18 Anatomy & Phsyiology of Adrenal Gland.pptx

sd

1. Anatomy & Physiology of Adrenal Gland Kidus Geremew, GSR I Moderator: Dr. Endale Anberbir Consultant General and Endocrine Surgeon October, 2021 1

2. Clinically relevant notes Outline Historical Background Introduction Embryology Anatomy Physiology References 2

3. Historical Background Bartolomeo Eustachi , 1563 Albert von Kölliker , (1817-1905) Thomas Addison, 1855 Edward Kendall, Tadeus Reichstein, and Philip Hench, 1950 Hans Selye, 1936 Roger Guillemin, Andrew Schally, and Rosalyn Yalow, 1977 3

4. Introduction ‘adrenal’ comes from ad- (Latin, ‘near’) and renes (Latin, ‘kidney’) Paired, mustard-colored structures Superior and slightly medial to the kidneys in the retroperitoneal space Among the most highly perfused organs in the body … 2L/kg/min ‘Two endocrine organs in one’ 4

5. Embryology 1 st week Zygote … implantation 2 nd week Bilaminar germ disc ‘ Week of 2s ’ 3 rd week Trilaminar germ disc ‘Gastrulation’ 4 th week Neurulation 5 ECTODERM Skin and appendages … epidermis, hair, nail, glands of skin Brain and spinal cord Neural crest cells Sensory ganglia [dorsal root of spinal cord] Schwann cells Pigment cells Odontoblasts Endocardial cushions Parafollicular cells Adrenal medulla NEURAL CREST CELLS Dorsal Pathway Melanocytes in the skin and hair follicles Ventral Pathway Sensory ganglia (dorsal ganglia) SNS and enteric neurons Schwann cells Cells of the adrenal medulla Parafollicular c-cells of thyroid

6. Cortex From mesoderm near gonads 4-5 wks. GA Definitive cortex Thin, outer part Future adult cortex Fetal cortex Thicker, inner part Functional … fetal adrenal steroids, 7-8 wks of GA Involutes after birth, 3 months 6 Ectopic cortical tissue is often located below the kidneys and associated with the testes or ovaries

7. Ectopic cortical tissue Ovaries, spermatic cord and testes Adrenocortical rests 50% of newborns Tend to atrophy and disappear after few weeks Enlarge in condition with continued corticotropin stimulation. Those within the scrotum may be misdiagnosed as testicular tumors 7

8. 8

9. Adrenocortical rests Rests vs adrenocortical tumors Known history of CAH Bilateral and confluent nodules Next to testicular hilum Round borders, attenuating echoes No calcifications N on- hypervascular on color Doppler 9

10. Medulla Ectodermal origin, neural crest cells Ectopic medullary tissues Neck, urinary bladder, para-aortic regions Organ of Zuckerkandl ‘ Paragangliomas ’ … more malignant potential 10

11. Fused adrenals Adrenal-renal fusion Adreno-hepatic fusion Adrenal agenesis Neuroblastoma Congenital adrenal hypoplasia Congenital adrenal hyperplasia 11

12. Anatomy Measures 5×3×1 cm Weighs 4-5g Shape Right: flattened, pyramidal Left: crescent shaped Proper capsule and Gerota fascia Extremely fragile 12 Gerota fascia is surgically important in dissection of the adrenal gland

13. Relationships Right adrenal Abuts posterolateral surface of retro-hepatic vena cava Right kidney infero -laterally Diaphragm superiorly Bare area of the liver antero-superiorly 13

14. Left adrenal lies between the left kidney and aorta Its inferior limb extending farther caudad toward the renal hilum than the right adrenal. Diaphragm posteriorly Tail of the pancreas and splenic hilum anteriorly 14

15. Arterial Supply Superior adrenal From the inferior phrenic artery Middle adrenal Small From the aorta Inferior adrenal From the renal artery Most prominent 15 Rich plexus beneath the glandular capsule … careful dissection, ligation and division during adrenalectomy

