S9 Adrenal Glands and RAAS Flashcards
What are the layers of the adrenal gland cortex (outside in)?
- zona glomerulosa
- zona fasciulata
- zona reticularis
What is produced in the zona glomerulosa?
Mineralocorticoids
E.g. aldosterone
What is produced in the zona fasiculata?
Glucocorticoids
E.g. cortisol
What is produced in the zona reticularis?
Glucocorticoids and a little of androgens
What is the cell type in the adrenal gland medulla?
What hormones do these cells produce?
Chromaffin cells
- adrenaline
- noradrenaline
What are the 3 types of corticosteroids?
- mineralocorticoids
- glucocorticoids
- androgens
What are androgens?
Sex hormones e.g. testosterone and oestrogens
What are the steroid hormones synthesised from? Are they lipid or water soluble?
Cholesterol
Lipid soluble
How do steroid hormones act on cells?
Bind to nuclear receptors and modulate gene expression
- Diffuse across plasma membrane
- Bind to glucocorticoid receptors
- Binding causes dissociation of chaperone proteins
- The receptor ligand complex translocates to the nucleus
- Dimerisation with other receptors occurs
- The receptors bind to glucocorticoid response elements (GREs) or other transcription factors on the DNA
How does the glucocorticoid-glucocorticoid receptor complex move within a cell?
Moves via translocation
What is the most abundant mineralocorticoid?
Aldosterone
What is the carrier protein for aldosterone?
Serum albumin
+ transcortin
What does aldosterone play a role in regulating?
Regulates plasma concentrations of Na+ and K+ by promoting the expression of the Na+/K+ pump - influences water retention, blood volume and blood pressure
What system is aldosterone a part of?
The renin-angiotensin-aldosterone system (RAAS)
What is hyperaldosteronism?
When too much aldosterone is produced
Hyperaldosteronism can be primary or secondary, what is each due to?
Primary - a defect in the adrenal cortex e.g. bilateral idiopathic adrenal hyperplasia or aldosterone secreting adrenal adenoma (low renin levels)
Secondary - due to over activity of the RAAS e.g. a renin producing tumour or a renal artery stenosis (high renin levels)
What are the 5 signs of hyperaldosteronism?
- hypertension
- left ventricular hypertrophy
- stroke
- hypernatraemia
- hypokalaemia
How do you treat hyperaldosteronism?
- if it’s an aldosterone producing adenoma - remove by surgery
- spironolactone - a mineralocorticoid receptor antagonist
What is the the most abundant corticosteroid?
Cortisol
Where is cortisol synthesised and release from? What is it’s synthesis and release in response to?
Zona fasciculata of the adrenal gland cortex
ACTH
How do cortisol inhibit it’s release?
By negative feedback, increased levels of cortisol tell hypothalamus to stop released CRH and hence ACTH
What type of hormone is cortisol?
How is cortisol carried in the blood?
Steroid hormone
By the carrier protein transcortin
How does the cortisol receptor exert it’s effects?
By regulating gene transcription
What are the 6 actions of cortisol?
- increase protein breakdown in muscle
- increase lipolysis in fat
- increase gluconeogenesis in liver
- resistance to stress - increase supply of glucose, raise BP (make vessels more sensitive to vasoconstrictors)
- anti-inflammatory - inhibit macrophages
- depression of the immune response - give to organ transplant patients
Describe the hypothalamic-pituitary-adrenal axis.
- Hypothalamus release CRH
- CRH acts on anterior pituitary resulting in release of ACTH
- ACTH acts on the adrenal cortex resulting in the release of cortisol (which has a negative feedback effect on the anterior pituitary or hypothalamus to inhibit it’s synthesis)
- Cortisol acts on target tissues
What are the net effects of glucocorticoid actions on metabolism?
- increased glucose production
- breakdown of protein
- redistribution of fat
What is Cushing’s syndrome?
A chronic excessive exposure to cortisol
What can cause Cushing’s syndrome?
External causes
* prescribes glucocorticoids (most common)
Endogenous causes (rare)
- Cushing’s disease - benign pituitary adenoma secreting ACTH
- Adrenal Cushing’s - excess cortisol produced by adrenal tumour
- Small cell lung cancer - non pituitary-adrenal tumours producing ACTH or CRH
What are the 7 signs and symptoms of Cushing’s syndrome?
- plethoric moon-shaped face
- buffalo hump
- abdominal obesity
- purple/red striae
- acute weight gain
- hyperglycaemia
- hypertension
What are steroid drugs used to treat?
