Patho & Treatment - Hypertension

Question 1

Define hypertension (HTN)

Answer 1

Persistently elevated systolic and diastolic BP equal to or greater than 140/90mmHg.
Or
Pre-hypertension of 120+/90+ mmHg
On 3 separate occasions or 24hr ambulatory records

Question 2

Define pre-hypertension

Answer 2

Any BP consistently higher than target but below the HTN range i.e. 120+/90+ mmHg

Question 3

Does BP naturally increase with age?

Answer 3

No. This is a myth. The incidence and prevalence of HTN increases with age

Question 4

What are the main causes of HTN?

Answer 4

90% of HTN cases are due to lifestyle choices
10% are due to secondary HTN (i.e. to a non-lifestyle related pathology e.g. tumours in the adrenal medualla which lead to a lot of release of sympathetic hormones into the blood, drugs - corticosteroids, renal disease

Question 5

What are the consequences of HTN?

Answer 5

1. Endothelial damage –due to high shearing forces on the endothelial wall, (nitric oxide) NO deficit & atheroma formation. NO is a vasodilator and it prevents myocardial ischaemia
2. Risk of aneurysm formation & rupture (secondary to congenital weakness e.g Marfans or infective episode e.g streptococcal infection or salmonella etc..)
3. Risk of organ damage (heart, kidneys & eyes - blindness/visual loss)
4. Premature death

Question 6

What conditions does HTN increase the risk of developing?

Answer 6

Increases risk of AMI or CVA by 2 -fold

Question 7

Do younger people get HTN?

Answer 7

Yes.
6% of under 25 year olds have HTN
25% of 35 year old have HTN

Question 8

What could explain the fact that HTN is lower in white populations than in black and south Asian populations?

Answer 8

Increase in BMI causes an increase in systolic and diastolic BP

Subcutaneous fat and visceral adipose fat (which inflames the organs)

Question 9

What causes obesity?

Answer 9

Diet
Lack of physical activity - leading to an increase in visceral and subcutaneous adipose tissue
Smoking - increases sympathetic N.S. activity
High salt intake - retentions salt and therefore water which increases blood pressure

Question 10

Outline the mechanism of how obesity-induced hypertension occurs

Answer 10

Adipocytes increase in size & number with increase in BMI. Adipocytes release leptin into the blood. Leptin is the satiety hormone, it travels to the brain to turn off appetite. Receptors in the brain become resistant to leptin. A high amount of leptin is then produced to try and activate these receptors
SNS is switched on due to the high volumes of leptin. SNS increases HR & SV which increases CO & BP.
SNS acts on the arteries causing vasoconstriction of which increases TPR which increase HTN

Adipocytes release (angiotensin 2) ACE2 into the blood which increases BP through its ability to vasoconstrict blood vessels. ACE2 stimulates release of aldosterone (ALD). ALD acts on kidneys to conserve Na & H20, blood volume is pushed up and hence blood pressure rises

Adipocytes release cytokines into the systemic circulation & cause an inflammatory reaction on arteriole endothelial walls which is the beginning of atheroma formation. Cytokine-induced inflammation cause endothelial cells to have reduced ability to produce NO which means arteries have less ability to vasodilator, so they are vasoconstricted which pushes up TPR and BP

The cytokines-induced inflammation increase endothelin 1 (a vasoconstrictor) production is increased (in arterioles)

Breakdown of adipocytes cause increase in free fatty acids into the circulation reactive oxygen species (ROS)

Question 11

How does the CVS respond to hypertension i.e. what are the pathological responses to hypertension?

How would you fix these pathological responses?

Answer 11

1. VAT (visceral adipose tissue) -driven HTN is characterised by sustained neuro-endocrine response i.e. an increased and abnormal activation of the SNS and the
   RAAS (which perpetuates HTN)
2. Chronic elevation of angiotensin 2 and aldosterone which drive structural remodelling of arteries (this perpetuates hypertension)
3. Aided by NO depletion and increased production of endothelin 1

Switch off/down-regulate the neuro-endocrine responses - mainly angiotensin 2 and remove the underlying causes of this precipitating neuroendocrine dysfunction i.e. unhealthy lifestyle choices driving VAT accumulation

Question 12

Outline the vascular remodelling/structural changes that occur within the blood vessel due to HTN

Answer 12

1. Inflammation
2. Increased production of collagen - vessel becomes stiff and non-compliant
3. Increased calcification of smooth muscle - vessel loses its distensibility
4. Smooth muscle hypertrophy - which narrows the lumen and increases resistance, TPR and BP

Question 13

What happens to BP on exercise?

Answer 13

After exercise SNS is switched off and systolic blood pressure falls off
In hypertensive individuals BP remains lower than before exercise. This can remain low for up to 12hr. It is called post-exercise hypotensive period

Question 14

Why is BP lower at the end of exercise and why does it last for up to 12hr?

Answer 14

1. Due to short-time down-regulation of activity in the SNS and in the vasomotor centre, arterioles are in a more vasodilated state
2. Less catecholamines
3. Lower levels of ACE2 & endothelin (both vasoconstrictors)
4. Increased levels of circulating NO
5. Increased sensitivity of baroreceptors in the carotid sinus of the heart (baroreceptors is to reduce BP, in HTN baroreceptors become inactivated)

Question 15

What drugs decrease blood volume (for the treatment of HTN)? Give a name, ending and example.

Answer 15

Diuretics - ending: semide, e.g. furosemide

ACE inhibitors - decrease angiotensin and aldosterone. Ending: - pril, e.g. Ramipril, fosinopril

SARAs (selective aldosterone antagonists) ending: - one e.g. spirinolactone, eplerenone

ARBs (angiotensin receptor blockers) ending: sartan, e.g. losartan

Question 16

What physiological parameters would cause hypertension to decrease?

Answer 16

Lower TPR, CO and blood volume

Question 17

What drugs decrease cardiac output (for the treatment of HTN)? Give a name, ending and example.

Answer 17

beta-blockers - ending: olol, e.g. Bisoprolol, Proprolol

Ca2+ antagonists - ending: dipine, e.g. Amlodipine, felodipine

Question 18

What drugs decrease total peripheral resistance (for the treatment of HTN)? Give a name, ending and example.

Answer 18

Arterial dilators

ACE inhibitors - decrease angiotensin & aldosterone
- pril, Ramipril

ARBs - angiotensin receptor blockers -
-sartan, e.g. losartan

Question 19

Why should someone with HTN exercise?

What type of exercise lowers BP?

Answer 19

24hr reduction in BP with aerobic exercise
Aerobic mainly but dynamic and static resistance training also helps
Daily exercise produces a sustained lower blood pressure and also encourages a reduction in VAT

Question 20

What are the ACSM guidelines for aerobic and strength training?

Answer 20

F: 5-7 times per week
I: Moderate intensity (40 - 60% VO2R//%HRR)
T: Ideally 30mins daily
T: 2-3 times/week strength training
1-3 sets, 8-12 reps, 8-10 muscle groups

Question 21

What type of hypertension do most people have and what are the causes of it?

Answer 21

Primary hypertension

Genetic (ethnicity), lifestyle (bottle-feeding, alcohol, lack of exercise, salt, fats/BMI), obesity, diabetes