Flashcards in 5. Control of BP Deck (24):
How is BP calculated? How is mean arterial BP calculated?
1. BP = CO x TPR
(CO = HR x SV)
2. maBP = diastolic pressure + 1/3 pulse pressure
(PP = SP - DP)
What is the normal range for heart rate?
What is the normal range for BP?
HR: 60-100 bpm
BP: 90/60 - 140/90 mmHg
Define tachycardia and bradychardia.
tachycardia = resting HR >100 bpm
bradychardia = resting HR <60 bpm
Which system regulates acute change in BP?
What does the baroreceptor reflex act on to regulate BP?
1. adjust sympathetic and parasympathetic inputs to the heart to alter CO (affects both SV and HR)
2. adjust sympathetic input to peripheral resistance vessels to alter TPR
What are baroreceptors?
Nerve endings in the carotid sinus and aortic arch which are sensitive to stretch. .
- increased arterial pressure stretches these receptors
- decreased pressure reduces receptor stretch
How does the CNS detect increased BP?
1. Baroreceptors in carotid sinus and aortic arch are stretched by increased arterial BP.
2. Stimulate cardiovascular centre in medulla obloganta via afferent glossopharyngeal nerves.
How does the CV control centre respond to an increased BP?
1. Increases parasympathetic output via vagus nerve... more ACh released at mAChRs of SAN... decreased HR... decreased CO... decreased BP.
2. Decreases sympathetic output... less NA released... reduced activation of:
i) alpha Rs on arteriorlar SM... vasodilation... decreased TPR... decreased BP.
ii) beta1 Rs on ventricular myocardium... decreased inotropy... decreased CO... decreased BP.
iii) beta1 Rs in SAN... decreased HR... decreased CO... decreased BP.
How does NA act to increase BP?
1. NA binds to beta1 R... alpha subunit of Gs dissociates... activates adenylyl cyclase.
2. AC converts ATP to cAMP...
i) binds to R subunits of PKA in cardiac myocytes... enhances calcium currents (release from SR and extracellular influx) and calcium sensitivity... increased inotropy.
ii) activates funny currents in SAN... speeds up pacemaker potential... increased chronotropy.
Why are baroreceptors not able to control long term changes in BP?
Threshold for baroreceptor firing resets to a higher level if BP elevated for prolonged time.
Which mechanisms regulate medium and long term BP?
4 parallel neurohumoral pathways control circulating plasma volume and hence BP:
i) renin-angiotensin-aldosterone system
ii) sympathetic nervous system
iii) antidiuretic hormone (ADH)
iv) atrial natriuretic peptide (ANP)
Which organ is responsible for controlling plasma volume and how does it do so?
Kidneys, by controlling sodium reabsorption:
increased Na+ reabsorption increases water reabsorption... increases plasma volume... increases CO and BP.
Which cells release renin? Which factors stimulate this release?
Granular cells of juxtaglomerular apparatus (JGA = macula densa + granule cells + surrounding mesangial cells) in the kidney
1- reduced NaCl delivery to macula densa of distal tubule
2- sympathetic stimulation of JGA
3- reduced perfusion pressure in kidney (sensed by renal baroreceptors)
Describe the production of angiotensin II by the RAAS.
1. Renin (released by kidney) converts angiotensinogen (released by liver) to angiotensin I.
2. ACE (released from lungs) converts angiotensin I to angiotensin II.
What are the actions of angiotensin II?
Binds to AT1 and AT2 GPCRs (main actions via AT1) at:
1. arterioles - vasoconstriction
2. kidney - stimulates Na+ reabsorption
3. sympathetic NS - increased NA release (+ve feedback)
4. hypothalamus - stimulates ADH release... increases thirst sensation
5. adrenal cortex - stimulates aldosterone release
What are the actions of aldosterone?
Acts on principal cells of kidney collecting ducts:
i) activates apical Na+ channel (ENaC) - stimulates Na+ (and therefore water) reabsorption
ii) activates Na/K/ATPase - increases basolateral Na+ extrusion
Why is hypokalaemia a clinical sign of high aldosterone levels?
Aldosterone activates apical K+ channels as well as Na+ channels - promotes extrusion of K+.
As well as converting AngI to AngII, what is the effect of ACE (aka kininase II)?
breaks down the vasodilator bradykinin - augments the vasoconstriction effects of AngII
How does the sympathetic NS regulate long term BP?
High levels of sympathetic stimulation...
1- arteriole vasoconstriction (decreased kidney perfusion)... reduce renal blood flow (GFR)... decreased Na+ excretion.
2- activates apical Na+/H+ exchanger and basolateral Na+/K+ ATPase in PCT.
3- stimulates renin release from JGA.
How does antidiuretic hormone (ADH, aka arginine vasopressin) regulate long term BP? What stimulates ADH release?
ADH release stimulated by increases in plasma osmolarity or severe hypovolaemia.
1. Increases water reabsorption in distal nephron (AQP2) - forms concentrated urine to control plasma osmolarity.
2. Stimulates apical Na/K/Cl co-transporter in thick ascending limb - stimulates Na+ reabsorption.
How does ANP regulate long term BP?
Acts in opposite direction to other neurohumoral regulators:
1. vasodilation of afferent arteriole... increased renal blood flow... increased GFR
2. inhibits Na+ reabsorption along nephron
What promotes ANP release?
- Synthesised and stored in atrial myocytes - released in response to stretch of atrial low pressure volume sensors.
- Reduced effective circulating volume (i.e. reduced heart filling and stretch) inhibits the release of ANP, to increase BP.
What is the function of prostaglandins in BP? Why can these not be used as anti-hypertensive medication?
- Act as LOCAL vasodilators:
1) PGE2 enhances GFR and reduces Na+ reabsorption - effect in BP decrease.
2) buffer to excessive vasoconstriction produced by SNS and RAAS (may have important BV protective function, esp when high levels of AngII).
- Very short 1/2 life and only active locally - would have to be used IV to have any clinical effect.