The adrenal glands Flashcards
Describe the location of the adrenal glands.
Lie retroperitoneally on the upper pole of the kidneys
How does the adrenal cortex arise?
arises from intermediate mesoderm
How does the adrenal medulla arise?
- Develops from neural crest cells
- CHROMAFFIN cells produce catecholamines
- Controlled directly by preganglionic sympathetic neurones
(thus chromaffin cells are equivalent to postganglionic sympathetic neurones)
Describe the anatomy of the adrenal gland.
EXTERNAL TO INTERNAL: Capsular artery Capsule Zona glomerulosa Zona fasciculata Zona reticularis Medulla Medullary vein
What hormones are released from the medulla?
Epinephrine
What hormones are synthesized and released from the zona reticularis?
Androgens (DHEA and androstenedione)
and cortisol
What hormones are synthesized and released from the zona fasciculata?
Glucocorticoids (e.g.. cortisol)
What hormones are synthesized and released from the zona glomerulosa?
Mineralocorticoid (aldosterone)
What is secreted and controls secretion from the zona glomerulosa?
What is it involved in?
- Mineralocorticoids – e.g. aldosterone
- Controlled by renin – angiotensin
- Involved in: Electrolyte and fluid homeostasis
What is secreted and controls secretion from the zona fasciculata.
What is it involved in?
- Glucocorticoids – e.g. cortisol
- Secretion controlled by ACTH
- Involved in: Carbohydrate, lipid and protein Metabolism
What is secreted and controls secretion from the zona reticularis.
What is it involved in?
Sex steroids – androgens
Describe the blood supply of the adrenal cortex.
Supplied by the superior middle and inferior adrenal arteries; anastomose under the capsule
Describe the effects of the short term stress response.
- Increased heart rate
- Increased blood pressure
- Liver converts glycogen to glucose and releases glucose to blood
- Dilation of bronchioles
- Changes in blood flow patterns leading to decreased digestive system activity and reduced urine output
- Increased metabolic rate
Describe the effects of the long term stress response.
MINERALOCORTICOIDS:
- Retention of sodium and water by kidneys
- Increased blood volume and blood pressure
GLUCOCORTICOIDS:
- Proteins and fats converted to glucose or broken down for energy
- Increased blood glucose
- Suppression of the immune system
What is the role of cortisol?
Major role in ability to cope with physical (trauma, infection, allergies) or neurological (anxiety, restraint) stresses
Describe the pharmacology of cortisol.
anti-inflammatory / anti-allergic / anti-immune actions
What is Cushing’s disease?
glucocorticoid excess
What are the causes of Cushing’s disease?
- ACTH-releasing pituitary tumour
- Ectopic ACTH-releasing tumour (usually in lungs, pancreas or kidney)
- Tumour of the adrenal cortex - hyper-secretion of cortisol
- Administration of pharmacological doses of glucocorticoid drugs
What are the clinical features of Cushing’s disease?
- Hyperglycaemia due to gluconeogenesis in liver- adrenal/steroid diabetes
- Muscle wasting - loss of protein synthesis in muscle and bone (and most tissues)
- Increase in FFA in plasma (reduced lipogenesis and enhanced lipolysis)
- Increased insulin release - redistribution of fat stores to face, neck, upper trunk
“buffalo hump”; β-cell exhaustion - Tissue edema, hypokalemia, hypertension - due to increased glomerular filtration
(glucocorticoid effect) and water and Na+ retention (mineralocorticoid effects) - GI Tract ulceration - due to excess H+ secretion and decreased mucous production
(alkalosis due to increased H+ loss in GI tract and kidney) - Decreases in protein synthesis - increased neural excitability, lymph node lysis,
inhibition of haematopoiesis and lymphocyte production, - immunosuppressive and anti-allergic and anti-inflammatory actions)
What are the treatments for Cushing’s disease?
Surgical removal of tumour / decreases in drug dosage
What is Addison’s disease?
primary adrenal cortical insufficiency
What are the primary causes of Addison’s disease?
- Tuberculosis/ metastatic tumours
- Autoimmune adrenalitis - adrenal failure
- HIV - decreased immunity and increased viral and bacterial infections
- Atrophy due to prolonged steroid therapy
What are the clinical features of Addison’s disease?
- Loss of weight/appetite, muscle weakness, nausea, vomiting.
- Low plasma glucose esp. after fasting (lack of glucocorticoid actions)
- Low plasma Na+ (hyponatriemia) and high plasma K+ (hyperkalaemia) (due to lack of
mineralocorticoids) . - Dehydration and hypotension due to 3. - systolic blood pressures 50-80 mmHg.
- Lethargy and dizziness on standing up due to 4.
- Severe cases present with skin pigmentation due to excess ACTH acting as MSH
What is Addison’s disease?
primary adrenal cortical insufficiency
What do the two populations of chromatin cells secrete?
Either:
Epinephrine (adrenaline) (majority of cells) OR
Norepinephrine (noradrenaline)
Also been shown to secrete:
Dopamine
Enkephalins (pain control)
What are the adrenocortical hormones?
- Mineralocorticoids (chiefly aldosterone)
- Glucocorticoids (chiefly cortisol)
- Gonadocorticoids (chiefly androgens, converted to testosterone or estrogens after release)
What are the adrenal medullary hormones?