Inflammatory disorders
- asthma
- irritable bowel disease
- rheumatoid arthritis
- autoimmune conditions
Suppress immune reaction in organ transplantation
What are the side effects on steroid drugs?
The same as high levels of cortisol
But don’t ever stop it as a treatment suddenly - do gradually
What is Addison’s disease? What’s the most common cause of it? Who is it more common in?
Chronic adrenal insufficiency
Destructive atrophy from autoimmune response (exact reason is unknown)
Women
What are the 6 signs and symptoms of Addison’s disease?
- postural hypotension
- lethargy
- weight loss
- anorexia
- increased skin pigmentation
- hypoglycaemia
Why does hyperpigmentation occur in Addison’s disease?
- Decreased cortisol
- This means negative feedback on the anterior pituitary gland is reduced
- So more POMC (pro-opiomelanocortin*) is required to synthesis ACTH
- POMC breakdown result in the production of ACTH —> MSH which leads to MELANIN SYNTHESIS, an immune response and decreased food intake
What is Addisonian crisis?
A life-threatening emergency due to adrenal insufficiency
What causes Addisonian crisis (7 things)?
- severe stress
- salt depravation
- infection
- trauma
- cold exposure
- over exertion
- abrupt steroid drug withdrawal
What are the symptoms of Addisonian crisis?
What is the treatment for it?
Nausea, vomiting, pyrexia, hypotension, vascular collapse
Fluid replacement, cortisol
Where are androgens secreted from?
Innermost layer of the adrenal cortex - zona reticularis
What are two types of androgens?
Dehydroepiandrosterone (DHEA)) and androstenedione
What regulates androgen secretion?
ACTH (and CRH)
What is DHEA converted to?
Testosterone in males in the testes
What do adrenal androgens do in women?
Promote libido and are converted into oestrogens by other tissues
Also only source of oestrogens after menopause
What do androgens promote in both sexes?
Axillary and pubic heart growth
Describe the adrenal medulla.
It’s a modified sympathetic ganglion of the ANS - chromaffin cells in the medulla don’t have axons but act as postganglionic nerve fibres that release adrenaline and noradrenaline into the blood
Why do some chromaffin cells only secrete noradrenaline (and not adrenaline)?
Don’t have the N-methyl transferase enzyme that converts noradrenaline into adrenaline
How is adrenaline made, what are all the intermediate products, etc?
Tyrosine —> levodopa —> dopamine —> NA —> adrenaline
QISS..
Alpha 1
Alpha 2
Beta 1
Beta 2
What receptors do adrenaline and NA act on?
Adrenergic receptors - GPCRs
What’s the response if adrenaline/NA binds to beta 1 or beta 2 receptors?
- Stimulators - alpha-s subunit on g-protein
- Adenylyl cyclase produces cAMP
- PKA acts on target proteins to cause a cellular response
What’s the response if adrenaline/NA binds to alpha 1 and alpha 2 receptors?
Alpha 1
- Alpha-i g-protein subunit - inhibitory
- Adenylyl cyclase is inhibiteds so no cAMP produced
- Means no PKA and no cellular response
Alpha 2
- Alpha-q g-protein subunit - stimulators
- Phospholipase C activated, produces DAG and IP3
- Activates PKC and Ca2+ release via IP3 receptors - cellular response
What effect does adrenaline have on the heart? Which receptor does it bind to?
Increases HR and contractility
Beta-1
What effect does adrenaline have on the lungs? Which receptor does it bind to?
Bronchodilation
Beta-2
What effect does adrenaline have on the blood vessels? Which receptor does it bind to for each?
Vasoconstriction - alpha 1
Vasodilation - beta 2
What is phaeochromocytoma?
A chromaffin cell tumour - rare tumour that secretes catecholamine (e.g. NA)
May cause life-threatening hypertension
What are the signs/symptoms of phaeochromocytoma?
- severe hypertension
- headaches
- palpitations
- diaphoresis (excessive sweating)
- anxiety
- weight loss
- high blood glucose
By what mode is catecholamine production and secretion induced - endocrine or neurocrine?
Neurocrine
What is the storage of corticosteroids and catecholamines?
Corticosteroids - synthesised and released
Catecholamines - stored in vesicles before release
If someone has a bilateral adrenalectomy, what do and don’t you need to give?
Need to give cortisol and aldosterone
Don’t need to give adrenaline - can live without
