1. PHYSIOLOGY OF THE ENDOCRINE SYSTEM
Dr. Sajeda Al-Chalabi
Assist.Proff/Dept .of Physiology

2. Adrenal Gland
The two adrenal glands , each of which weighs 4 gm , lie at the superior poles of the kidneys

3. The Adrenal Gland
Figure 18.16

4. Each gland is composed of 2 parts , the adrenal medulla and adrenal cortex. The adrenal medulla ,central 20% of the gland , is functionally related to the sympathetic nervous system , it secrets the hormones epinephrine & norepinephrine in response to sympathetic stimulation . In turn these hormones cause almost the same effect as direct stimulation of the sympathetic nerves in all parts of the body . The adrenal cortex secretes corticoids . These hormones synthesized from the steroid cholesterol ,and they all have the similar chemical formulas .

5. The corticoids , mineralocorticoids ,glucocorticoids and androgens
Two major types of adrenocortical hormones , the mineralocorticoids & the glucocorticoids, are secreted by the adrenal cortex . In addition small amount of hormones are secreted , especially androgenic hormones which have the same effect of testosterone ( male sex hormone ) . Mineralocorticoids affect the electrolytes ( minerals ) of the ECF , sodium & potassium . Glucocorticoids they increase blood glucose concentration . The steroids include aldosterone & cortisols which are the principal glucocorticoids .

6. Synthesis and secretion of the adrenocortical hormones
The adrenal cortex has 3 distinct layers .

7. Zona glomerulosa: Zona fasiculata :
a thin layer of cells that lies just underneath the capsule , constitutes about 15% of the adrenal cortex . These cells secrete aldosterone because they contain the enzyme aldosterone synthase . The secretion of these cells is controlled by the ECF concentration of angiotensin II & potassium , both of which stimulates aldosterone secretion .
Zona fasiculata :
the middle and widest layer , constitutes about 75% of the adrenal cortex and secretes the glucocorticoids , cortisole and corticosterone as well as small amounts of androgens and estrogens . The secretion of these cells is controlled by the hypothalamic – pituitary axis via ACTH .

8. Zona reticularis :
the deep layer of the cortex , secretes the adrenal androgens dehydroepiandrosterone (DHEA) and androstenedione , as well as small amounts of estrogens and some glucocorticoids. ACTH also regulates secretion of these cells .

9. Mineralocorticoids include :
Aldosterone (very potent account for 90 % of all mineralocorticoids activity).
Deoxycorticosterone (1 / 30 as a potent as aldosterone , but very small quantities secreted).
Corticosterone ( slight mineralocorticoid activity )
9 - Fluocorisol ( Synthetic, slightly more potent than aldosterone ) .
Cortisol ( very slight mineralocorticoid activity, but large quantity secreted ).
Cortisone ( Synthetic, slight mineralocorticoid activity ) .

10. Glucocorticoids :
Cortisol ( very potent, account for about 95% of all glucocorticoids activity ).
Corticosterone ( provides about 4% of total glucocorticoids activity, but much less potent than cortisol ).
Cortisone ( synthetic, almost as potent as cortisol ).
Prednisone (synthetic, four times as potent as cortisol).
Methyl prednisone ( synthetic, five times as potent as cortisol)
Dexamethasone ( synthetic, 30 times as potent as cortisol ).
Approximately 90-95% of cortisol in the plasma binds to plasma proteins , especially globulin called cortisol-binding globulin or transcortin & to a lesser extent to albumin .
Cortisol has half life of minutes .
Only about 60% of the circulating aldosterone combinds with the plasma proteins, so about 40% in the free form . Aldosterone has short half life of about 20 minutes .

11. Aldosterone’s mineralocorticoid activity is about 3000 times greater than that
of cortisol, but the plasma concentration of cortisol is nearly 2000 times that of aldosteroneThe concentration of aldosterone in blood is about 6nanograms/100 ml .
The concentration of cortisol in the blood averages 12 mg /100 ml.
Functions of the mineralocorticoids – aldosterone
Renal & circulatory effects of aldosterone :
Aldosterone increases absorption of sodium and secretion of potassium by the renal tubular epithelial cells especially in the principal cells of the collecting tubule and to a lesser extent in the distal tubules and the collecting ducts. Therefore, aldosterone causes sodium to be conserved in the ECF while increasing potassium excretion in the urine .
Excess aldosterone increases ECF volume and arterial pressure but has only small effect on the plasma sodium concentration, although, has a potent effect in decreasing the rate of sodium excretion by the kidneys, the concentration of sodium in the extra cellular fluids often rises only a few milliequievelants.

12. The reason for this is that when sodium is reabsorbed , there is simultaneous osmotic absorption of almost equivalent amount of water also small increase in ECF sodium concentration stimulate thirst and increased water intake . Therefore the ECF volume , increases almost as much as the retained sodium , but without much change in sodium concentration . An aldosterone – mediated increase in ECF volume last for 1-2 days also leads to an increase in arterial pressure , this increases kidney excretion of both salt and water called pressure natriuresis and pressure diuresis . This return to normal of salt and water excretion by the kidneys as a result of pressure diuresis and natriuresis is called aldosterone escape . Conversely , when aldosterone secretion becomes zero , large amounts of salt are lost in the urine , decreasing the ECF volume , the result is circulatory shock .

13. 3. Excess aldosterone causes hypokalemia and muscle weakness
3. Excess aldosterone causes hypokalemia and muscle weakness . Too little aldosterone causes hyperkalemia and cardiac toxicity . Excess secretion of aldosterone causes serious decrease in plasma potassium concentration , sometimes from the normal value of 4.5 mg / L to as low as 2 mg / L this condition is called hypokalemia . When potassium ion concentration falls below about ½ normal severe muscle weakness often develops . Conversely , when aldosterone is deficient , the ECF potassium ion concentration can rise above normal , when it rises 60 – 100 % above normal cardiac toxicity occur , causes weakness of heart contraction and development of arrhythmia .

