L3: Hypertension: Mechanisms and Consequences Flashcards
What is systemic arterial pressure?
Pressure coming out of left side of heart supplying oxygenated blood to all organs
What happens when you have hypertension?
- increased wall tension
- too much sympathetic activity and Ang II
- remodelling of heart: thicker, stiffer wall, smaller lumen
- poor supply to end organs - heart needs to work harder
- increase in afterload, arterial damage
Risk factors for CVD
- Asymptomatic w no known risks - 1st screening M 45 yrs, F 55 yrs
- High risk (genetics or co-morbidities) - 1st screening M 35yr, F 45 yr
BP > 170/100 mmHg - treat regardless
Total CVD risk is 10>20% - treatment options, initiate lifestyle changes
Total CVD risk > 20% - strongly recommend BP lowering treatment
What are the determinants of mean blood pressure? Equation?
P = CO (cardiac output) x R (peripheral resistance)
CO: total blood flow
- determined by tissue/body needs
R: increasing total R leads to upstream increase in pressure to maintain flow
If CO increases, resistance must decrease to maintain arterial pressure
What is normal mean systemic arterial pressure? systolic? Diastolic?
Mean: 100mmHg
Systolic: 120 mmHg
Diastolic: 90 mmHg
What can change CO?
- volume in the system (depends on kidneys) -
- heart: how fast and strong its beating
- nerves and hormones
What determines R?
- SNS activity
- hormones
- local factors: O2, pH
What causes hypertension?
Increase in CO
increase in Systemic Vascular Resistance (SVR)
What determines resistance?
R is proportional to
- tube length
- viscosity of fluid
Inversely proportional to
3. radius raised to fourth power
r4 factor - relationship btwn radius and resistance
small change in radius of blood vessels = large effect on resistance
- doubling radius increases flow 16x
What controls contraction of vascular smooth muscle?
- Vascular endothelial cells
- mediators released locally from sympathetic nerve terminals (e.g. noradrenaline)
- Circulating hormones (e.g. vasopressin, ang II )
Equation for CO (cardiac output)
- what affects CO
CO = HR x SV
- increasing HR = increases CO
- increasing preload (filling of heart) = increases CO
- increasing afterload (arterial pressure) = increases CO
- increased sympathetic activity or Ca2+ availability = increases contractility and thus SV
What is the role of increased sympathetic activity ?
- send info from brain to heart to contract more
- increased heart CO
- act on kidney : constrict blood vessels and secrete renin –> increase AngII –> increase blood volume –> increase CO
What do we target to reduce blood pressure?
reduce AngII
reduce sympathetic activities
reduce blood volume
- helps reduce CO and thus BP
What happens when Beta adrenergic receptors are stimulated?
Beta adrenergic receptor stimulation causes increased intracellular Ca2+ –> increases force development of heart (more contraction) –> increased SV (stroke volume)
What are the determinants of pulse pressure?
- equation
Pulse pressure (PP) = systolic pressure (Ps) - diastolic pressure (Pd)
Systolic pressure - depends on aortic compliance + SV
Diastolic pressure - depends on aortic compliance + diastolic run off:
Heart rate, TPR
Aortic pulse pressure - importance of aorta and artery compliance
Systole: aorta stretches to absorb blood
Diastole: flow continues due to compliance (elastic recoil) of blood vessels
More compliant large blood vessels = smaller pulse pressure
Compliance of arteries - ensure capillary flow continues throughout cardiac cycle
Once reaching small arterioles = flow is non-pulsatile
What happens to pulse pressure if you have poor compliance and stiff arteries?
larger pulse pressure - high systolic pressure but low diastolic pressure
Relationship btwn compliance of aorta and age
Compliance of aorta decreases with age
- pulse pressure increases
- systolic pressure increases + diastolic pressure may decrease
Effect of increased stroke volume on arterial pulse pressure
more volume = higher pulse pressure
What is SV determined by?
- preload
- afterload
- chronotropy
- inotropy
What is diastolic pressure determined by?
Determined by diastolic run off - ability of blood to flow forward
Dependent on:
TPR : increased resistance increases diastolic pressure
HR: increased HR increases DP
Recommended lifestyle changes for treatment of hypertension
- weight reduction
- moderation of alcohol consumption
- Diet - high fruit + veges/low fat
- salt restriction
- Regular exercise
- Smoking cessation
What drugs affect total TPR?
alpha-adrenergic blockers Ang II receptor blockers ACE inhibitors Ca2+ channel blockers Vasodilators (nitrates) Diuretics
What drugs affect CO?
Beta blockers –> heart rate
Diuretics –> preload, total body water –> stroke volume -venous return
Beta blockers + Ca2+ channel blockers –> contractility –> SV - venous return
What is the ABCD treatment for hypertension?
A: angiotensin pathway: ACE inhibitors or Angiotensin type 1 receptor blockers
B: beta blockers (via effect on HR/CO) –> NOT recommended as first choice as they dont reduce risk of stroke and are poorly tolerated
- not targeting vasculature that causes stroke only target heart
- only for pregnant women or people with heart failure
C: calcium channel blockers
D: diuretic (thiazide)
- caution in diabetics
Second line treatment for hypertension
- alpha-adrenoreceptor antagonists/ centrally acting sympatholytic agents
- K+ channel agonists
- Aldosterone antagonist
What medicines can increase hypertension?
- NSAIDs and oral contraceptives
- should not be given to hypertensives
What are the general 3 steps to treat hypertension?
Step 1: for primary prevention in patients w uncomplicated hypertension = ACE inhibitor or Calcium channel blocker
Step 2: combine ACE inhibitor or ARB with Calcium channel blocker
Step 3: Add thiazide diuretic e.g. indapamide
(targets kidneys)
Who should not be prescribed ACE or ARB? What is recommended instead?
- Females of reproductive age should not be prescribed
- INSTEAD beta blockers (e.g. metoprolol) or calcium channel blockers (e.g. felodipine) are recommended
When should beta blocker in combination be considered?
Ischaemic heart disease or heart failure present - reduce mortality
Atrial fibrillation present - for rate control
What medication should be recommended if peripheral vascular disease is present?
ACE inhibitor - to slow disease progression
or Calcium channel blocker - vasodilate peripheral arteries
What is role of ACE inhibitors?
- reduce production of AngII (vasoconstrictor)
- reduces vasoconstriction
- acts on kidneys to reduce sodium retention - reduce blood volume
- act on heart long term –> prevent remodeling of heart
Side effects of ACE inhibitors
- what can it be changed to?
Irritable dry cough - particularly in females
- can change to ang II receptor blockers (less side effects)
What is the role of calcium channel blockers?
vasodilation
- targets blood vessel
- targets cardiac muscle
When should ACE inhibitor be prescribed first line?
if patient has diabetes or evidence of end organ damage
