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Reg Phys and Pharm > The Adrenal Gland and Adrenal Hormones > Flashcards

The Adrenal Gland and Adrenal Hormones Flashcards

1
Q

Role of aldosterone

A
  • maintains water and electrolyte balance
  • ADH regulates osmolarity due to effect on free water balance
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2
Q

Integrated systems for regulating salt/water balance

A
  • 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
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3
Q

Synthesis of aldosterone

A
  • 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
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4
Q

Mechanism of action of aldosterone

A
  • 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
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5
Q

Points of aldosterone action

A
  • 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
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6
Q

Proteins involved in sodium transport

A
  • ROMK; extrudes potassium
  • ENaC; moves sodium into cell
  • SGK inhibits system targeting ENaC channel for degradation
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7
Q

Regulation of aldosterone synthesis

A
  • sodium and water levels feedback through the RAS
  • high extracellular K
  • ACTH
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8
Q

Feedback through the RAS

A
  • 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
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9
Q

High extracellular potassium

A
  • depolarises glomerulosa cells
  • voltage-gated calcium channels open
  • intracellular calcium rises, stimulating production of P450scc, delivery of cholesterol, and aldosterone synthase
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10
Q

ACTH regulation in aldosterone synthesis

A

binds to MC2R to stimulate calcium influx

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11
Q

Development of the adrenal cortex

A

from mesodermal cells into steroidogenic cells

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12
Q

How is the medulla formed

A

neural crest-derived chromaffin cells migrate into the corticol cells to form the medulla

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13
Q

Influence of cortisol on development of adrenal gland

A
  • 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
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14
Q

Synthesis of catecholamines

A
  • 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
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15
Q

Synergy between CRH/ACTH/cortisol and sympathetic epinephrine axis

A

results in cortisol release, sustaining the epinephrine response

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16
Q

How are epinephrine and norepinephrine stored in chromaffin granules

A

complexed with adenosine triphosphate (ATP), calcium and proteins called chromogranins

17
Q

Regulation of catecholamines

A
  • inhibitory feedback mechanisms involving norepinephrine
  • inhibits acetylcholine release from the presynaptic alpha2 receptors
  • inhibits tyrosine hydroxylase activity when present in high concentrations
18
Q

Degradation of catecholamines

A
  • very brief
  • two primary enzymes involved: MAO or COMT
19
Q

Mechanism of action of catecholamine alpha 1 receptor

A
  • increased IP3, DAG
  • acts on vascular smooth muscle
  • epinephrine < norepinephrine
20
Q

Mechanism of action of catecholamine alpha 2 receptor

A
  • decrease cAMP
  • acts on pancreatic beta cells
  • epinephrine < norepinephrine
21
Q

Mechanism of action of catecholamine beta 1 receptor

A
  • increase cAMP
  • act on heart tissue cells
  • epinephrine = norepinephrine
22
Q

Mechanism of action of catecholamine beta 2 receptor

A
  • increase cAMP
  • act on liver tisues
  • epinephrine&raquo_space; norepinephrine
23
Q

Mechanism of action of catecholamine beta 3 receptor

A
  • increase cAMP
  • adipose tisues
  • norepinephrine&raquo_space; epinephrine
24
Q

Physiologic actions of catecholamines

A
  • increased blood flow to the muscles
  • increased glucose availability
  • decreased energy demand by visceral smooth muscle
25
Q

Increased blood flow to the muscles

A
  • norepinephrine and epinephrine (beta1) act on the heart to increase the rate and strength of contractions
  • induce cardiac output
26
Q

Increased glucose availability

A
  • 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
27
Q

Pheochromocytoma

A
  • 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

Reg Phys and Pharm (16 decks)

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