11,12 Adrenal function Flashcards
What does endocrine system excrete ?
hormones
regulate growth, development, metabolism, reproduction
The adrenal glands secretes a variety of steroid and amine hormones.
The anatomy and function of Adrenal glands ?
located at the superior pole of each kidney (suprarenal): they consist of an inner medulla and an outer cortex.
* 2 distinct endocrine functions; secretion
o Catecholamines (adrenaline, A & noradrenaline, NA) in response
to sympathetic nerve activation.
o 3 classes of steroid hormones:
glucocorticoids (e.g. cortisol),
mineralocorticoids (e.g.
aldosterone) and sex steroids.
Functions as a autonomic ganglion of sympathetic division :fight /flight
What is Catecholamines biosynthesis ?
Catecholamines are amine hormones
(modified amino acids):
o Tyrosine derivatives; water-soluble.
o Packaged into vesicles, released by
exocytosis when needed (in blood).
What is GPCR ?
beta adrnergic receptor
1. β2 adrenoceptors activated by NA / A.
2. Activation of adenylate cyclase (AC)
enzyme, via Gs subunit…
3. …Liver: glycogenolysis and also
gluconeogenesis (even vasodilation).
What are some short-term stress response ?
o Increase heart rate & force of contraction.
o Increase systolic and diastolic blood pressure (BP).
o Increase respiration rate.
o Increase levels of sugar/glucose and fats/lipids in the blood.
* EpiPen (brand): contains a dose of adrenaline; can be life-saving if a
person is suffering from a severe allergic reaction (anaphylaxis).
What is the clinical disorder of adrenal medulla ?
Phaeochrocytoma
Catecholamines = dispensable.
* Under-production is not a clinical problem; however, excessive
secretion of catecholamines can have serious consequences.
* Over-production (/overactivity) can be caused by a tumour of chromaffin cells
o Are rare; can occur sporadically, or as part of familial syndromes.
Excessive, unregulated catecholamine
release (at “inappropriate times”) results in distinctive symptoms: sweating, headaches, palpitations, hypertension.
* Treatment: drugs, e.g. α-, or non-selective β blockers surgery.
Where are steroid hormones derived from ?
usually take several hours-days
cortisol
o Cholesterol derivatives; lipid-soluble (hydrophobic).
o Transported in the blood bound to carrier proteins.
o Readily cross plasma membrane. Diffuse out of cells that produce them → synthesised ‘on demand’ (when needed).
o Bind receptors found inside the cell: intracellular receptors →regulate gene expression.
Cholesterol must enter mitochondria for
steroidogenesis; enzyme CYP11A1 / P450SCC localised to inner mitochondrial membrane.
* StAR promotes the transfer of cholesterol across the aqueous space separating the outer and inner mitochondrial membranes
What is StAR ?
rate-limiting step in steroidogenesis
1. Adrenocorticotropic hormone (ACTH)
binds to the melanocortin receptor 2:
MC2R (G protein-coupled receptor).
2. Gα subunit activates adenylate cyclase.
3. AC converts ATP into cyclic 3 ,5 -
adenosine monophosphate (cAMP).
4. cAMP activates protein kinase A (PKA).
5. PKA phosphorylates cAMP response
element binding (CREB) transcription
factor
6. CREB activates gene transcription →
cortisol production.
7. PKA will also activate e.g. StAR, so to
initiate steroidogenesis
Cortisol in Adrenal cortex ?
Control of (mostly) carbohydrate and
protein metabolism.
* Antagonist to insulin: ↑ plasma [glucose].
* Counteracts stress: trauma, intense heat or cold, infection…
* Maintains glucocorticoid in humans
What is therapeutic use of glucocorticoids ?
Potent, synthetic glucocorticoids (corticosteroids, e.g. prednisolone)
used in range of autoimmune and inflammatory disorders for their immunosuppressive and anti-inflammatory properties.
* Caution: should be used short-term
* Concerns over long-term safety:
increases risk of infections, diabetes
(hyperglycaemia), osteoporosis
(due to increased bone resorption),
gastrointestinal and cardiovascular
Wahat are some eg of clincal disorders of adrenal cortex ?
Cushing’s syndrome, Conn’s syndrome and Addison’s disease
What is tertiary,secondary,primary pathway ?
3-Disease is in hypothalmus
2-disease is in anterior pituitary; end organ is affected downstream.
1-disease is in end organ, e.g. adrenal gland.
o Most common.
What is cushings syndrome ?
Patients with Cushing’s syndrome have a characteristic appearance:
o Fat deposition in face (“moon face”) and trunk; loss elsewhere.
o Muscle tissues wasting (protein mobilisation).
o Skin is thin, easily bruised; poor wound healing.
Treatment:discontinue drugs,
or give drugs, e.g. metyrapone (cortisol-lowering); surgery (if tumour).
What is Conns sydrome ?
Overproduction of aldosterone may
arise
o Hyperactivity of zona glomerulosa
cells: 1° hyperaldosteronism.
o Excessive secretion of the enzyme
renin: 2° hyperaldosteronism.
* Main function of mineralocorticoids is to regulate electrolyte/salt concentrations in ECF, especially Na+ and K+
Aldosterone excess may result in Na+
retention; loss of K+ (hypokalaemia);
alkalosis → hypertension (↑ BV).
* Treatment: drugs, e.g. spironolactone
(aldosterone antagonist).
What is Addisons syndrome ?
Addison’s syndrome (/disease) usually involves deficits in the levels
of both glucocorticoids and mineralocorticoids:
o Rare; symptoms: progressive weakness; individuals lose weight.
o Na+ levels ↓ (hyponatraemia); K+ levels ↑ (hyperkalaemia);
plasma glucose levels also ↓.
* Common: severe dehydration and hypotension
* Causes: damage to adrenal glands or pituitary;most common: autoimmune disease (→ destruction of adrenal tissue; i.e. primary (1°) hypoadrenalism).
* Treatment: usually drugs, e.g. hydrocortisone (cortisol)
and/or fludrocortisone (synthetic mineralocorticoid), i.e.
oral replacement therapy
