Session 9 ILOs - The Adrenal glands, RAAS and Adrenal disorders Flashcards
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
Cortex - contains 3 layers, each producing different hormones (GFR, Salt, sugar, sex)
Zona Glomerulosa - produces mineralocorticoids e.g. aldosterone
Zona Fasciulata - produces glucocorticoid e.g. cortisol
Zona Reticularis - produces androgens
Medulla - contains chromaffin cells Produces Adrenaline (80%) and Noradrenaline (20%)
Different areas of the adrenal glands arise from different tissues, cortex is of mesoderm origin whereas the medulla is of neural crest cell origin
Name the hormones produced by the different layers of the adrenal cortex and explain their biological function(s)
Cortex
Zona Glomerulosa - mineralocorticoids e.g. aldosterone
- Main role in regulation of Na, K and arterial blood pressure
- Promotes expression of Na/K pump, promoting reabsorption of Na and extrusion of K which then affects blood pressure
Zona Fasciulata - glucocorticoid e.g. cortisol
- Has negative feedback to the hypothalamus to inhibit CRH and ATCH release
- Many actions but increases protein breakdown, increased lipolysis in fat, gluconeogensis in liver plus anti-inflammatory effect and immune response depression
Zona Reticularis - androgens
- Promote axillary and pubic hair growth in both sexes
- In males, DHEA converted to testosterone in testes
- In females, promote libido and converted to oestrogen by other tissues
Medulla
Adrenaline (80%) - fight or flight response
Noradrenaline (20%) - precursor of noradrenaline (N-methyltransferase required)
Describe in general terms the structure and functions of the steroid hormones
- All made from cholesterol in adrenal glands or gonads
- All lipid soluble
- Bind to nuclear receptors, therefore modulate gene transcription
Explain how the steroid hormones affect their target tissues
- Corticosteroids diffuse across plasma membrane
- Bind to glucocorticoid receptors which causes dissociation of chaperone proteins
- Receptor/ligand complex then relocates to the nucleus
- Dimerisation with other receptors
- Receptors bind to glucocorticoid response elements or other transcription factors
Explain how cortisol secretion is controlled by ACTH and CRH
- Cortisol is controlled by negative feedback of the hypothalamic pituitary adrenal axis
- Low ATCH or CRH would decrease cortisol production whereas increased ATCH or CRH would increase cortisol production
- However, high cortisol would inhibit ATCH or CRH production therefore lowering cortisol levels again
Explain how ACTH can lead to increased pigmentation in certain areas of the body
- ACTH is made from POMC, so if there is more ATCH then there needs to have been more POMC to make it
- However POMC also makes MSH (melanin stimulating hormone) which increases melanin production and therefore hyperpigmentation
Describe the main actions of cortisol
- Negative feedback to the hypothalamus to inhibit CRH and ATCH release
- Increases protein breakdown
- Increased lipolysis in fat
- Gluconeogensis in liver
- Anti-inflammatory effect
- Immune response depression
Describe in general terms the structure and functions of adrenaline
Adrenaline is formed from Tyrosine
Tyrosine -> Levodopa -> Dopamine -> Noradrenaline -> Adrenaline
N-methyltransferase is required to convert Noradrenaline to Adrenaline
Adrenaline binds to adrenergic receptors involved in the sympathetic or fight or flight response
Explain how adrenaline exerts its effects on cells
Adrenaline binds to adrenergic receptors involved in the sympathetic or fight or flight response
QISS (a1, a2, b1, b2)
Describe the components and overall function of the renin angiotensin aldosterone system
The RAAS system is a system of hormones involved in the regulation of Na concentration and arterial blood pressure
- The system is triggered if the concentration of plasma Na+ or the blood flow through the kidney falls, the juxtaglomerular cells of the kidney nephrons release renin
- Renin converts angiotensinogen to angiotensin I
- ACE converts angiotensin I into angiotensin II
- Angiotensin II acts on AngII receptors to have 3 main effects
1. Vasoconstriction of arterioles
2. Increased expression of Na/K pump at kidney
3. Aldosterone production from adrenal glands (also acts on kidneys)
Explain the effects of over-secretion and under-secretion of cortisol
Over-secretion of cortisol = Addison’s disease
- Weakness, tiredness, weight loss, hypoglycaemia
Under-secretion of cortisol = Cushing’s syndrome
- Weight gain
- Cushingoid features (classic cushing’s appearances)
Describe tests of adrenal cortical function
- Measurement of plasma cortisol and ACTH levels and the 24hr urinary excretion of cortisol and its breakdown products
- Dexamethasone suppression tests and ACTH stimulation tests) may be used in the differential diagnosis of adrenocortical disease
- Dexamethasone (potent synthetic steroid) that normally suppresses secretion of ACTH and thus cortisol
- Low dose Dexamethasone initially to see whether there is any suppression of cortisol at all (to generally confirm Cushing’s syndrome)
- High dose Dexamethasone if there is no suppression on low dose
- Levels of ATCH and cortisol can reveal whether there is Cushing’s disease (excess ATCH production from pituitary), adrenal Cushing’s (adrenal production of excess cortisol) or an ectopic source of cortisol production (e.g. lung cancers)
Explain how cortisol can have weak mineralocorticoid and androgen effects
At high concentrations, cortisol can have weak mineralocorticoid and androgen effects
- The actions of cortisol on target tissues are mediated by binding to receptors in the cytoplasm/nucleus
- All steroid hormone receptors have similar basic structure with hormone and DNA binding domains
- The hormone binding domains of the mineralocorticoid and androgen receptors have over 60% sequence homology with the hormone-binding domain of the glucocorticoid receptor
- Thus, cortisol can bind to these receptors to a limited extent causing their partial activation
