of the Glucocorticoids
Effects or cortisol on carbonytrate metabolis.
Stimulate ….. (Formation of carbohydrate from proteins and some other substances) by the liver often increasing the rate of gluconeogenesis as much as 6 to 10 fold this results mainly from two effect of cortisol.
(i) Cortisol increases the enzyme required to convert aminoacids into glucose in the liver cells.
(ii) Cortisol causes mobilization of aminoacids from the extra hepatic tissues mainly from muscle.
Decreased glucose utilization by the cells
Cortisol also causes a moderate decrease in the rate of glucose utilization by most cells of the body.
A suggested mechanism is based on the observation that glucocorticoids depress the oxidation of incotinamide adenine dinuceleotide (NADH) to form NAD. Because NADH must be oxidized to allow glycolysis this effect could account for the dimmished utilization of glucose by the cells.
Elevaled Blood Glucose concentration and Adrenal Diabetes
Both the increased rate of gluconeogenesis and the moderate reduction in the rate of glucose utilization by the cells cause the bllod glucose concentration to rise the rise blood glucose in turn stimulates secretonsy insulin. The increased plasma levels of insulin, however are not as effective in maintaing plasma glucose as they are under normal conditions.
The increase in blood glucose concentration is occasionally great … (50 percent or more above normal) that the condition is called adrenal diabetes.
Effects of Cortisol on Protein Metabolism
(i) Reduction in cellular protein : Reduction of protein stores is essentially all body cells except those of the liver this is caused by both decreased protein synthesis and increased catabolism of protein already in the cells.
Cortisol also depress the formation of RNA and sub sequent protein synthesis is many extrahepatice tissues especially is musles and lymphoid tissues. In the presence of great excess of cortiol, the muscles can become so weak that the person cannot rise from the squatting position.
i. Cortisol increases liver and plasma protein.
Coincidentially with the reduced proteins elsewhere with body, the liver protein become enhanced further more, the plasma proteins are also increased.
ii. Increased Blood Aminoacids
iii. Diminished transport of aminoacids … extra … cells & enhanced transport .. hepatic cells.
Effects of cortisol on fat metabolism
i) Mobilisation of fatty acids
It promotes mobilization of fatty acids from adipose tissue. This increases the concentration of free fatty acids in the plasma.
The increased mobilization of fats by cortisol, combined with increased oxidation of fatty acids in the cells, helps shift the metabolic system of cells in times of starvation or other stresses from utilization of glucose for energy to utilization of fatty acids. This cortisol mechanism, homener requires several hours to become fully developed.
ii) Obesity caused by excess cortisol: Despite the fact that cortisol can cause a moderate degree of fatty acid mobilization from adipose tissue, many people with excess cortisol secretion develop a peculiar type or obesity with exess deposition of fat in the chest and head regions of the body giving a buffalo like torso and rounded moonface. Althoug the cause in unknown it has been suggested that this obesity results from excess simultaneously food intake, with fat being generated in some tissues of the body more rapidly than it is mobilized & oxidized.
Cortisol is important in resisting stress and inflammation
Almost any type of stress, whether physical or neuogenic, cause an immediate and marked increase in ACTH secretion by the anterioc pilu….. gland followed within minutes by greately increased adreno cortical secretion of cortisol.
Anti……. Effects of cortisol
The administration of large amounts of cortisol can usually block in lamination or even reverse many of its effects once it has begun.
Cortisol causes resolution of inflammation
Regulation of cortisol secretion
ACTH stimulates cortisol secretion
Secretion of cortisol is controlled almost entirely by ACTH secreted by Anterior pituitary gland. This hasmore also called corticotrophin or adreno cartico trop in also enhances the production of adrenal and origins.
ACTH secretion is controlled by corticotrophin releasing factor from hypo thalamus
Physiologic stress increases ACTH and adreno cortial secretion.
Inhibitory effect of cortisol on hypothalamus and on the anterior pitulary to cause decreased ACTH secretion
When ACTH is secreted by the anterior pituitary gland several other hormones that have IIIrd Chemical structure are secreted simultaneously.
Several moderate actine male sex hormones called adrenal and rogens and are continually secreted by the adrenal cortex especially duty fetal life.
Abnormalities of Adrenocortex secretion
Hypoad renalism – Addison’s Disease.
Addissions disease results from failure of adrenal cortices to produce adreno cortial hormones.
