The Adrenal Gland and Adrenal Hormones Flashcards
Role of aldosterone
- maintains water and electrolyte balance
- ADH regulates osmolarity due to effect on free water balance
Integrated systems for regulating salt/water balance
- Aldosterone acts in distal tubule of kidney, causing sodium retention
- ADH responds to thirst
- Responds to low blood pressure and high potassium by causing an increase in secretion of aldosterone
Synthesis of aldosterone
- adrenal cortex synthesises aldosterone from cholesterol
- no storage pool -> limited by rate at which glomerulosa cells can synthesise the hormone
- ACTH, extracellular K, Na and peptide hormone AngII stimulate production of aldosterone in glomerulosa cell
- enhance secretion by increasing activity of enzymes acting at rate-limiting steps in aldosterone synthesis
Mechanism of action of aldosterone
- stimulate kidney to absorb sodium and water and enhance potassium secretion
- similar actions in colon, salivary glands, and sweat glands
- aldosterone regulates only a small fraction of sodium reabsorption occuring in distal tubule
- loss of aldosterone-mediated reabsorption can result in significant electrolyte abnormalities, including life-threatening hyperkalemia and hypotension
- excess aldosterone secretion produces hypokalemia and hypertension
Points of aldosterone action
- increase transcription of Na-K pump, augmenting distal sodium reabsorption
- increase expression of apical sodium channels and an Na/K/Cl cotransporter, so increasing sodium reabsorption and potassium secretion
Proteins involved in sodium transport
- ROMK; extrudes potassium
- ENaC; moves sodium into cell
- SGK inhibits system targeting ENaC channel for degradation
Regulation of aldosterone synthesis
- sodium and water levels feedback through the RAS
- high extracellular K
- ACTH
Feedback through the RAS
- AngII binds to receptor
- G alpha q to PLC to DAG and IP3
- calcium increase, calcium-dependent enzymes increase
- depolarise glomerulosa cells
- voltage-gated calcium channels open
- calcium rises, stimulating production of P450scc, delivery of cholesterol, and alsodterone synthase
High extracellular potassium
- depolarises glomerulosa cells
- voltage-gated calcium channels open
- intracellular calcium rises, stimulating production of P450scc, delivery of cholesterol, and aldosterone synthase
ACTH regulation in aldosterone synthesis
binds to MC2R to stimulate calcium influx
Development of the adrenal cortex
from mesodermal cells into steroidogenic cells
How is the medulla formed
neural crest-derived chromaffin cells migrate into the corticol cells to form the medulla
Influence of cortisol on development of adrenal gland
- chromaffin cells have the potential to develop into postganglionic sympathetic neurons and synthesise the norepinephrine from tyrosine
- cells of the medulla are exposed to high local concentrations of cortisol which inhibits neuronal differentiation
- cortisol induces expression of PNMT in chromaffin cells, which converts norepinephrine to epinephrine - the primary hormonal product of the adrenal medulla
Synthesis of catecholamines
- Tyrosine is converted to dihydroxyphenylalanine by tyrosine hydroxylase
- DOPA is converted to dopamine by amino acid decarboxylase
- dopamine is converted to norepinephrine by sympathetic stimulation of dopamine beta-hydroxylase
- norepinephrine is converted to epinephrine by cortisol + PNMT
Synergy between CRH/ACTH/cortisol and sympathetic epinephrine axis
results in cortisol release, sustaining the epinephrine response
How are epinephrine and norepinephrine stored in chromaffin granules
complexed with adenosine triphosphate (ATP), calcium and proteins called chromogranins
Regulation of catecholamines
- inhibitory feedback mechanisms involving norepinephrine
- inhibits acetylcholine release from the presynaptic alpha2 receptors
- inhibits tyrosine hydroxylase activity when present in high concentrations
Degradation of catecholamines
- very brief
- two primary enzymes involved: MAO or COMT
Mechanism of action of catecholamine alpha 1 receptor
- increased IP3, DAG
- acts on vascular smooth muscle
- epinephrine < norepinephrine
Mechanism of action of catecholamine alpha 2 receptor
- decrease cAMP
- acts on pancreatic beta cells
- epinephrine < norepinephrine
Mechanism of action of catecholamine beta 1 receptor
- increase cAMP
- act on heart tissue cells
- epinephrine = norepinephrine
Mechanism of action of catecholamine beta 2 receptor
- increase cAMP
- act on liver tisues
- epinephrine»_space; norepinephrine
Mechanism of action of catecholamine beta 3 receptor
- increase cAMP
- adipose tisues
- norepinephrine»_space; epinephrine
Physiologic actions of catecholamines
- increased blood flow to the muscles
- increased glucose availability
- decreased energy demand by visceral smooth muscle
Increased blood flow to the muscles
- norepinephrine and epinephrine (beta1) act on the heart to increase the rate and strength of contractions
- induce cardiac output
Increased glucose availability
- epinephrine promotes glycogenolysis in muscle (beta2)
- exercising reduces free fatty acids
- epinephrine and norepinephrine (beta 2 and 3) promote lipolysis in adipose tissue
- increases levels of lactate and glyceril
- increases blood glucose by increasing hepatic glycogenolysis and gluconeogenesis
Pheochromocytoma
- uncommon tumor caused by hyperplasia of adrenal medulla or other chromaffin tissue
- excessive, unregulated production of catecholamines
- symptoms: hypertension, headaches, sweating, anxiousness, tremor, glucose intolerance
