52.1 The Control of Systemic Arterial Blood Pressure

Question 1

What provides short-term regulation for arterial blood pressure?

Answer 1

Baroreceptor reflex
circulation as a closed system

Question 2

Describe the receptors, ganglia and afferent nerves involved in the baroreflex.

Answer 2

Carotid sinus baroreceptors:

• Via the petrosal ganglia
• Glossopharyngeal nerve (IX)

Aortic arch baroreceptors:

• Via the nodose ganglia
• Vagus nerve (X)

Question 3

What type of receptors are involved in the baroreflex?

Answer 3

Baroreceptors -> These detect transmural pressure, not flow

Question 4

What are the atrial baroreceptors?

Answer 4

↑-pressure receptors in carotid sinus + aortic arch
*Innervated by glossopharyngeal/ vagus nerve respectively

Question 5

What are the cardiopulmonary baroreceptors?

Answer 5

↓-pressure receptors in atria + adjacent large veins.

Question 6

What does stimulation of the low pressure baroreceptors lead to?

Answer 6

Triggers secretion of ADH, angiotensin and aldosterone (increase salt and water reabsorption in the kidney to raise BP)

Question 7

Where do the afferent nerves of the baroreflex synapse in the brain?

Answer 7

Nucleus tractus soltarius (NTS) -> This is in the medulla

Question 8

Describe the efferent target organs of the baroreflex.

Answer 8

Parasympathetic:

• Heart

Sympathetic:

• Heart
• Blood vessels
• Kidney

Question 9

Is the normal stability of ABP independent or dependent of local flows to organs and tissues?

Answer 9

It is independent of local flows to organs and tissues.

Question 10

How is ABP regulated in the long term?

Answer 10

By renal pressure natriuresis (sodium excretion) and diuresis (water loss) to keep blood volume at 5L with circulation as an open system.

Question 11

What is Guyton’s hypothesis/ physical equilibrium model?

Answer 11

Guyton’s hypothesis → ↑ renal perfusion pressure → ↑ Na+ excretion → ↑ water loss → ↓ ECF → ↓ BP

Question 12

What is the mechanism of Guyton’s hypothesis?

Answer 12

Mechanism unclear → 2 hypotheses:
*↑ renal perfusion → ↑ GFR + Tubular flow rate → ↓ time for water/ Na+ reabsorption → ↑ excretion.
*↑ renal perfusion pressure → ↑ shear stress → ↑ NO production → ↑ medullary washout

Question 13

Which system is in control of long term blood pressure regulation?

Answer 13

Renin-angiotensin-aldosterone axis (RAAS)

Question 14

What is typical blood pressure?

Answer 14

120/80mmHg

Question 15

Which blood pressure is defined as being hypertensive?

Answer 15

Three consecutive readings of over 140/90 at home (monitored 24 hours at home where two readings are taken every day)

Question 16

What are the BP targets for those > 80, and <80?

Answer 16

• <140/90 mmHg in patients aged <80
  *<150/90 in patients aged ≥ 80

Question 17

How can hypertension be classified?

Answer 17

1o → essential HT (95%)
*Heterogeneous disease
*Precise + ultimate causes undetermined despite multiple genetic, hormonal, nervous, + environmental factors + lifestyle linked to HT.
2o → 5%. Known cause
*Renal disease (e.g. renal stenosis/ diabetic nephropathy)
*Endocrine disorders (e.g. Conn’s syndrome - 1o hyperaldosteronism/ Cushing’s disease - pituitary adenoma → ↑ ACTH → ↑ cortisol)

Question 18

What are type 1 and type 2 HT according to NICE?

Answer 18

*Type 1 HT
<55 y/o
associated w ↑ renin levels + vasoconstriction
*Type 2 HT
>55y/o or African-Caribbean family origin
associated w/ ↓ renin levels + ↑ circulating volume

Question 19

What is the first and second line treatment in hypertension to someone under 55 or a diabetic?

Answer 19

1) ACE inhibitor
2) Calcium channel blocker (amlodipine)
LOWERS TOTAL PERIPHERAL RESISTANCE

Question 20

What is the first and second line treatment for hypertension in someone who is over 55 or black and not diabetic?

Answer 20

1) Calcium channel blocker (amlodipine)
2) Thiazide like diuretic

Question 21

What are the other treatments that can be used alongside the specific first and second line treatments for hypertension?

