The adrenal gland

Question 1

Where are the adrenal glands situated?

Answer 1

Above the right and left kidneys

Question 2

How is the blood supply of the adrenal gland organised?

Answer 2

Have many arterial connections but only 1 vein each
Left adrenal vein drains into renal vein
Right adrenal vein drains into IVC

Question 3

How is the adrenal gland structured?

Answer 3

Phrenic fascia encloses adrenal glands and kidneys

Adrenal gland consists of outer connective tissue capsule, cortex and medulla

Question 4

What is the cortex derived from?

Answer 4

embryonic mesoderm

Question 5

What is the medulla derived from?

Answer 5

ectodermal neural crest cells

Question 6

What is the role of the adrenal cortex?

Answer 6

Secretes cholesterol derived hormones: corticosteroids and androgens

Question 7

What 3 regions is the cortex divided into and what hormones does it secrete?

Answer 7

Zona glomerulosa: mineralocorticoids- aldosterone
Zona fasciculata: glucocorticoids - cortisol
Zona Reticularis: androgens and oestrogen

Question 8

What is the role of the adrenal medulla?

Answer 8

Contains chromaffin cells which secrete catecholamines into systemic circulation in response to stress

Question 9

What catecholamines are there?

Answer 9

Adrenaline (80%) and noradrenaline (20%)

Question 10

What hormones are derived from cholesterol?

Answer 10

Mineralocorticoids, glucocorticoids, androgens and oestrogen

Question 11

How is progesterone derived?

Answer 11

Cholesterol is converted to pregnenolone through a side chain cleavage
3- beta hydroxy steroid dehydrogenase oxidises hydroxyl group forming ketone group
This converts pregnenolone to progesterone

Question 12

How is aldosterone produced?

Answer 12

21- hydroxylase converts progesterone to 11-deoxycorticosterone
11- hydroxylase then converts this to corticosterone
18- hydroxylase converts corticosterone to aldosterone

Question 13

How is cortisol produced?

Answer 13

Progesterone is converted by 17- hydroxylase to 17- hydroxy-progesterone
21 hydroxylase converts this to 11-deoxycortisol
11 hydroxylase converts this to cortisol

Question 14

How is oestrogen produced?

Answer 14

Progesterone is converted by 17- hydroxylase to 17- hydroxy-progesterone
this is converted to sex steroid which are converted to androgens and then oestrogen

Question 15

What is the process of deriving hormones from cholesterol called?

Answer 15

Steroidgenesis

Question 16

How is cortisol transported through the body?

Answer 16

Cortisol is bound to corticosteroid binding globulin (75%), albumin (15%) and 10% is in the bioactive form and is unbound

Question 17

What system makes aldosterone?

Answer 17

Renin- angiotensin system

Question 18

What is the role of aldosterone?

Answer 18

Stimulates Na+ resorption in distal convoluted tubule (DCT) and cortical collecting duct (CCD)
Stimulates K+ and H+ secretion in DCT and CCD- lowers blood K+ levels
Increases water resorption (stimulates vasopressin) and increases blood volume and blood pressure

Question 19

Through what mechanisms does aldosterone work?

Answer 19

Aldosterone is cell membrane permeable and binds to intracellular receptors
Hormone receptor complex goes to nucleus where it acts as a transcription factor and binds to promotor regions on DNA- this leads to mRNA transcription and translation of ion pumps and enzymes
Aldosterone stimulates synthesis of Na+ channels in apical membrane

Question 20

What is renin released by?

Answer 20

Beta- adrenoreceptors on juxta-glomerular cells (cells which line ascending loop of Henle) release renin

Question 21

What 3 stimuli cause the release of renin?

Answer 21

1. Decreased arterial blood pressure (decreased renal perfusion pressure)
2. Increased renal sympathetic activity
3. Decreased Na+ load to top of loop of Henle

Question 22

What is the renin- angiotensin system?

Answer 22

Liver secretes angiotensin
Renin cleaves angiotensin to angiotensin I
Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II

Question 23

What is the role of angiotensin II?

