Week 19: Monitoring and Control of Blood Pressure Flashcards
What controls arterial blood pressure?
CO
Total peripheral resistance (TPR)
Blood volume
What regulates arterial blood pressure?
Neuronal mechanisms (short-term) Hormonal mechanisms (long-term)
What is a baroreceptor?
pressure sensitive receptors
Relay info to the brain (afferent)
Why are baroreceptors important?
sense blood pressure and relay the info to the brain so proper bp can be maintained
Where are baroreceptors located?
located in the carotid sinus and in the aortic arch
What happens when a baroreceptor detects a change in blood pressure?
projects nerve fibres to the brain stem cardiovascular centre.
What does the baroreceptor reflex consist of? (5) in order
- A detector- BaroR
- Afferent pathways
- A co-ordinating centre
- Efferent neural pathways –> relay output of coordinating centre to the periphery
- Effectors –> execute and appropriate response and alter the controlled variable, correcting deviation form set point.
What is hypotension?
low blood pressure
–> background AP has fallen at baroreceptor
What is hypertension?
High blood pressure
background firing rate at baroreceptors increase
From where does the firing come from in a baroreceptor reflex and where doe sit report to?
Frequency of firing in the baroR from aortic arch and carotid sinus that report to the cardiovascular centre in the brain where the ongoing second to second bp is.
What section does the baroR discharge AP?
systole –> normotensive
What causes cyclic changes in neuronal activity?
cardiac contraction and relaxation
What is the effect of the co-ordinating centre in the BaroR Reflex?
– in the CNS. Compares signal detected in the periphery to a set-point and generates an error message
What can decrease increased bp?
bradycardia and vasodilation
What do the efferent neurones effect?
heart an vessels
Why do we feel light-headed when we stand up?
the alpha-adrenoR present in smooth muscle of lower limb drops when we lie down and drop transiently when we stand up
What is the effect of the afferent nerves when heart rate is increased from the baroreceptor?
increased AP frequency in response to increased bp
Where does the AP from the carotid sinus and aortic arch?
cardiovasular centre in the medulla
What pathway will the medulla decrease its activity when bp is high?
sympathetic
What pathway will the medulla increase activity when bp is high?
parasympathetic nerve
What neurone inhibits the sympathetic pathway when bp is high?
inhibitory interneurone
What organ is innervated by 2 nerves in response to a baroreceptor reflex?
heart via symp and para nerves
What is the name of the parasympathetic receptor on the heart?
M2 AChR
What is the name of the sympathetic receptor on the heart?
beta-1 ADR
What 3 other factors are effected by the sympathetic pathway?
Arterioles
Veins
Kidney
What receptor doe the sympathetic neurone effect on the 3 other organs/vessels?
Arterioles alpha-ADR
Veins alpha-ADR
Kidney beta-ADR
What happens to the heart when baroR detects high BP?
decreased CO
release of ACh increased
release of NA decreased
What happens to the arterioles and the veins when the baroR detects high BP?
reduces release of NA
relaxation
How does the heart slow down? via parasympathetic neurone
ACh released from the post ganglionic fibres of parasympathetic system
Release of ACh to SA node of the atria activates M2AChR
–> slow discharge rate of the AP from SA node = BRADYCARDIA
How does the heart slow down? via sympathetic neurone
NorA from post-ganglionic neurone decreases
As NorA increases the frequency of firing AP (beta-1
How does the sympathetic decrease BP via the arterioles?
decrease norA, reduces contractile response of norA on arterioles
decrease total peripheral resistance, bp falls
How does the sympathetic neurone decrease BP via the veins?
decrease release of NA
decrease alpha-1 ADR stimulation
decrease bp
via frank starling mechanism
How does the sympathetic neurone decrease bp via the kidney?
reduce stimulation of beta1 ADR
decrease the release of renin –> decrease bp = vasodilation
What are the important ways which blood flows to the brain and myocardium(heart)?
via carotid arteries at the carotid sinus) via aorta (aortic arch) respectively
What vessels contain the pressure blood pressure sensors in their walls?
carotid arteries
aorta
What type of receptor is the baroreceptor?
mechanoreceptors
sensitive ion channels
How do the vessel walls activate the baroR?
by stretch not directly by pressure
What nerve do carotid afferents travel along?
sinus nerve the thence the glossopharyngeal (cranial IX) nerve to the cardiovascular centre in the medulla.
What nerve do the aortic arch afferents travel?
vagus (cranial X) nerve
What are baroreceptors the terminals of?
myelinated and unmyelinated sensory fibres that express cation-selective ion channels activated by stretch.
What happens when the baroreceptor terminals open?
generate a graded receptor potential that causes action potential generation which has both dynamic and static components
Why are the baroreceptors specifically located in the aortic arch and carotid sinus?
located in key feeder vessels that supply blood to the organs which are essential to survival of the organism
What effects the response of the mechanosensitive ion channel?
large channel in bp = large change in stretch = large receptor P or depolarisation at the BR terminal
What 2 phases can the baroR response be divided into?
dynamic and static
How can we describe the receptor potential?
frequency modulated signal- frequencey of AP discharge in the BR proportional to blood pressure
What is the dramatic sustained and maddest sustained pressure figures?
