L3: Hypertension: Mechanisms and Consequences

Question 1

What is systemic arterial pressure?

Answer 1

Pressure coming out of left side of heart supplying oxygenated blood to all organs

Question 2

What happens when you have hypertension?

Answer 2

• 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

Question 3

Risk factors for CVD

Answer 3

• 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

Question 4

What are the determinants of mean blood pressure? Equation?

Answer 4

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

Question 5

What is normal mean systemic arterial pressure? systolic? Diastolic?

Answer 5

Mean: 100mmHg
Systolic: 120 mmHg
Diastolic: 90 mmHg

Question 6

What can change CO?

Answer 6

• volume in the system (depends on kidneys) -
• heart: how fast and strong its beating
• nerves and hormones

Question 7

What determines R?

Answer 7

• SNS activity
• hormones
• local factors: O2, pH

Question 8

What causes hypertension?

Answer 8

Increase in CO

increase in Systemic Vascular Resistance (SVR)

Question 9

What determines resistance?

Answer 9

R is proportional to

1. tube length
2. viscosity of fluid

Inversely proportional to
3. radius raised to fourth power

Question 10

r4 factor - relationship btwn radius and resistance

Answer 10

small change in radius of blood vessels = large effect on resistance
- doubling radius increases flow 16x

Question 11

What controls contraction of vascular smooth muscle?

Answer 11

1. Vascular endothelial cells
2. mediators released locally from sympathetic nerve terminals (e.g. noradrenaline)
3. Circulating hormones (e.g. vasopressin, ang II )

Question 12

Equation for CO (cardiac output)

- what affects CO

Answer 12

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

Question 13

What is the role of increased sympathetic activity ?

Answer 13

• 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

Question 14

What do we target to reduce blood pressure?

Answer 14

reduce AngII
reduce sympathetic activities
reduce blood volume
- helps reduce CO and thus BP

Question 15

What happens when Beta adrenergic receptors are stimulated?

Answer 15

Beta adrenergic receptor stimulation causes increased intracellular Ca2+ –> increases force development of heart (more contraction) –> increased SV (stroke volume)

Question 16

What are the determinants of pulse pressure?

- equation

Answer 16

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

Question 17

Aortic pulse pressure - importance of aorta and artery compliance

Answer 17

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

Question 18

What happens to pulse pressure if you have poor compliance and stiff arteries?

Answer 18

larger pulse pressure - high systolic pressure but low diastolic pressure

Question 19

Relationship btwn compliance of aorta and age

Answer 19

Compliance of aorta decreases with age

• pulse pressure increases
• systolic pressure increases + diastolic pressure may decrease

Question 20

Effect of increased stroke volume on arterial pulse pressure

Answer 20

more volume = higher pulse pressure

Question 21

What is SV determined by?

Answer 21

• preload
• afterload
• chronotropy
• inotropy

Question 22

What is diastolic pressure determined by?

Answer 22

Determined by diastolic run off - ability of blood to flow forward
Dependent on:
TPR : increased resistance increases diastolic pressure
HR: increased HR increases DP

Question 23

Recommended lifestyle changes for treatment of hypertension

Answer 23

1. weight reduction
2. moderation of alcohol consumption
3. Diet - high fruit + veges/low fat
4. salt restriction
5. Regular exercise
6. Smoking cessation

Question 24

What drugs affect total TPR?

Answer 24

alpha-adrenergic blockers 
Ang II receptor blockers 
ACE inhibitors 
Ca2+ channel blockers 
Vasodilators (nitrates) 
Diuretics

Question 25

What drugs affect CO?

Answer 25

Beta blockers --> heart rate Diuretics --> preload, total body water --> stroke volume -venous return Beta blockers + Ca2+ channel blockers --> contractility --> SV - venous return

Question 26

What is the ABCD treatment for hypertension?

Answer 26

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

Question 27

Second line treatment for hypertension

Answer 27

- alpha-adrenoreceptor antagonists/ centrally acting sympatholytic agents - K+ channel agonists - Aldosterone antagonist

Question 28

What medicines can increase hypertension?

Answer 28

- NSAIDs and oral contraceptives | - should not be given to hypertensives

Question 29

What are the general 3 steps to treat hypertension?

Answer 29

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)

Question 30

Who should not be prescribed ACE or ARB? What is recommended instead?

Answer 30

- Females of reproductive age should not be prescribed | - INSTEAD beta blockers (e.g. metoprolol) or calcium channel blockers (e.g. felodipine) are recommended

Question 31

When should beta blocker in combination be considered?

Answer 31

Ischaemic heart disease or heart failure present - reduce mortality Atrial fibrillation present - for rate control

Question 32

What medication should be recommended if peripheral vascular disease is present?

Answer 32

ACE inhibitor - to slow disease progression | or Calcium channel blocker - vasodilate peripheral arteries

Question 33

What is role of ACE inhibitors?

Answer 33

- 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

Question 34

Side effects of ACE inhibitors | - what can it be changed to?

Answer 34

Irritable dry cough - particularly in females | - can change to ang II receptor blockers (less side effects)

Question 35

What is the role of calcium channel blockers?

Answer 35

vasodilation - targets blood vessel - targets cardiac muscle

Question 36

When should ACE inhibitor be prescribed first line?

Answer 36

if patient has diabetes or evidence of end organ damage