Adrenal gland Flashcards
Name the zones of the adrenal cortex
Zona glomerulosa
Zona fasciculata
Zona rericularis
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- produced to stimulation through 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
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 from the anterior pituitary
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 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 If ECF falls renal perfusion pressure falls and macula dense cells sample K➡ renin➡ angiotensin 1➡ angiotensin 2 ➡ aldosterone increase renal Na retention to restore ECF
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
Increased H2O reabsorption- regulation of blood pressure- congental heart failure
Describe hyperaldosteronism
Primary- Conn’s syndrome
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
Dehydration, salt loss, weakness, make genitalia on females and precocious puberty in males
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 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