Answer 23

Stimulates zona glomerulosa to produce aldosterone (stimulates enzymes needed: 3-beta- HSD, 21, 11 and 18- hydroxylase
REGULATES ALDOSTERONE RELEASE

Question 24

What are effects of cortisol?

Answer 24

Normal stress response
Stimulates peripheral protein catabolism (break down protein)
Hepatic gluconeogeneisis
Increases blood glucose conc.
Fat metabolism
Enhances effects of glucagon and catecholamines (Adrenaline and noradrenaline)
Weak mineralocorticoid effects (aldosterone)
Excretion of water load
Increased vascular permeability

Question 25

What controls cortisol release?

Answer 25

ACTH is released when stimulated by corticotrophin releasing hormone (anterior pituitary) This stimulates release of cortisol High cortisol levels lead to decrease in ACTH release which decreases CRH in hypothalamus (negative feedback) This is known as the hypothalamic-pituitary- adrenal axis

Question 26

How do cortisol levels change through the day?

Answer 26

Has a diurnal rhythm | This is a circadian rhythm

Question 27

What is Addison's disease?

Answer 27

Autoimmune disease where the immune system destroys the adrenal cortex TB bacteria in the adrenal glands (comment cause of primary adrenal failure) Pituitary starts secreting lots of ACTH and hence MSH (melanocyte stimulating hormone)

Question 28

What are symptoms of Addisons disease and what causes them?

Answer 28

1. Low blood pressure and hyponatremia (salt deficiency): reduced cortisol and aldosterone 2. Hyperkalaemia (increased K+): decreased aldosterone 3. Increased pigmentation and bronze pallor: Pro-opio-melanocortin is cleaved to form ACTH and MSH and endorphins. Increased POMC leads to increased ACTH which leads to increased MSH 4. Autoimmune vitiligo may coexist 5. Metabolic acidosis: H+ ion increase. Postural hypotension can lead to reduced blood flow to brain 6. Hypoglycaemia: reduced cortisol so reduced catecholamines 7. Infertility: reduction in sex steroids

Question 29

How can Addison's disease cause death?

Answer 29

``` Cortisol deficiency Aldosterone deficiency Salt loss Low blood pressure Death ```

Question 30

How do you treat Addison's disease?

Answer 30

Rehydrate with normal saline Give dextrose to prevent hypoglycaemia Give hydrocortisone or another glucocorticoid (cortisol or prednisolone- artificial steroid that is longer lasting and only has to be given once a day)

Question 31

What is Cushing's syndrome?

Answer 31

Concerned with elevated levels of cortisol primarily due to adrenal gland tumour (makes cortisol) or pituitary gland tumour (makes ACTH) Theres increased secretion of ACTH so increased secretion of cortisol Increased cortisol changes metabolism and causes weight gain- protein converted to fat

Question 32

What are symptoms of Cushing's syndrome?

Answer 32

Impaired glucose tolerence (diabetes) High BP Proximal myopathy (muscle weakness)- thins arms and legs and osteoporeisis Fat pads (buffalo humps)- fat between scapulae which is uncommon Mental changes Skin changes: (due to less protein) bruising, think skin, red cheek, red stretch marks, moon face Centripetal obesity

Question 33

What are 4 possible causes of Cushing's syndrome?

Answer 33

1. Taking steroids (glucocorticoids) orally 2. Pituitary dependent Cushing's disease (pituitary adenoma) 3. Ectopic ACTH (lung cancer) 4. Adrenal adenoma or carcinoma

Question 34

How are catecholamines made?

Answer 34

Tyrosine is converted to dopa which is converted to dopamine Dopamine is hydroxylated to form norepinephrine (noradrenalin) Methyl group is added to narepinephrin to make epinephrin (Adrenalin)

Question 35

What is the function of catecholamines?

Answer 35

Fight or flight- tachycardia, sweating, increased blood glucose, vasoconstriction

Question 36

How are catecholamines carried around the blood?

Answer 36

They're bound to albumin

Question 37

How are catecholamines degraded?

Answer 37

Degraded by 2 hepatic enzymes: | Monoamine oxidase and catechol-O-methyl transferase