16. Variations Superior adrenal artery from Abdominal aorta Celiac trunk Intercostal artery … rarely Presenting as multiple arteries Middle adrenal artery from Inferior phrenic Renal, accessory renal artery SMA Celiac trunk Inferior adrenal artery from Abdominal aorta Inferior phrenic artery Accessory renal artery 16

17. Rare origin of a common trunk for the right inferior phrenic artery, and superior and inferior adrenal artery from the right renal artery . 17

18. Venous Drainage Right adrenal vein Short , 0.5cm Drains into IVC Left adrenal vein Longer, 2cm Joins the inferior phrenic vein and empties into left renal vein 18 Ligating right adrenal vein can be difficult Contributing factor in adrenal hemorrhage

19. Variations 5-10% Right Normal (> 80%); single vein directly into the IVC 20% - drain into right hepatic Territory of potential right adrenal vein confluence IVC–renal vein trifurcation Renal vein confluence 19 Vigilance about these variations reduces intra-op venous hemorrhage during adrenalectomy

20. Lymphatic Drainage Two plexuses Deep to capsule In the medulla Drain to Para-aortic nodes Lateral aortic nodes Thoracic duct 20

21. Nerve Supply Cortex The adrenal cortex receives only a vasomotor nerve supply. Sympathetic axons innervate the subcapsular arteriolar plexus. Medulla A neuroendocrine transducer - transforms the nervous signal into an endocrine signal Rich nerve supply Myelinated cholinergic preganglionic fibers from T5–T11 Pheochromocytes , equivalent to postganglionic sympathetic neurons. 21

22. Relative to its size, the adrenal has a larger autonomic supply than any other organ. Origin of cell bodies Intermediolateral cell column, T3-L3 The greater proportion of the innervation … ipsilateral greater thoracic splanchnic nerve (T5 - T9) 22 A pheochromocytoma, unlike the normal adrenal medulla, is not under neural control Spinal cord transection above T3 is associated with deficient epinephrine secretion

23. Cortex 2mm thick, > 80% of the gland Appear yellow … high lipid content Histologically, divided into 3 zones Zona glomerulosa Thin, outer part, 15% of cortex C onsists of small cells Moderately eosinophilic, lipid-poor cytoplasm Undulating inner border Mineralocorticoid production … Aldosterone 23

24. Zona fasciculata 75% of the adrenal cortex Long radial columns of large, clear, lipid-laden cells Appear foamy due to multiple lipid inclusions Production of glucocorticoids and DHEA Zona reticularis Small nests of compact, eosinophilic cells Production of adrenal androgens , estrogen , DHEA-S 24

25. Medulla 10-20% of the glands volume Reddish-brown in color Produces catecholamines hormones Epinephrine [ 80% ] Norepinephrine [20%] Dopamine [Minimal] Cells arranged in cords and are polyhedral in shape ‘ Chromaffin cells ’ 25

26. Physiology Production of Mineralocorticoids Glucocorticoids Sex hormones Catecholamines Cholesterol is the common precursor 26

27. Mineralocorticoids Consists Aldosterone 11-deoxycorticosterone (DOC ) Cortisol Aldosterone R.A.A.S and hyperkalemia … potent stimulators ACTH, pituitary pro-opiomelanocortin, and ADH … weak stimulators 27

28. Aldosterone is secreted at a rate of 50-250 μg /d Circulates in plasma chiefly as a complex with albumin Small amounts … bind to corticosteroid-binding globulin 30-50% … circulates in a free form Half-life of only 15-20 minutes and is rapidly cleared via the liver and kidney. A small quantity of free aldosterone also is excreted in the urine. 28

29. Mechanism of action of mineralocorticoids 29

30. Function Increase sodium reabsorption and potassium and hydrogen ion excretion at the level of the renal DCT Less commonly, aldosterone increases sodium absorption in salivary glands and GI mucosal surfaces 30