Causes I) Primary atrophy of the adrenal cortices.
ii) Tuberculosis destruction of – (cause autoimmunity 80%) the adrenal glands.
iii) Invasion of the adrenal cortices by cancer.
Disturbances in Addisons disease
i) Mineralo corticoid deficiency : Decrease renal tubular sodium reabsorption be lost into urine in great profusion. The net result is greatly decreased extra cellular fluid volume futhere more Hypontremia, Hyperkalemia and mild alkalosis develop.
As the extra cellular fluid becomes depleted, plasma volume falls, RBC concentration rises, cardiac output decreases, and patient dies in shock death usually occurring in the interacted patient 4 days to 2 weeks after cessation of ineralo corticoid secretion.
ii) Gluco corticoid deficiency
Loss of cortisol secretion makes it impossible for a person with addisson’s disease to maintain normal blood glucose concentration between emals because he or she cannot syntheisse significant quantities of glucose by gluconeogensis. Further more lack or cortisol reduces the mobilization of both proteins and fats from the tissue.
Lack of adequate glucorticoid secretion also makes to person with addison’s disease highly susceptible to the deteriorating effects of different types of stress, and even a mild respiratory infection can cause death.
iii. Melanin pigmentation : of the mucous membranes and skin Melanin is not always deposited evenly but occasionally in the thin skin areas, such as the mucous membranes of the lips and the thin skin of the nipples.
An untreated persons with total adrenal destruction dies within a few days to a few weeks because of consuming weakness and usually …… shock. Yet such a person can live for years it small quantities or mineralo corticoids and glucorticoids are administrated daily.
Great quantities or glucocorticoids are occasionally secreted in response to different types of physical or mental stress. In a person with addissons disease, the output of gluco corticoids does not increase during stress. Yet whenever different types of trauma, disease or other stresses, such a surgical operations. Supervence a person in likely to have an acute need for excessive amount of glucocorticoids and often must be given 10 or more times the normal quanitites of glucoroticoids to prevent death.
This critical need for extra gluco corticoids and associated severe debility in times or stresses called an addissonian crisis.
Hyperadrenalism – Cushing’s Syndrome
Causes: 1) Adenomas of anterior pituitary that secrete large amount of ACTH.
2). Abnormal function of the Hypothalamous that causes high levels of or corticotrophin releasing hormones.
3). Ectopic secretion of ACTH by a tumour elsewhere in the body such as an abdominal carcinoma.
4). Adenomas of the adrenal cortex when Cushing syndrome is secondary to excess secretion of ACTH by the anterior pituitary is called cushing’s disease.
5). Cushing syndrome can also occur when large amount of gluco corticoids are administrated over prolonged periods for therapeutic purpose. (for eg RA)
A special characteristic of Cushing syndrome is mobilization of fat from the lower part of the body, with consonants extra depositon of fat in the ….. and upper abdominal regions, giving rising to buffalo torso. The excess secretion of steroid also lead to an edematous appearance of the face, and and rogence potency os some of the hormones sometimes causes acne and hirsutism (excessing growth of facial haia) the appearance of the face in frequently described as moon face”.
Effects of carbohydrate & Protein metabolism
i) Blood glucose concentration – (High as 200 mg/ dl after ….)
ii) Losing protein from muscles in particular causes severe weakness.
iii) Loss of protein synthern in the lymphoid tissue leads to suppressed immune system so many patient dies of infection
Even the protein collagen fibers in the subcutaneous tissue are diminished so that the subcutaneous tissue Teac earily, resulting in development of large purplish striac where they have torn apart in addition severely diminished protein deposition in the bones often causes severe osteoporesis consequent weakness of the bones.
Treatment of cushings syndrome
i) Removing of adrenal hum our.
ii) Hypert….. pitutitary gland or even small tumouss in the pituitary that oversecrete ACTH can sometimes be surgically removed or destroyed by radiation.
If ACTH secretion can not easily be decreased, the only satisfactory treatment is … bilateral partial (or even total) ……….. followed by administration of adrenal steroid to make up for any insufficiency that develops.
Primary Aldosteronism (conn’s syndrome) occasionally a smell tunes of the zone glo… cells occurs and secretes large mounts of alsosterone; the resulting condition is called primary alsosteronism of conn’s syndroeme.
The most important effects are hypokalemine, stright … is ECF volume blood volume, very shaguf increase is plasima sodium… usually not one 4-6 m eq/l increase) and almost always hypertension. Especially inlauesting in primary aldosteronium are occasional period of muscel … caused by hpyothalmous.