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Endo > Catecholamines > Flashcards

Catecholamines Flashcards

1
Q

Describe the adrenal medulla

A
  • Only makes up 10-20% of the gland
  • Neuroendocrine tissue
  • Acts as sympatehtic ganglion
  • Embyrologically from autonomic nervous system, neural crest cell origin
  • Secretes catecholamines
  • Axons extend into cortex
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2
Q

Describe the synthesis pathway for epinephrine and norepinephrine

A
  • Begins with phenylalanine
  • Converted to tyrosine
  • Converted to dihydroxyphenylalanine catalysed by tyrosine hydroxylase
  • Then to dopamine
  • Then to norepinephrine
  • Then to epinephrine
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3
Q

What are the sources of epinephrine in the blood?

A

Adrenal medulla only

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4
Q

What are the sources of norepinephrine in the blood?

A
  • Adrenal medulla

- Postganglionic sympathetic neurons

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5
Q

What is the function of continual secretion of catecholamines? Use arterioles as an example

A
  • Basal rates of activity = sympathetic tone
  • E.g. arterioles: sympathetic tone keeps arterioles constricted to 50% of diamete
  • Increase in stimulation leads to more constriction, while decrease leads to less constriction
  • Allows one system to cause both constriction and dilation
  • Careful modulation using one system
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6
Q

Outline the kinetics of catecholamines

A
  • Stored in secretory vesicles and released via exocytosis
  • Circulate freely in blood
  • Metabolised in liver and kidney, short palsma half life (1-3 mins)
  • Urinary exretion of unmetabolised epinephrine and norepinephrine
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7
Q

Why can diseases of the adrenal medulla not be assessed by measuring the level of catecholamines in the blood?

A
  • Constantly excreted and metabolised by liver and kidneys
  • large bursts in sympathetic activity quickly removed
  • Can use breakdown products to give indication of pathology in gland
  • Some factors may be indicative of medullary tumours
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8
Q

Compare the epinephrine and norepinephrine from the arenal medulla as opposed to the nervous system

A
  • Same effect
  • Lasts longer from adrenal medulla
  • Highly responsive
  • More generalised from adrenal medulla
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9
Q

Explain the relationship between teh nervous system and the adrenal medulla

A
  • SNS activated when rapid and large response to stimulus required
  • Pre-ganglionic sympathetic neurones carry action potential to adrenal medulla, stimulate release of catecholamines (via Ach) = large output
  • Adrenal medulla is equivalent to post-ganglionic sympathetic neurone
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10
Q

Describe the adrenergic receptors

A
  • alpha and beta
  • Alpha 1, 2
  • Beta 1, 2, 3,
  • Effector cells can be stimulated or inhibited
  • Different receptors on different cells, thus having different effect
  • Some cells have more than one type, others only one type
  • Allows close modulation of cellular activity
  • e.g cardiomyocytes only have beta-receptors
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11
Q

Describe the effect of catecholamines binding to alpha-receptors

A
  • Vasoconstriction
  • Pupil dilation
  • intestinal relaxation
  • Pilomotor contraction
  • Bladder sphincter contraction
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12
Q

Describe the effect of catecholamines binding to beta-1 receptors

A
  • Increased heart rate

- Increased contractility

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13
Q

Describe the effect of catecholamines binding to beta-2 receptors

A
  • Vasodilation
  • Bronchodilation
  • Glycogenolysis
  • Lipolysis
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14
Q

What are the clinal consequences of SNS activation?

A
  • Pupil dilation
  • Reduced secretions
  • Sweating
  • Increased metabolism
  • Tachycardia
  • General vasoconstriction
  • Tachycardia
  • Increased cardiac output
  • Bronchodilation
  • Decreased gastrointestinal motility
  • Altered metnal state (increased alertness)
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15
Q

What are the intracellular pathways for signal transduction?

A
  • Adenyl cyclase
  • Phospholipase C, PI3, and DAG
  • Ion channels
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16
Q

Describe adenyl cyclase pathway of beta-receptors

A
  • Binding to cell surface protein
  • Activates G-protin
  • Stimulates adenylyl cyclase
  • Generates cAMP
  • Activates protein kinase A
  • Protein phosphorylated
  • Biological response initiated
17
Q

Describe the effects of cAMP

A
  • Catalytic subunit of protein kinase A enters nucleus
  • Binds to cAMP response element binding protein (CREB) and phosphorylates
  • CREB-P binds to CRE and changes genes expression
18
Q

Describe the effects of cAMP in the heart

A
  • Ca2+ channel opening time prolonged
  • Strengthens contractions and increases uptake into SR at end of contraction (shortening contraction)
  • Leads to stronger and more frequent contractions
19
Q

Describe the phospholipase C pathway of alpha adrenoceptors

A
  • Hormone binds to cell surface receptor
  • Activates phospholipase C via G protein
  • Phospholipid PIP2 broekn down to IP3 and DAG
  • DAG activates membrane bound protein kinase C
  • Protein phosphorylated
  • Biological response is increased intracellular Ca2+
20
Q

What does tissue response to catecholamines vary according to?

A
  • Type and density of receptors

- Relative concentrations of epinephrine and norepinephrine locally

21
Q

What is the effect on arterioles in response to catecholamines in
a. the intestines
b. the muscles
and what is the function of this?

A

Intestine: Alpha-receptor stimulates mooth myocytes of blod vessels leading to vasoconstriction

  • Muscles: Beta-2 receptors, inhibits smooth myocytes of blood vessels leading to vasodilation
  • Function of redistribution of blood to where it is needed for fight or flight
22
Q

What are the metabolic effects of catecholamines?

A
  • Increase amount of readily available energy by mobilising glucose and fatty acids
  • Increase glycogenolysis
  • Increase gluconeogenesis
  • Hormone sensitive lipase stimulated
  • TAG hydrolysed
23
Q

Why is it unusual to find normal blood glucose in cats?

A
  • High stress response to sampling
  • Often high glucose due to this
  • Increased catechoamines leading to increased release of glucose from storage molecules
24
Q

What are the metabolic effects of catecholamines combined with in the fight or flight response?

A
  • Increased heart rate and contractility
  • Increased cardiac output and bblood pressure
  • Shift in perfusion to increase central and reduce peripheral
25
Q

Comapre the metabolic and cardiac effects of epinephrine vs norepinephrine

A
  • Epinephrine has 5-10x greater metabolic effect than norepinephrine
  • Epinephrine has greater effect on beta-receptors (and thus cardiac stimulation)
  • Norepinephrine has more profound effect on blood vessels (increases total periphearl resistance and raises blood pressure)
26
Q

Compare the actions of epinephrine and norepinephrine on the blood vessels within muscle

A
  • Epinephrine acts on beta-2-receptors causing casodilation

- Noreprinephrine acts on alpha-receptros causing strong vasoconstriction (shock)

27
Q

What are the main aims fo the SNS?

A

To respond to starvation, shock and facilitate resuscitation

Endo (30 decks)

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