Answer 21

USED AFTER FIRST AND SECOND LINE
Beta blockers
alpha blocker
spironolactone (antagonist of aldosterone receptor to stop increased reabsorption of sodium)

Question 22

What are the risk factors for hypertension? Why?

Answer 22

*Age: ↑ age → ↑ stiffness of arterioles → ↓ vascular compliance. Also nephron count ↓ w/ age → p-n curve shifted to right.
*Obesity: ↑ sympathetic activity
*Lifestyle: smoking/ alcohol
*Ethnicity: African-Caribbean heritage at ↑er risk (lower nephron count? Substitution in ENaC?)
*↑er Na+ intake
*Genetic: rare, some linkage analyses in familial HT have identified some rare monogenic HT causes
Genes associated w/ essential HT include ACE polymorphisms, AT-1 receptor gene, etc.

Question 23

How can you tell if someone has end organ damage as a result of hypertension?

Answer 23

ECG hypertrophy (enlarged QRS wave)
Looking at the back of the eye (haemorrhage of retinal blood vessels)

Question 24

Give an example of a tumour which can cause hypertension?

Answer 24

Pheochromocytoma

Question 25

How does pheochromocytoma lead to hypertension?

Answer 25

- Phaeochromocytoma = tumour of chromaffin cells in the adrenal medulla --> significantly increased circulating levels of adrenaline and other catecholamines -This can be severe enough to push the body into a hypertensive crisis, where blood pressure becomes so high (often >200mmHg systolic) as heart cannot effectively pump blood against the dramatically elevated systemic resistance (vascular smooth muscle responding to α1 stimulation, dramatic stimulation of tachycardia and positive inotropy) --> crashing organ perfusion for significant damage to multiple systems if not treated with adrenergic antagonists such as prazosin, and diuretics to help reduce blood pressure over time

Question 26

Why do individuals with Conn's syndrome often have a high blood pressure?

Answer 26

Conn's is caused by the overproduction of aldosterone, causing increased salt and water retention

Question 27

How does blood pressure change with age?

Answer 27

A reasonable approximation is: * Healthy systolic pressure increases linearly with age * Healthy diastolic pressure rises between the age of 20 and 50 and then progressively declines.

Question 28

What classifies as hypertension?

Answer 28

According to NICE, hypertension is confirmed when a patient has: * Clinic blood pressure of 140/90 mmHg or higher **and** * ABPM daytime average or HBPM average of 135/85 mmHg or higher (these are measures of blood pressure throughout the day)

Question 29

What are the benefits and disadvantages of treating hypertension?

Answer 29

The benefits of treatment are due to the fact that hypertension is associated with other diseases: * Stroke (both haemorrhagic and embolic) * Heart attack * Heart failure * Renal disease * Retinal disease The disadvantages are that hypertension itself is usually asymptomatic and treatment often has side effects.

Question 30

Describe the changes in the cardiovascular system that lead to hypertension.

Answer 30

* Remember: BP = SVR x CO * It has been observed that patients with pre-hypertension typically have a high cardiac output but normal systemic resistance * However, in patients with hypertension, there is usually normal cardiac output but increased systemic resistance * Thus, it has been suggested that the first event in the pathophysiology is usually an increase in cardiac output * This results in an increased ratio of wall : lumen in systemic blood vessels, to combat the change in wall stress * This leads to an increase in systemic vascular resistance (Note: This might be controversial)

Question 31

What are the main afferent pathways that feed into the brain and are involved in cardiovascular control (aside from the baroreceptors in the aortic arch and carotid sinus)? [IMPORTANT]

Answer 31

* Cardiopulmonary receptors * In great veins, pulmonary artery and right atrium/ventricle * Detect filling of the heart * Inhibit heart rate and cause vasodilation, plus increased renal excretion -\> Causing blood pressure and volume to fall * Arterial baroreceptors * In aortic arch and carotid sinus * Detect arterial pressure * Inhibit heart rate and cause vasodilation -\> Causing blood pressure to fall * Muscle work receptors * Involve C fibres that are activated upon muscle activity (e.g. by potassium) * Increase heart rate -\> Causing blood pressure to rise * Arterial chemoreceptors * In aortic arch and carotid sinus * Respond to decreased pO₂ and pH, and increased pCO₂ * Increase heart rate and sympathetic stimulation of vasculature -\> Causing blood pressure to rise

Question 32

When is the only time that the cortex of the brain is involved in the cardiovascular system?

