Adrenal Gland- Basic.

Adrenal gland, basic anatomy, embryology, physiology.

1. Dr. BIKASH CHANDRA SAH JR (2 ND YEAR )

2. Content…. Embryology Anatomy Physiology Pathology Treatment

3. Embryology .

4. Embryology It is composed of 2 endocrine glands. Outer cortex and inner medulla; each with distinct embryologic, anatomic, histologic, and secretory gland.

5. Adrenal cortex: Originate from mesodermal tissue near the gonads on the Adrenogenital ridge. Around the 5 th week Cortex divided into Thin definitive cortex: persist after birth to form adult cortex over first 03 years of life. Thicker and inner fetal cortex: Produce adrenal steroids by 8 th week of gestation. Involution (decrease in weight) after birth in 3 rd postpartum. Ectopic adrenocortical tissue may be found in the ovaries, spermatic cord, and testes

6. Adrenal medulla Ectodermal origin and A rises from neural crest 5th-6 th WOG. Neural crest cells migrate to the paraaortic and paravertebral areas and toward the medial aspect of the developing cortex to form the medulla . Most extra-adrenal neural tissue regresses but may persist at several sites. Adrenal medullary tissue also may be found in neck, urinary bladder and para -aortic regions Some factors for adrenal development: IGF2; GIP; dosage sensitve , sex reserve adrenal hypoplasia (DAX1) gene .

7. Anatomy Each kidney is caped by adrenal gland 2 Glands; Each 4 -5g . Right pyramidal . Left crescent shaped . Enclosed within Gerota’s( perirenal fascia) Composed of cortex and medulla. The adrenals are among the most highly perfused organs in the body, receiving 2000 mL/kg/min of blood , after only the kidney and thyroid.

8. Relations..

9. Rt. Adrenal gland Lt . Adrenal gland Anterior: Rt. lobe of liver and inferior Venacava Anterior: pancreas , lesser sac, and stomach Aorta lies near spleen lies superior and lateral to it. Posterior :Diaphragm Posterior : Diaphragm

10. Blood supply.

11. Artery supply: 03 arteries Superior adrenal arteries derived from inferior Phrenic artery Middle adrenal arteries derived from the aorta itself Inferior adrenal arteries derived from the renal artery . Note : arteries divide into about 50 arterioles to form rich plexus beneath glandular capsule require careful dissection and ligation during adrenalectomy . Lymphatics : The lymphatic vessels accompany the suprarenal vein and drain into the lumbar lymph nodes .

12. Venous drainage: Right adrenal vein: short and drains into IVC Left adrenal vein: longer and empties into Lt renal vein. Accessory vein: Rt side in 5-10% cases and drains into Rt. hepatic or rt. renal vein. Lt accessory vein drains directly into lt. renal vein.

13. Histology The adrenal cortex About 80% to 90% of the gland’s volume Appears yellow due to its high lipid content . D ivided into three zones—the Zona glomerulosa : outer area, consist of small cell and produce mineralocorticoid hormone and aldosterone Z ona fasciculate: made up larger cell, appear foamy due to multiple lipid inclusions. Produce glucocorticoid Z ona r eticularis cells are smaller. Secrete adrenal androgens

14. Adrenal medulla: Reddish-brown in color Constitutes up to 10% to 20 % of the gland’s volume The cells of the adrenal medulla are arranged in cords and are polyhedral in shape. R eferred to as chromaffin cells because they stain specifically with chromium salts .

15. Physiology

16. Adrenal cortex produce steroid hormones , C holesterol being precursor are generally derived from plasma or synthesized in adrenal cortex

17. Mineralocorticoids Major mineralcorticoids are 11- deoxycorticosterone (DOC), and cortisol Aldosterone secretion is regulated primarily by the renin-angiotensin system . Renin release from juxtaglomerular cells are stimulated by Decreased renal blood flow, Decreased plasma sodium, Increased sympathetic tone Angiotensin II, not only a potent vasoconstrictor, but also leads to increased aldosterone synthesis and release . Stimulator of aldosterone synthesis Hyperkalemia (potent,) whereas ACTH, pituitary pro-opiomelanocortin, and antidiuretic hormone are weak stimulators .

18. Kinetics Secreted at a rate of 50 to 250 μg /d (depending on sodium intake) Circulates in plasma Chiefly as a complex with albumin . Small amounts of the hormone bind to corticosteroid-binding globulin, and Circulates in a free form approximately 30% to 50% of secreted aldosterone. Half-life of only 15 to 20 minutes . Excretion : rapidly cleared via the liver and kidney. A small quantity of free aldosterone also is excreted in the urine also . Mechanism of action : Mineralocorticoids cross the cell membrane and bind to cytosolic receptors. The receptor-ligand complex subsequently is transported into the nucleus where it induces the transcription and translation of specific genes.

