S9: the adrenal glands + the renin, angiotensin, aldosterone system & adrenal disorders

Question 1

Describe the anatomical division of the adrenal gland in terms of the different layers of the cortex and the relationship between the cortex and medulla

Answer 1

Cortex: zona glomerulosa, zona fasiculata, zona reticularis
Zona glomerulosa = mineralocorticoids (aldosterone)
Zona fasiculata = glucocorticoids (cortisol)
Zona reticularis = glucocorticoids & small amounts of androgens
Medulla: chromaffin cells – adrenaline (80%) & noradrenaline (20%)

Question 2

Describe in general terms the structure and functions of the steroid hormones

Answer 2

Synthesised from cholesterol in adrenal glands & gonads
Lipid soluble hormones
Bind to receptors of the nuclear receptor family to modulate gene transcription

Question 3

Explain how corticosteroids exert their actions

Answer 3

Readily diffuse across plasma membrane
Bind to glucocorticoid receptors -> causes dissociation of chaperone proteins
Receptor ligand complex translocates to nucleus
Dimerisation with other receptors can occur
Receptors bind to glucocorticoid response elements or other transcription factors

Question 4

Explain the effects of androgens in males and females

Answer 4

Males: DHEA converted into testosterone in testes (after puberty this is insignificant as testes release far more themselves)
Females: promote libido & are converted to oestrogens by other tissues – after menopause this is only source of oestrogens
Promote axillary & pubic hair growth in both sexes

Question 5

Describe the action of aldosterone

Answer 5

Main actions in distal tubules & collecting ducts of nephron
Promotes expression of Na+/K+ promoting reabsorption of Na+ & excretion of K+
Therefore, influences water retention, blood volume & BP

Question 6

Explain how cortisol secretion is controlled by ACTH and CRH

Answer 6

Hypothalamus (reaction to stress) -> CRH -> stimulates anterior pituitary -> ACTH -> stimulates adrenal cortex -> cortisol -> stimulates target tissues
Cortisol has negative feedback actions on anterior pituitary & hypothalamus

Question 7

Explain how ACTH can lead to increased pigmentation in certain areas of the body

Answer 7

ACTH can activate melanocortin receptors on melanocytes
In Addison’s disease: decreased cortisol -> negative feedback on anterior pituitary reduced -> more POMC required to synthesise ACTH -> ACTH & MSH are produced from fragments of POMC

Question 8

Describe the main actions of cortisol

Answer 8

Increased protein breakdown in muscle
Increased lipolysis in fat
Increased gluconeogenesis in liver
Resistance to stress 
Anti-inflammatory effects 
Depression of immune response

Question 9

What are the glucocorticoid actions on metabolism?

Answer 9

Net effects: increased glucose production, breakdown of protein & redistribution of fat
Chronic high levels of cortisol can result in re-distribution of fat
-abdomen
-supraclavicular fat pads
-dorso-cervical fat pad (‘buffalo hump’)
-face (‘moon face’)

Question 10

What is Cushing’s syndrome? Describe the signs and symptoms

Answer 10

Chronic excessive exposure to cortisol – 4 causes
External causes (common) – prescribed glucocorticoids 
Endogenous causes (rare) – benign pituitary adenoma secreting ACTH (Cushing’s disease), excessive cortisol produced by adrenal tumour (adrenal Cushing’s) & non pituitary-adrenal tumours producing ACTH (small cell lung cancer)
Signs & symptoms = moon-shaped face, buffalo hump, abdominal obesity, purple striae, acute weight gain, hyperglycaemia & hypertension

Question 11

What are steroid drugs used for and what are their effects?

Answer 11

Used to treated inflammatory disorders eg. asthma, RA
Side-effects are same as the effects of higher levels of cortisol & can have mineralocorticoid effects
NOTE: steroid dosage should be reduced gradually & not stopped suddenly

Question 12

What is Addison’s disease?

Answer 12

Chronic adrenal insufficiency
Most common cause = destructive atrophy from autoimmune response
Signs & symptoms = postural hypotension, lethargy, weight loss, anorexia, increased skin pigmentation & hypoglycaemia

Question 13

What is an Addisonian crisis?

Answer 13

Life threatening emergency due to adrenal insufficiency
Precipitated by: severe stress, salt depravation, infection, trauma, cold exposure, over exertion & abrupt steroid drug withdrawal
Symptoms: nausea, vomiting, pyrexia, hypotension, vascular collapse
Treatment: fluid replacement & cortisol

Question 14

What are some examples of hormonal actions of adrenaline?

Answer 14

‘fight or flight’
Increased heart rate & contractility
Increased lipolysis in adipose
Increased bronchodilation in lungs
Increased renin secretion in kidney

Question 15

What is a phaeochromocytoma?

Answer 15

Chromaffin cell tumour
May precipitate life-threatening hypertension
Characteristics: headaches, palpitations, diaphoresis (excessive sweating), anxiety, weight loss & elevated blood glucose

Question 16

Describe the components and overall function of the renin angiotensin aldosterone system

Answer 16

Angiotensinogen cleaved by renin into angiotensin I
Angiotensin I -> angiotensin II which has 3 main effects to increase BP & blood volume
1) Vasoconstriction
2) Increases expression of Na+/K+ pump leads to increased reabsorption of Na+ and water back into blood
3) Translocation of aquaporin channels aids reabsorption of water back into the blood

Question 17

Describe hyperaldosteronism

Answer 17

Primary: defect in adrenal cortex, low renin levels
Most common is bilateral idiopathic adrenal hyperplasia
Secondary: over activity of RAAS, high renin levels
Signs: high BP, left ventricular hypertrophy, stroke, hypernatraemia, hypokalaemia
Treatment: adenomas removed by surgery, spironolactone (mineralocorticoid receptor antagonist)

Question 18

How do you distinguish between the different causes of Cushing syndrome?

Answer 18

ACTH test
Elevated ACTH – ACTH dependent cause -> do a high dose dexamethasone suppression test
-cortisol supressed = benign pituitary adenoma (Cushing’s disease)
-cortisol not supressed = ectopic tumour producing ACTH
Suppressed ACTH – ACTH independent cause -> have they taken prescribed glucocorticoids?
-yes = exogenous Cushing’s
-no = excess cortisol produced by adrenal tumour (Adrenal Cushing’s)