The Adrenal Glands Flashcards
What are the 2 regions of the adrenal gland and their composition?
- cortex: glandular tissue derived from mesoderm (3 regions: outer zona glomerulosa, middle zona fasciculata and inner zona reticularis)
- medulla: sympathetic nervous system derived from the neural crest
What hormones are secreted by the adrenal gland?
- zona glomerulosa: mineralcorticoids -aldosterone (maintain homeostasis of Na+, K+ and water)
- zona fasciculata:
glucocorticoids - cortisol and corticosterone (energy metabolism and glucose availability) - zona reticularis: gonadocorticoids - sex steroids (weak androgens)
- medulla: chromaffin cells secrete catecholamines
Describe the blood supply of the adrenal gland
- receives blood by the superior, middle and inferior adrenal arteries which dip into the cortex with some reaching the medulla and then anastomosing under the capsule
- contains adrenocorticoids which influence adrenaline production
Describe how steroid hormones are synthesised in the adrenal cortex and transported
- derived from cholesterol (from LDL in circulation)
- taken up by cells and converted to pregnenolone (rate limiting step and precursor of all hormones)
- can then be further converted until it forms its chosen hormone (depending on the factors it is exposed to)
- all hormones are lipid soluble and so can be carried around circulation attached to carrier proteins (eg. cortisol-binding globulins) which prolongs its half-life
Describe the short-term stress response
- governed by hypothalamus and pituitary gland
- adrenaline and noradrenaline by sympathetic NS
Describe the long-term stress response
- governed by hypothalamus stimulating the anterior pituitary gland to release ACTH
- results in release of cortisol (glucocorticoid) and aldosterone (mineralcorticoid) from the adrenal cortex
Describe the functions and effects of cortisol
- synthesised and released in response to physical and mental stress
- maintain glucose levels keeping constant (mobilisation)
- maintain BP (monitor blood volume) to resist stress-related changes
(95% of glucocorticoid activity) - sensitises medulla to catecholamines
Describe the activity levels of cortisol
- diurnal rhythm
- peaks in the morning at 6-8am
- is at its lowest around midnight-2am
- can be over-ridden by SNS in response to severe stress, and in disruption of the sleep-wake pattern
Describe the physiological actions of cortisol
- major role is stimulating gluconeogenesis in liver: mobilising amino acid from muscle protein and increasing enzyme involved in amino acid conversion of glucose (eg. glycogen to glucose)
- increases liver protein synthesis
- muscle cell: inhibits protein synthesis, increases proteolysis to release amino acids into circulation to be taken in by liver to generate more glucose
- adipose cell: decreased lipogenesis and increased lipolysis to release glycerol into circulation to be taken in by liver for gluconeogenesis
- antagonises effects of insulin
- stabilises lysosomes (dampens immune response)
Describe the role of the hypothalamus/pituitary in regulating cortisol release
- hypothalamus responds to stress which excites neurons within it
- stimulates release of CRF which induces anterior pituitary gland to synthesise and release ACTH which targets the adrenal cortex
- targets zona fasciculata to synthesise cortisol which is released to target tissue to carry out function
- stress is alleviated and cortisol levels feedback to the hypothalamus inhibiting further excitation and release
List the clinical features of Cushing’s Syndrome (excess glucocorticoids)
- hyperglycaemia (due to gluconeogenesis and steroid diabetes)
- muscle wasting (due to proteolysis)
- increase in FFA (redistribution of fat to face and trunk)
- tissue oedema, hyperkalaemia, hypertension (water and Na+ retention)
- GIT ulceration (excess H+ and decreased mucus)
- immunosuppression
- decrease in protein synthesis
What are the causes of Cushing’s Syndrome (excess glucocorticoids)
- ACTH-releasing pituitary tumour
- abnormal function of hypothalamus (high levels of CRH)
- ectopic ACTH-releasing tumour (eg. in lungs/pancreas/kidney)
- adrenal cortex tumour (hypersecretion of cortisol)
- clinical administration of glucocorticoid drugs
What is the treatment for Cushing’s Syndrome?
- surgical tumour removal
- decrease glucocorticoid drug use
Describe the main regulatory mechanism of aldosterone release
- high plasma K+ concentrations (detected by zona glomerulosa cells)
- can activate aldosterone release which acts on the kidney to decrease K+ (and also increase Na+ and water to maintain balance)
- therefore BP and blood volume also increases
- sends feedback to adrenal cortex
Describe the RAAS involvement in aldosterone regulation
- aldosterone causes kidney to release renin which activates angiotensinogen to form angiotensin I
- gets converted to angiotensin II by ACE
- angiotensin II targets the adrenal glands to release more aldosterone, and acts on brain to release CRH (leading to ACTH release) and ADH
Describe the cellular mechanism of action of aldosterone
- in kidney tubular cells binds to mineralcorticoid receptor to initiate gene expression
- results in increased expression of epithelial Na+ channels (ENaC) which reabsorbs urinary Na+
- increases activity of Na+/K+/ATPase
(Na+ reabsorbed with water, K+ secreted in urine - blood volume and BP increase)
What stops cortisol from binding to aldosterone mineralcorticoid receptors in the kidney tubules?
- 11beta-hydroxysteroid dehydrogenase which is an ezyme that binds to cortisol and converts it to cortisone
- cortisone has a lower affinity for receptor
What are the causes of Addison’s Disease (adrenal hormone deficiency)?
- autoimmune adrenalitis (adrenal failure - majority)
- TB/metastatic tumours
- impaired function of pituitary gland/decreased ACTH
- HIV (decreased immunity and increased viral/bacterial infections)
What are the clinical features of Addison’s Disease?
- weight loss/appetite loss
- muscle weakness
- nausea and vomiting
- low plasma glucose (lack of glucocorticoid actions)
- low plasma Na+ and high K+ (hyponatraemia and hyperkalaemia)
- lethargy and dizziness on standing due to hypotension
- skin pigmentation (excessive ACTH) - rare
What is the treatment of Addison’s Disease?
- glucocorticoid replacement therapy (hydrocortisone)
- IV saline infusion if severely dehydrated and give fludrocortisone (mineralocorticoid agonist)
Describe the synthesis of catecholamines
- synthesised from tyrosine (non-essential amino acid) into L-dopa
- induced by sympathetic stimulation and ACTH in chromaffin cells in adrenal medulla
- converted to dopamine by enzyme to end-product by further enzymes: adrenaline, noradrenaline (NT)
What are the effects of the catecholamines?
- increased HR, BP
- increased resp rate
- diversion of blood to muscles
- glucose mobilisation
What are the effects of NA binding to alpha-adrenergic receptors
- decreased cAMP
- increased Ca2+ conc
- contraction of smooth muscle
- relax intestinal smooth muscle
- decrease insulin secretion and PTH
- increased renin
What are the effects of A binding to beta-adrenergic receptors?
- increased cAMP
- decreased Ca2+ conc
- relaxation of smooth muscle
- contraction of cardiac muscle
- increased glycogenolysis and lipolysis
- increased erythropoiesis
- increased insulin, PTH and renin secretion