Answer 32

It is indirectly involved via fainting. When you are shocked/scared by something, there is a massive drop in the vagus activity, so that blood pressure drops very much and you may faint.

Question 33

How does renal perfusion affect natiuresis?

Answer 33

Higher perfusion leads to higher salt excretion.

Question 34

How is the left ventricle affected in hypertension?

Answer 34

* The left ventricle has a thick wall, and so it is dependent on the coronary arteries and their transmural branches for its oxygen supply. * The blood flow in these vessels is at its greatest during diastole, when the ventricular wall is relaxed and not compressing the coronary arteries. * In hypertension, the left ventricle hypertrophies to overcome the increased resistance. * This increases the risk of myocardial ischaemia for two reasons: * Decreased perfusion of the left ventricle since the wall compresses the coronary arteries * Increased metabolic demand of the heart to overcome the systemic resistance (Note that this ventricular hypertrophy is not the same as ventricular dilation, which occurs when the ventricle cannot clear all of its blood in systole, so that it remains partly filled. If the ventricular hypertrophy leads to ischaemia, both may occur simultaneously.)

Question 35

How are arteries affected in hypertension?

Answer 35

* There is a bidirectional causal relationship between hypertension and atherosclerosis: * Hypertension increases the risk of atherosclerosis (due to increased turbulence of blood flow) * Atherosclerosis increases the risk of hypertension (due to reduced elasticity of the wall) * There is a similar bidirectional relationship between hypertension and arterial wall thickening, where the muscular arterial wall thickens to sustain the increased pressure, which in turn leads to increased blood pressure due to reduced elasticity

Question 36

What kind of hypertension is most common in the elderly and why? [IMPORTANT]

Answer 36

* Isolated systolic hypertension -\> This is where the systolic pressure is classed as high, but diastolic is normal or even low. * This is commonly seen among the elderly as there is increased deposition of calcium and collagen to the arterial wall, which reduces the compliance of the arterial vessels, decreased lumen-to-wall ratio, and increased thickening and fibrotic remodeling of the vascular intima and media.

Question 37

When the body wants to change blood flow to a certain tissue, does the ABP change? [IMPORTANT]

Answer 37

No, it remains relatively constant. It can be seen as a reservoir of driving force, which can be distributed locally to different tissues by local regulation.

Question 38

What are the two main types of hypertension? [IMPORTANT]

Answer 38

* Primary hypertension (a.k.a. 'essential hypertension') -\> Hypertension with an unknown underlying cause * Secondary hypertension -\> Hypertension with a known disease causing it

Question 39

Give some factors that the spec says are associated with long-term increases in blood pressure. [IMPORTANT}

Answer 39

* ‘Essential hypertension’ -\> Unknown cause * Renal disease * Phaeochromocytoma -\> Rare tumor of adrenal gland tissue. It results in the release of too much epinephrine and norepinephrine.

Question 40

What is the relationship between the radius of a blood vessel and its resistance?

Answer 40

R ∝ 1/r⁴

Question 41

Juxtaglomerular cells are modified ... cells.

Answer 41

Smooth muscle

Question 42

Describe the mechanism of renin secretion.

Answer 42

This is unusual because the calcium is an inhibitor of release.

Question 43

How does the macula densa influence renin secretion from the juxtaglomerular cells?

Answer 43

* When there is reduced sodium detected by the macula densa, renin secretion is stimulated. * Prostaglandins are used to stimulate release * Adenosine is used to inhibit release

Question 44

List and describe the consequences associated with hypertension?

Answer 44

-Left ventricular hypertrophy --> ischemia --> angina --> MI (coronary atery perfusion reduced as the wall is too thick too allow proper relaxation and filling) -Stroke (haemorrhaigic or embolic-athersclerotic plaque) -Renal damage due to stenosis of smaller arterioles or fibrosis of nephrons following shear stress here -Atherosclerosis due to increased turbulence and endothelial damage --> inflammatory response -Arterial aneurysm -Retinal damage from haemorrhage of blood vessels F

Question 45

What are the potential treatments for hypertension?

Answer 45

LIFESTYLE CHANGE: increased exercise, weight loss, dietary manipulation (limit salt and cholesterol intake) DRUG THERAPY

Question 46

Draw and reference a graph to show the relative risk of mortality (from CHD and stroke) according to arterial blood pressure. [IMPORTANT]

Answer 46

(Lipp, 2015)