14. 4. Excess aldosterone increases tubular hydrogen ion secretion , with resultant mild alkalosis .
Aldosterone causes secretion of hydrogen ions in exchange for sodium in the intercalated cells of the cortical collecting tubules , this decrease the hydrogen ion concentration in the ECF . This effect usually causes a mild degree of alkalosis .

16. Aldosterone stimulates sodium and potassium transport in sweat glands , salivary glands & intestinal epithelial cells
Aldosterone has almost the same effects on sweat glands and salivary glands as it has on the renal tubules . Both these glands form a primary secretion that contains large quantities of sodium chloride , but much of this is reabsorbed by excretory ducts ,whereas potassium and bicarbonate ions are secreted . The effect on the sweat glands is important to conserve body salt in hot environment and the effect on salivary glands is necessary to conserve salt when excessive quantities of saliva are lost . Aldosterone also greatly enhances sodium absorption by the intestines especially in the colon which prevents lose of sodium in the stools . The absence of aldosterone leads to diarrhea , with loss of salt from the body .

17. Regulation of aldosterone secretion
Four factors play essential roles in the regulation ;
Increased potassium ion concentration in the ECF greatly increases aldosterone secretion .
Increase activity of the rennin – angiotensin system greatly increases aldosterone secretion .
Increased sodium ion concentration in the ECF may slightly decrease aldosterone secretion .
ACTH from the anterior pituitary gland is necessary for aldosterone secretion , but has little effect in controlling the rate of secretion .

18. Of these factors , K + concentration & the rennin – angiotensin system are the most potent in regulating aldosterone secretion .
Activation of rennin – angiotensin system cause several fold increase in aldosterone secretion .
In turn , the aldosterone acts on the kidneys ;
To help the excrete the excess potassium ions .
To increase blood volume & arterial pressure thus returning rennin – angiotensin system toward normal , these feedback control mechanisms are essential for maintaining life .

19. Functions of the Glucocorticoids
95% of the glucocorticoid activity of the adrenocortical secretion results from the secretion of cortisol , known also as hydrocortisone , in addition small but significant amount of glucocorticoid activity is provided by corticosterone .

20. Effect of cortisol on carbohydrate metabolism
Stimulation of gluconeogenesis .
that is formation of carbohydrate from proteins & other substances by the liver this result mainly from two effects of cortisol :
a. Cortisol increases the enzymes required to convert amino acids into glucose in the liver cells .
b. cortisol causes mobilization of amino acids from the extra hepatic tissues mainly from muscle .
2. Decreased glucose utilization by the cells .
3. Elevated blood glucose concentration & adrenal diabetes .

21. Effect of cortisol on fat metabolism
Mobilization of fatty acids , this helps shift the metabolic system of the cells in times of starvation or other stresses from utilization of glucose for energy to utilization of fatty acids . Many people with excess cortisol secretion develop type of obesity , with excess deposition of fat in the chest & head regions of the body giving a buffalo like tor so and a rounded “ moon face “ this obesity result from excess food intake .

22. Cortisol is important in resisting stress & inflammation
Almost any type of stress causes an immediate & marked increase in ACTH secretion by the anterior pituitary followed by increased adrenocortical secretion of cortisol . Some different types of stress that increase cortisol release are the following ; Trauma , infection , intense heat or cold , injection of norepinephrine ,surgery , injection of necrotizing substances beneath the skin , any debilitating disease . Glucocorticoids cause rapid mobilization of amino acids & fats from their cellular stores making them immediately available both for energy & for synthesis of other compounds including glucose needed by different tissues of the body .

24. Anti-inflammatory effect of high levels of cortisol
When tissues are damaged by trauma ,by infection with bacteria , they almost become inflamed , the administration of cortisol can usually block this inflammation by ; 1. It can block the early stages of inflammation process . 2. If inflammation has already begun , it causes rapid resolution of the inflammation & increased rapidity of healing . Cortisol prevents shock or death in anaphylaxis .

25. Regulation of cortisol secretion by ACTH from the anterior pituitary
ACTH is a large polypeptide , has 39 amino acids .it is controlled by Corticotropin –releasing factor ( CRF) from the hypothalamus .

26. ACTH act on adrenocortical cells to produce steroids , Stress stimuli activate the entire control system to cause rapid release of cortisol & the cortisol in turn initiates a series of metabolic effects .there is direct feedback of the cortisol to both the hypothalamus & the anterior pituitary to decrease the concentration of cortisol in plasma . The secretory rate of CRF, ACTH & cortisol are high in early morning but low in the late evening .

28. Adrenal Androgens
The most important male sex hormone is dehydroepiandrosterone secreted by the adrenal cortex , also female sex hormones are secreted in small quantities as estrogen & progesterone some of the adrenal androgens are converted to testosterone in the extra-adrenal tissues.
Abnormalities of adrenocortical secretion
1. Hypoadrenalism __ Addison s disease is failure of adrenal cortex to produce adrenocortical hormones .
2. Hyperadrenalism __ cushing s syndrome .
3. Primary aldosteronism __ conn s syndrome , tumor of zona granulosa.

29. Disease of Adrenal glands
Addison’s disease
Decreased function of adrenal cortex
Excessive pigmentation, low blood pressure when standing, muscular weakness/fatigue, diarrhea, wt. loss, vomiting
Tx. Replace
hormone
Cushing’s syndrome
Hypersecretion of glucocorticoids
Causes hyperglycemia, hypertension, poor wound healing, bruising, “moon” face and obesity