Adrenal gland 4th and 5th lectures Flashcards
Name the zones of the adrenal cortex
Zona glomerulosa (produce mineralalocorticoids)
Zona fasciculata (produce glucocorticoids)
Zona rericularis (produces androgens)
All 3 in cortex
Catecholamine synthesis in medulla
Name some adrenal cortex hormones
Corticosteroid- glucocorticoids, mineralcorticoids, Androgens
Derived from cholesterol, synthesised using p450 cytochrome enzymes
Describe steroid synthesis
Cholesterol is transported to the inner mitochondrial membrane by StAR (rate limiting step) - produced to stimulation through a cAMP Promoted by ACTH, LH Suppressing by alcohol
P450scc cleaves cholesterol to pregnenolone- activity increased by ACTH, two hydroxylase reactions and cleavage between 20-22- works in a complex with reductase enzymes
Describe glucocorticoids
21 carbons
Types; Cortisol- active Corticosterone Cortisone- inactive
CYP11B1 convert cortisol
Cortisol is transported via transcortin (80%) and albumin (10%)
Triggered by emotion, biochemical, and diurnal rhythm➡ CRH releases corticotropin (ACTH) from the anterior pituitary (regulated by ADH), which binds to the adrenal cortex releasing cortisol which is a negative feedback system.
Immediate effects- increase StAR activity Subsequent- gene transcription of hydroxylases, LDL receptors
Long-term- increase size and functional complexity of organelles, size and number oif cells➡ hyperplasia
What are the actions of glucocorticoids?
Intracellular receptors dimerises➡ glucocorticoid response element➡ protein synthesis eg. Lipocortin Increases plasma glucose, increase gluconeogenesis
Increase protein breakdown in muscles, Increase protein synthesis in liver, Fat redistribution to trunk, Decreased bone calcium absorption = osteoporosis, Mood changes, Decreased lymphocytes, Decreased allergies
Describe an excess of glucocorticoids
Cushings syndrome- pituitary tumour (Cushing’s disease), ectopic ACTH producing tumour, autonomous adrenal adenoma, iatrogenic- long term immunosuppression with synthetic cortisol analogues Symptoms- obesity, moon face, hypertension, osteoporosis, hypokalaemia, purple striae Treat with CYP11B1 (11 hydroxylase) inhibitor (metyrapone)
Describe a decrease of adrenal function
Primary- Addison’s disease- mostly autoimmune Symptoms- fatigue and hypoglycemia, weight loss, skin pigmentation and ion imbalance, treat with cortisol replacement therapy
Secondary- disease of pituitary results in decrease ACTH release and wasting of the adrenal gland
Describe mineralocorticoids
Increase extracellular volume and therefore blood pressure 21 carbons Eg. Aldosterone
Synthesised in zona glomerulosa from progesterone (21 hydroxylase)➡ 11-deoxycorticostrerone (11 hydroxylase)➡ corticosterone➡ 18-hydroxycorticostrerone (aldosterone synthesis)➡ aldosterone
Transported in blood- 50% bound to protein, albumin and transcortin and 50% free
Describe aldosterone sectretion
ACTH- increase will increase Plasma K- increae will increase Plasma Na- decrease will increase Renin-angiotensin- aldosterone system.
Role of aldosterone is to decrease K+ levels and increase Na+ levels using renin-angiotensin system
If ECF falls renal perfusion pressure falls and macula dense cells sample K➡ renin production ➡ angiotensin 1➡ angiotensin 2 ➡ aldosterone increase renal Na retention and water to restore ECF (extracellular fluid)
Describe aldosterone action on target cells
Binds to mineralocorticoid receptor (MR) Has equal affinity to cortisol and there is much more cortisol in the blood than aldosterone
11b-HSD2 mops up excess cortisol in cells in the kidney by metabolising it to the inactive cortisone Once bound aldosterone upregulated proteins for Na handling
Describe the systemic effects of mineralocorticoids
Increased sodium reabsorption in DCT and CD of kidney, sweat glands, salivary glands, GIT
Decreased K reabsorption
Increase H loss- metabolic alkalosis and Increased H2O reabsorption- regulation of blood pressure- congental heart failure
Describe hyperaldosteronism
Primary- Conn’s syndrome
Caused by Hyperplasia or adrenal adrenoma in zona glomerulosa
Renin levels normal or low
Symptoms- hypertension, alkalosis, hypokalaemia
Treatment- surgery, spironolactone
Secondary- Renal artery stenosis, diuretic therapy, excess liquorice ingestion- 11b-HSD inhibition Renin levels are high
Describe adrenal androgens
Synthesised on small amounts in the zona reticularis
DHEA and androstenedione- may cause growth of pubic and auxiliary hair and female libido
What is CAH?
Congenital androgen hyperplasia
Symtoms : Dehydration, salt loss, weakness, make genitalia on females and precocious puberty in males, large adrenal gland
Treated with corticosteroid replacement Eg. Autosomal recessive 21 hydroxylase mutations Decrease glucocorticoid and mineralocorticoid production that decreases negative feedback and therefore increases ACTH leading to increased DHEA and excess angrogens to be prodcued causing adrenal hyperplasia
Describe the adrenal medulla
Part of autonomic nervous system
Specialised ganglia supplied by sympathetic preganglionic neurones (ACh as transmitter)
Synthesises catecholamines- adrenaline
Not essential for life
The medulla interacrs with nervous system to produce catacholamines. Cromaffin cells are within the medulla and are an extention of the nervous system.