31. 31

32. Glucocorticoids Cortisol is the major adrenal glucocorticoid Only 10% is freely circulating and is the biologically active component 75% … bound to corticosteroid-binding globulin; 15% … bound to albumin Regulated by ACTH, CRH ACTH Stimulated by pain, stress, hypoxia, hypothermia, trauma, and hypoglycemia Secretion fluctuates, peaking in the morning and reaching nadir levels in the late afternoon … similar variation in the secretion of cortisol 32 Evaluating patients for glucocorticoid deficiency / excess

33. Physiology Cortisol is converted to di- and tetra- hydrocortisol and cortisone metabolites in the liver and the kidney. 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. 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. 33

34. Functions Glucose metabolism Gluconeogenesis , decreased muscle glucose uptake and metabolism Protein metabolism Decreased muscle protein synthesis, increased catabolism Fat metabolism Increased lipolysis 34

35. Immune system Reduces migration of inflammatory cells to sites of injury Increases circulation of PMNs, decreases lymphocytes, monocytes, eosinophils Cardiovascular Increases cardiac output and peripheral vascular tone Endocrine Inhibits TSH synthesis, decreases TBG levels, decreased conversion of T4 to T3 35

36. Connective tissue Inhibition of fibroblasts, loss of collagen, thinning of skin, stria formation Skeletal system Inhibition of bone formation, increased osteoclast activity, potentiate PTH 36

37. 37

38. Sex steroids Adrenal androgens are produced in the zona fasciculata and reticularis from 17-hyrdoxypregnenolone in response to ACTH They include Dehydroepiandrosterone ( DHEA ) and its sulfated counterpart ( DHEAS ) Androstenedione Small amounts of testosterone and estrogen 38

39. Physiology Adrenal androgens weakly bound to plasma albumin Exert their major effects by peripheral conversion to the more potent testosterone and dihydrotestosterone Androgen metabolites are conjugated as glucuronides or sulfates and excreted in the urine. 39

40. Functions Formation of male genitalia in fetus Secondary sexual characteristics at puberty Libido S ense of well being 40 Adrenal androgen excess … precocious puberty in boys; Virilization, acne, and hirsutism in girls and women

41. Catecholamines Epinephrine, Norepinephrine, and Dopamine Produced in the adrenal medulla Substrate - tyrosine Phenylethanolamine N-methyltransferase Converts NE to epinephrine Only present in the adrenal medulla and the organ of Zuckerkandl . 41 Differentiating adrenal medullary tumors from those situated at extra-adrenal sites

42. Catecholamines are stored in granules in combination with other neuropeptides, ATP, calcium, magnesium, and water-soluble proteins called chromogranins . Hormonal secretion is stimulated by various stress stimuli and mediated by the release of acetylcholine at the preganglionic nerve terminals. In the circulation, these proteins are bound to albumin and other proteins. Primarily metabolized in the liver and kidneys 42

43. Adrenergic receptors Transmembrane-spanning molecules that are coupled to G proteins α and β subtypes α-Adrenergic receptors … greater affinity for NE compared with E, and the opposite is true for β-adrenergic receptors 43

44. 44

45. Clearance Reuptake by sympathetic nerve endings Direct excretion by the kidneys Peripheral inactivation by catechol O-methyltransferase [ COMT ] and monoamine oxidase [ MAO ] Metanephrines , normetanephrins VMA 45 Pheochromocytoma work-up Treatment of depression … MAOI [Phenelzine, Selegiline …] Treatment of PKD … COMTI [ Comptan , Entacapon …]

46. References Schwartz's Principles of Surgery, 11 th Edition Sabiston Textbook of Surgery, The Biological Basis of Modern Surgical Practice, 20 th Edition, 2016 Textbook of Endocrine Surgery, 3 rd Edition Netter Atlas of Human Anatomy www.ncbi.nlm.gov Medscape 46

47. Thanks! 47