- Catecholamines (epinephrine and norepinephrine)
Describe the regulation of release of Mineralocorticoids.
Stimulated by renin-angiotensin mechanism (activated by decreasing blood volume or blood pressure), elevated K+ or low Na+ blood levels, and ACTH (minor influence)
Inhibited by increased blood volume and pressure, increased Na+ and decrease K+ blood levels
Describe the target organs and effects of Mineralocorticoids.
Kidneys: increase blood levels of Na+ and decrease blood levels of K+; since water reabsorption accompanies sodium retention, blood volume and blood pressure rise.
Describe the effects of hyper-secretion and hypo-secretion of Mineralocorticoids.
HYPERSECRETION:
Aldosteronism
HYPOSECRETION:
Addison’s disease
Describe the regulation of release of Glucocorticoids.
Stimulated by ACTH
Inhibited by feedback inhibition exerted by cortisol
What are the adrenal medullary hormones?
- Catecholamines (epinephrine and norepinephrine)
Describe the effects of hyper-secretion and hypo-secretion of Glucocorticoids.
HYPERSECRETION:
Cushing’s syndrome
HYPOSECRETION:
Addison’s disease
Describe the regulation of release of Gonadocorticoids.
Stimulated by ACTH
Mechanism of inhibition incompletely understood, but feedback inhibition not seen
Describe the target organs and effects of Gonadocorticoids.
Insignificant effects in males
Responsible for female libido; development of pubic and axillary hair in females; source of estrogen after menopause
Describe the effects of hyper-secretion and hypo-secretion of Gonadocorticoids.
HYPERSECRETION:
Virilization of females (adrenogenital syndrome)
HYPOSECRETION:
No effects known
Describe the regulation of release of Gonadocorticoids.
Stimulated by ACTH
Mechanism of inhibition incompletely understood, but feedback inhibition not seen
Describe the target organs and effects of Gonadocorticoids.
Insignificant effects in males
Responsible for female libido; development of pubic and axillary hair in females; source of estrogen after menopause
Describe the effects of hyper-secretion and hypo-secretion of Gonadocorticoids.
HYPERSECRETION:
Virilization of females (adrenogenital syndrome)
HYPOSECRETION:
No effects known
Describe the regulation of release of Catecholamines;
Stimulated by preganglionic fibres of the sympathetic nervous system
Describe the target organs and effects of Catecholamines.
Sympathetic nervous system target organs: Effects mimic sympathetic nervous system activation; increases heart rate and metabolic rate; increase blood pressure by promoting vasoconstriction
Describe the effects of hyper-secretion and hypo-secretion of Catecholamines.
HYPERSECRETION:
Prolonged fight or flight response; hypertension
HYPOSECRETION:
Unimportant
What arteries does the cortex receive?
Cortex receives short cortical arteries run in parallel with the cords of cells to the medulla
What blood does the medulla receive?
- Medulla receives:
• blood draining from the cortex (containing
adreno-corticosteroids which influence the production of adrenaline by the medullary cells)
• fresh arterial blood in long cortical arteries
Describe the process of the short term stress response.
- Impulses passing through the spinal cord
- Go to preganglionic sympathetic fibres
- Release acetylcholine to nerve endings in medulla
- Stimulates chromatin cells to release catecholamines
Describe the process of the long term stress response.
- Stress occurs for long time
- Stimulates release of CRH from hypothalamus
- Travels down capillary networks down into anterior pituitary
- Binds to corticotrophs cells of anterior pituitary
- This stimulates release of ACTH
- ACTH goes to the adrenal cortex to bind to cells in the zona reticular and fasciculate to stimulate synthesize and release of glucocorticoid (cortisol)
What three inputs do the zona glomerulosa cells respond to?
- ACTH
- Increased plasma potassium (depolarizes plasma membrane)
- Angiotensin II
Describe the process of the short-term stress response.
Impulses passing down through the spinal cord into preganglionic sympathetic fibres release acetylcholine, which goes to nerve endings in the medulla to stimulate chromaffin cells to release catecholamines
Describe the process of the long-term stress response.
If stress occurs for a longer time, it stimulates the release of CRH from the hypothalamus. This travels down capillary networks and down the anterior pituitary. Binds to corticotrophs, stimulating the release of ACTH. ACTH goes to the adrenal cortex to stimulate the release of mineralocorticoids and glucocorticoids.
What are the actions of cortisol?
Stimulate gluconeogenesis in the liver cells (produced enzymes important for it)
Inhibit protein synthesis in the muscle cells
Inhibit lipogenesis in the fat cells
What is the treatment for Addison’s disease?
Glucocorticoid replacement therapy - hydrocortisone administration (25mg in morning, 12.5mg in afternoon)
Intravenous saline infusion if severely dehydrated and condition is life threatening, and administrating of fludrocortisone (mineralocorticoid agonist)
What is the precursor for catecholamines?
L-Tyrosine
What is the action of tyrosine hydroxyls?
Converts L-Tyrosine to L-Dopa
Rate limiting step
What is the action of amino acid decarboxylase?
Converts L-Dopa to dopamine
What is the action of Dopamine B- hydroxylase?
Converts dopamine to noradrenaline
What converts norepinephrine to epinephrine?
Phenylthanolamine-N-methyltransferase
