1. The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

2. Part 1 Introduction

3. Adrenal Glands

4. Blood supply

5. Nerve supply AD

6. Embryology of the adrenal gland

7. Part 2 Adrenal medulla At the interface between the neural and endocrine system

8. Case: Mrs. Smith, a 45-year-old woman Worried for panic attacks –Sweating –Palpitation –Sudden episodes of rapid heart beating –Frightened Examination –Pale –P: 100/min –BP: 155/105 to 260-165 mmHg Investigation –Serum sodium: 141mmol/L (→) –Serum potassium : 3.2mmol/L (↓) –Plasma noradrenaline: 12nmol/L (↑ ↑) –Plasma adrenaline: 6.7nmol/L (↑ ↑ ↑ ↑)

9. Adrenal medulla Composed of polygonal cells arranged in cords or cluster Numerous wide diameter capillaries Sympathetic ganglion

10. Adrenal medulla chromate salt stain –Brownish cytoplasm granules- when fixed by chromate salt containing fixative –Also called chromaffin cell

11. Hormones of adrenal medulla Catecholamines Adrenaline Noradrenaline Dopamine Peptides Opiate peptides Adrenomedullin Arginine vasopressin Vasoactive intestinal peptide

12. Catecholamine (CA)

13. Synthesis of catecholamine

14. PNMT Regulated by glucocorticoids.

15. Secretion of catecholamine

16. Regulation of catecholamine secretion The activity of the adrenal medulla is regulated by the activity of the sympathetic nerve.

17. Transport and metabolism of adrenal medullary hormones (1) No specific binding proteins (2) Onset rapid and short-lived (3) Metabolized by COMT and MAO (4) End product: VMA

19. Actions of adrenal medullary hormones Fight and flight neuroendocrine response Emergency reaction hypothesis: W. B. Cannon, 1928 Through activating adrenoceptors

21. Case: What is the cause? Over-secretion of the CA –Palpitation –Sudden episodes of rapid heart beating –Frightened –Pale –P: 100/min –BP: 155/105 to 260-165 mmHg –Plasma noradrenaline: 12nmol/L (↑ ↑) –Plasma adrenaline: 6.7nmol/L (↑ ↑ ↑ ↑)

22. Part 3 Disorders of the adrenal medulla Phaeochromocytoma: a tumor causes adrenal medullary hormones over-secretion

23. Phaeochromocytoma Symptoms: with emergency reaction frequently Diagnosis (1) CT and MIBG: localization (2) Symptoms: HBP, HG, high BMR (3) VMA, AD and NA in urine Treatment (1) Operation (2) Adrenoceptor antagonists α-adrenoreceptor blockers β-adrenoreceptor blockers

24. Case: treatment (1) Drug treatment:α-blockers→β- blockers (2) To find the source: CT and MIBG scan (3) Operation

25. Familial Phaeochromocytoma

26. Part 3 Pharmacological uses of adrenal medullary hormones

27. Clinical uses of adrenaline 1. Cardiac arrest 2. Allergic shock: first choice 3. Bronchial asthma 4.Prolongation of local anesthetic duration 5. Topical hemorrhage

28. bronchial mucosa vessel dilation ↑HA, SRS, PGs, BK Ag-Ab Allergized cells Bronchial SM contraction dyspnea Intrathoracic pressure↑ ↓returned blood volume ↓SBP Vessel dilation DBP↓ mucosal edema AD: first choice for allergic shock AD x xx x x

29. Clinical uses of NA 1.Shock and hypotension 2. Upper digestive tract hemorrhage

30. Endocrine hypertension Belongs to secondary hypertension: Conn’s syndrome Cushing’s syndrome Phaeochromocytoma