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The Adrenal Glands PartThe Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University [email protected] n

The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University [email protected]

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

The Adrenal Glands PartⅠThe Adrenal medulla

Ziying WANGInstitute of Pharmacology School of Medicine, Shandong [email protected]

Page 2: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Part 1 Introduction

Page 3: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Adrenal Glands

Page 4: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Blood supply

Page 5: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Nerve supply

AD

Page 6: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Embryology of the adrenal gland

Page 7: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Part 2 Adrenal medullaAt the interface between the neural

and endocrine system

Page 8: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

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 (↑ ↑ ↑ ↑)

Page 9: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Adrenal medulla

• Composed of polygonal cells arranged in cords or cluster

• Numerous wide diameter capillaries

• Sympathetic ganglion

Page 10: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Adrenal medulla chromate salt stain

– Brownish cytoplasm granules- when fixed by chromate salt containing fixative

– Also called chromaffin cell

Page 11: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Hormones of adrenal medulla

Catecholamines

Adrenaline

Noradrenaline

Dopamine

Peptides

Opiate peptides

Adrenomedullin

Arginine vasopressin

Vasoactive intestinal peptide

Page 12: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Catecholamine (CA)

Page 13: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Synthesis of catecholamine

Page 14: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Synthesis of catecholamine

• PNMT• Regulated by glucocorticoids.

Page 15: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Secretion of catecholamine

Page 16: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Regulation of catecholamine secretion

• The activity of the adrenal medulla is regulated by the activity of the sympathetic nerve.

Page 17: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

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

Page 18: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn
Page 19: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Actions of adrenal medullary hormones

• Fight and flight neuroendocrine response

• Emergency reaction hypothesis:

W. B. Cannon, 1928

• Through activating adrenoceptors

Page 20: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn
Page 21: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

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 (↑ ↑ ↑ ↑)

Page 22: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Part 3 Disorders of the adrenal medulla

Phaeochromocytoma: a tumor causes

adrenal medullary hormones over-secretion

Page 23: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

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

Page 24: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Case: treatment

(1) Drug treatment:α-blockers→β- blockers

(2) To find the source: CT and MIBG scan

(3) Operation

Page 25: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Familial Phaeochromocytoma

Page 26: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Part 3 Pharmacological uses of adrenal medullary hormones

Page 27: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Clinical uses of adrenaline

1. Cardiac arrest

2. Allergic shock: first choice

3. Bronchial asthma

4.Prolongation of local anesthetic duration

5. Topical hemorrhage

Page 28: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

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

x xx

x

Page 29: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Clinical uses of NA

1. Shock and hypotension

2. Upper digestive tract hemorrhage

Page 30: The Adrenal Glands Part Ⅰ The Adrenal medulla Ziying WANG Institute of Pharmacology School of Medicine, Shandong University wangziying@sdu.edu.cn

Endocrine hypertension

Belongs to secondary hypertension:

Conn’s syndrome

Cushing’s syndrome

Phaeochromocytoma