19. Function: Mainly to increase sodium reabsorption and potassium and hydrogen ion excretion at the level of the renal distal convoluted tubule . Less commonly, aldosterone increases sodium absorption in salivary glands and GI mucosal surfaces.

20. Glucocorticoids: Cortisol , major glucocorticoids Regulated by ACTH secreted by the anterior pituitary, which, in turn. 39-amino-acid protein, which is derived by cleavage from a larger precursor, pro-opiomelanocortin. Has trophic action for the adrenal glands. Secretion may be stimulated by pain, stress, hypoxia, hypothermia, trauma, and hypoglycemia. Secretion fluctuates, peaking in the morning and reaching nadir levels in the late afternoon. Shows a diurnal variation in the secretion of cortisol, P eak cortisol excretion also occurring in the early morning and D eclining during the day to its lowest levels in the evening.

21. Kinetics Circulation in plasma Bound primarily to corticosteroid-binding globulin (75%) and albumin (15%). Approximately 10% of circulating freely and is the biologically active component . Half-life : 60 to 90 minutes Determined by the extent of binding and rate of inactivation. Converted to di- and tetrahydrocortisol and cortisone metabolites in the liver and the kidney . Excretion: The majority (95%) of cortisol and cortisone metabolites are conjugated with glucuronic acid in the liver, thus facilitating their renal excretion . A small amount of unmetabolized cortisol is excreted unchanged in the urine

22. Mechanism of action: Glucocorticoid hormones enter the cell and bind cytosolic steroid receptors. The activated receptor-ligand complex is then transported to the nucleus where it stimulates the transcription of specific target genes via a “zinc finger” DNA binding element . Cortisol also binds the mineralocorticoid receptor with an affinity similar to aldosterone . However , the specificity of mineralocorticoid action is maintained by the production of 11β- hydroxysteroid dehydrogenase , an enzyme that inactivates cortisol to cortisone in the kidney

23. Sex Steroids : Adrenal androgens are produced in the zona fasciculata and reticularis from 17-hydroxypregnenolone in response to ACTH stimulation. They include Dehydroepiandrosterone (DHEA) and its sulfated counterpart (DHEAS), Androstenedione, and Small amounts of testosterone and estrogen.

24. Adrenal androgens are weakly bound to plasma albumin. They exert their effects Major effects by peripheral conversion to the more potent testosterone and dihydrotestosterone , Also have weak intrinsic androgen activity. Androgen metabolites are conjugated as glucuronides or sulfates. Excreted in the urine.

25. Function: During fetal development, adrenal androgens promote the formation of male genitalia. In normal adult males, the contribution of adrenal androgens is minimal; They are responsible for the development of secondary sexual characteristics at puberty . Adrenal androgen excess leads to Precocious puberty in boys and Virilization , acne, and hirsutism in girls and women.

26. Catecholamine

27. Catecholamine hormones: Epinephrine, norepinephrine, and dopamine Produced in In the central and sympathetic nervous system The adrenal medulla. The substrate, tyrosine, is converted to catecholamines via a series of steps Phenylethanolamine N- methyltransferase , which converts norepinephrine to epinephrine, is only present in the adrenal medulla and the organ of Zuckerkandl. Chromogranins : When catecholamines are stored in granules in combination with other neuropeptides, ATP, calcium, magnesium, and water-soluble proteins called Chromogranins.

28. Secretion stimulated by Various stress stimulus. And mediated by the release of acetylcholine at preganglionic nerve terminals. In circulation : are bound to albumin and other proteins. Excretion : Catecholamines are cleared by several mechanisms including Reuptake by sympathetic nerve endings, Peripheral inactivation by catechol O- methyltransferase and monoamine oxidase, and Direct excretion by the kidneys.   Metabolism: Takes place primarily in the liver and kidneys . Leads to the formation of metabolites such as metanephrines , normetanephrines , and VMA . which may undergo further glucuronidation or sulfation before being excreted in the urine

29. Metabolism: Takes place primarily in the liver and kidneys . Leads to the formation of metabolites such as metanephrines , normetanephrines , and VMA . which may undergo further glucuronidation or sulfation before being excreted in the urine

30. Mechanism of action: Adrenergic receptors are transmembrane -spanning molecules that are coupled to G proteins. Subdivided into α and β subtypes.   The receptor affinities for α receptors are—epinephrine > norepinephrine>> isoproterenol; β1 receptors —isoproterenol > epinephrine = norepinephrine; ands β2 receptors —isoproterenol > epinephrine >> norepinephrine.