Adrenal Physiology Flashcards
What are the 4 layers of the adrenal gland?
Glomerulosa
Fasciculata
Reticularis
Medulla
What does the zona glomerulosa mainly secrete?
Mineralocorticoids primarily aldosterone for the kidneys
What does the zona fasciculata mainly secrete?
Glucocorticoids - cortisol and corticosterone to most cells for glucose and glycogen formation
What does the zona reticularis mainly secrete?
Androgens to skin, bones and other tissues
What does the adrenal medulla secrete?
Epinephrine and Norepinephrine to most cells
What is the adrenarche?
Maturation of zona reticularis in late childhood associated with increased adrenal androgen (DHEA/DHEAS) secretion
What is adrenopause?
Decline in DHEA production with age
Where does adrenocorticoid synthesis take place?
ER and mitochondria
What does enzyme deficiency alter?
Production of ALL adrenocorticoids
What does the zone glomerulosa secrete?
Aldosterone
What increases aldosterone secretion?
Angiotensin II and K+
What are the zona glomerulosa actions mediated by?
Mineralocorticoid receptor
What is the role of aldosterone?
Maintenance of electrolyte balance and ECF/plasma volume
Regulates naturesis in renal distal tubule and collecting ducts
Role in acid/base balance
What are the causes of Conn’s Syndrome?
Aldosterone secreting adrenal tumour
Adrenal hyperplasia
How does Conn’s Syndrome affect the renal electrolyte and H2O absorption?
Electrolyte imbalances (hypernatremia and hypokalemia)
metabolic alkalosis
water retention
low plasma free calcium level
What does hypernatremia and hypokalemia cause in Conn’s Syndrome?
Hypern - muscle cramps (neuronal hyperexcitability)
Hypok - muscle weakness (muscle hypo excitability)
What is the treatment for Conn’s SYndrome?
Surgery
Spironolactone (aldosterone receptor antagonists)
What is Addison’s Disease?
Autoimmune destruction of adrenal cortex
What does Addison’s disease cause?
Glucocorticoid (mineralcorticoid) deficiency
Hypoaldosteronism
cardiac arrythmias and low ECF volume
What are two characteristics of the Zona Fasiculata?
Pale cells - numerous lipid droplets
Well developed ER and plentiful mitochondria
What does the Zona Fasiculata synthesize?
Cortisol
ACTH
Lesser amounts of androgen/estrogen synthesis
What are the Zona Fasiculata actions mediated by?
Glucocorticoid receptor
What are the 4 metabolic actions of the glucocorticoids (cortisol and ACTH)?
Increase muscle protein catabolism
Increase triglyceride breakdown
Increase hepatic gluconeogenesis
Decrease muscle insulin sensitivity
What is cortisol’s effect on immunity and inflammation?
Suppress immune and inflammatory response
Inhibit T and B cell function
Inhibit cytokine production
What is cortisol’s effect on vasculature?
Maintains normal BP and CO
What is cortisol’s effect on water and electrolyte balance?
Antidiuretic actions (promotes H2O reabsorption)
Increases Na+ reabsorption and K+ excretion
What is cortisol’s effect to stress?
Metabolic and vascular actions considered beneficial
What is the circadian rhythm?
Suprachiasmatic nucleus in hypothalamus that is entrained by visual and light/dark cues
Cortisol and ACTH levels increase at night
What are 4 causes of Cushing’s Syndrome (hypercortisolism)?
Cortisol secreting tumours
Ectoptic tumours secreting ACTH
Pituitary ACTH excess (Cushings Disease)
Prolonged glucocorticoid therapy
What are 3 symptoms relating to metabolic actions of cortisol?
Hyperglycemia/glucosuria
Insulin resistance
Obesity
purple stripes
females (amenorrhea and hirstusim)
What is Addison’s Disease (hypocortisolism)?
Autoimmune destruction of adrenal cortex
What are the symptoms of Addison’s Disease?
Glucocorticoid (and mineralcorticoid) deficiency
Hypocortisolism
What does hypocortisolism cause?
Hypoglycemia
ACTH excess
MSH excess (hyperpigmentation)
What is the difference between cortisol and aldosterone binding?
Cortsiol has equal affinity for glucocorticoid and mineralcorticoid receptors
Aldosterone only binds to mineralcorticoids
What is the role of HSD11b2 in mineralcorticoid receptors?
Minimizes illicit activation of mineralocorticoid receptor by cortisol
Where is HSD11b1 highly active?
Most metabolically active tissues
When is the zona reticularis fully differentiated?
At early childhood (6-8 years old)
What does the zona reticularis secrete?
Adrenal androgen/estrogen synthesis
DHEA
Estrone and estradiol
What regulates secretion from the Zona Reticularis?
ACTH (not pituitary gonadotrophins)
What is the role of DHEA?
Development of secondary sexual characteristics in females
Development of male genitalia in pre-pubertal boys
What is congenital Adrenal Hyperplasia?
Defective adrenal steroidogenesis
21-beta-hydroxylase deficiency
What 4 endocrine disturbances does congenital Adrenal Hyperplasia cause?
Lowers cortisol production
Lowers mineralocorticoid production
increases male sex steroids
increases ACTH
What are 3 other symptoms of congenital Adrenal Hyperplasia?
Adrenal hyperplasia
Mineralocorticoid deficiency (salt-wasting form)
Aberrant development of primary/secondary sex characteristics
What is the adrenal medulla derived from?
Neural crest of embryonic ectoderm
What is a nerve ganglion?
Cluster of neural bodies outside CNS
What are chromaffin cells?
Neuroendocrine cells that are modified postganglionic sympathetic neurons
What do chromaffin cells release?
Epinephrine that acts as a hormone
Norepinephrine (20%)
Adrenergic receptors
What are chromaffin cells innervated by?
Preganglionic sympathetic neurons
What triggers chromaffin cells?
Increases sympathetic nervous sytem activity
How does endocrine epinephrine differ to sympathetic effects?
Lasts 5-10x longer
Affects a wider range of cell types
What receptors do E and NE act via?
Plasma membrane adrenoreceptors - G protein coupled adrenergic receptors
What allows for tissue specificity and multiplicity of action for E and NE?
Multiple receptor subtypes
differential ligand binding affinities
different tissue distribution
What do the alpha receptors prefer?
NE (more involved in neural pathways)
What do beta receptors prefer?
Epinephrine and increases cyclic AMP
What are 4 effects of epinephrine?
Increases HR and CO
Increases breakdown of Glycogen and fat
Increases O2 consumption
Increases skeletal muscle flow
What is the role of epinephrine in the stress response?
Blood flow diverted to vital organs
Increase in HR, peripheral resistance and strength
Increase gluconeogenesis and glycogenolysis
What does a tumour of the chromaffin cells cause?
Severe hypertension
Hyperglycemia
Increased metabolic rate
arrhythmias
anxiety