DS= 125 mmHg MS= 75 mmHg (less firing)
What makes up the dynamic component of the arterial bp curve?
when systole occurs
What make sup the static component of the arterial bp curve?
when diastole occurs
What can lower the MAP (mean arterial blood pressure) of the blood?
when background firing rate of the BR is lower
When does BR activity cease?
very low pressure (40-60 mmHg)
What is RAAS?
Renin Angiotensin Aldosterone System
What does RAAS play a major role in the regulation of?
- sodium excretion and thus blood volume
- vascular tone directly and indirectly
What releases renin?
kidney- granule cells of the juxtaglomerular apparatus of the kidney
What is renin?
a proteolytic enzyme released from granule cells of the juxtaglomerular apparatus of the kidney in response to the above stimuli, and others
What activates RAAS?
reduction in blood volume and the associated drop in arterial blood pressure
Where is renin released to?
systemic circulation, acting as a hormone
What is renin released in response to?
-Renal sympathetic nerve activity (increased)
-Renal perfusion pressure (decreased)
-Glomerular filtration
(decreased)
What is angiotensinogen?
plasma α2-globulin synthesised and released by the liver
What releases angiotensinogen?
liver
What happens when Renin is released form the kidney and angiotensinogen is released by the liver?
enzyme renin coverts angiotensinogen to angiotensin I
Where is the enzyme ACE expressed?
angiotensin converting enzyme
expressed on the surface of endothelial cells (membrane bound)
When does Angiotensin I come into contact with ACE?
as blood passes through the pulmonary circulation
What does ACE convert Angiotensin I to?
Angiotensin II
vasoconstrictor
When is renin activated?
when blood pressure is low!!
What receptor does angiotensin II bind to and activate?
AT1receptor (GPCR)
How does renin increase [MABP]?
Contraction of vascular smooth muscle due to:
- Activation of smooth muscle AT1 R
- Increased release of noradrenaline form sympathetic nerves innervating vessels
How does renin increase [blood volume and MABP]?
1) Cell growth in the heart and arteries
2) Aldosterone
secretion from adrenal cortex –> Tubular Na+
reabsorption and salt retention
What does ACE do to Bradykinin?
Inactivates bradykinin (vasodilator)
What does the effect of ACEIs do to the activation of Bradykinin (potent vasodilator) ?
inhibits ACE to covert bradykinin to its inactive form
ACCUMULATES IN THE ALVEOLI CAUSING A COUGH
What is an example of a ACEI?
Lisinopril
What is the effect of Lisinopril?
block the conversion of angiotensin I to angiotensin II
What 2 molecules can block the effects of renin?
Angiotensin Converting Enzyme Inhibitors (ACEIs) and Angiotensin I (AT1) Receptor Blockers (ARBs)
What is the effect of ARBs?
AT1 receptor antagonists (‘sartans’ e.g. Losartan) – block the agonist action of angiotensin II at AT1 receptors in a competitive manner
What is an example of a renin inhibitor not recommended with ARB or an ACEI?
ALISKIREN
What are the physiological effects of ACEIs?
- Cause venous dilatation (decrease preload) and
- Arteriolar dilatation (decrease afterload and decrease TPR)
- ->decreasing arterial blood pressure and cardiac load
How do you calculate mean arterial bp?
MABP = CP x TPR
What is aldosterone?
a steroid hormone produced by the adrenal cortex
ACEIs cause reduced level of aldosterone’s, what are the effects of this?
decrease in circulating levels of aldosterone promotes loss of Na+ and H2O
How does ACEIs effect blood pressure? for normal and hypertensive subjects…
Cause a small fall in mean arterial blood pressure in normal subjects, much larger effect in hypertensive patients (especially if renin secretion is enhanced – e.g. as a consequence of diuretic therapy)
What are the adverse effects of ACEIs?
- May initially cause hypotension – especially in patients also treated with diuretics
- Dry cough (probably due to accumulation of bradykinin in the lungs)
- Hyperkalaemia (elevated plasma K+ concentration)
- Angioedema (painful swelling of tissues involving blood vessels)
What is an example of a Angiotensin 1 receptor blocker? (ARBs)
Sartans
What is the difference between ACEIs and ARBs?
ARBs do not inhibit the metabolism of bradykinin
What hypotensive drug should people who get a cough from ACEIs use instead?
ARBs
What are 3 clinical uses of ACE inhibitors and AT1 receptor antagonists? (ACEIs and ARBs)
- HYPERTENSION –>benefit derives from:
1) reduced TPR and MABP and
2) possible suppression of proliferation of smooth muscle cells in the media of resistance vessels in the long-term - CARDIAC FAILURE –> is associated with inappropriate activation of the RAAS. ACEIs
1) decrease vascular resistance improving perfusion;
2) increase excretion of Na+ and H20;
3) cause regression of left ventricular hypertrophy.
-Following myocardial infection infraction –> cardiac failure
