Hypertension

Question 1

Hypertension is actually a disease of the

Answer 1

Kidney

Question 2

Short term control of blood pressure

Answer 2

Can be modelled in a closed system

Balance between CO and TPR

Question 3

How is short term blood pressure control regulated?

Answer 3

Baroreceptors

Question 4

Where are low pressure baroreceptors located?

Answer 4

Large systemic veins, in the pulmonary arteries, in the walls of the atria, and ventricles of the heart.

Question 5

Where are high pressure baroreceptors located?

Answer 5

Arch of aorta and carotid sinus

Question 6

What are type I high pressure baroreceptors?

Answer 6

Large type A myelinated afferent fibers.

Lower activation thresholds and fire more rapidly upon stimulation.

Question 7

What are type II high pressure baroreceptors?

Answer 7

Unmyelinated or small poorly myelinated type C afferent fibers.

Higher activation thresholds and discharge at lower frequencies.

Question 8

Which high pressure baroreceptors are responsive to both increases and decreases in arterial pressure?

Answer 8

Carotid sinus

Question 9

Which high pressure baroreceptors are responsive to only an increase in pressure?

Answer 9

Aortic arch

Question 10

How do baroreceptors signal in response to a rise in blood pressure?

Answer 10

Stretches the wall of the blood vessel, triggering the baroreceptors.

Firing of afferents (glossopharyngeal nerve via carotid sinus nerve from the carotid body and vagus nerve from aortic bodies).

These afferents project to the cardiovascular nuclei in the medulla (NTS), this acts to effectively inhibit the sympathetic input

Efferent projections are then sent via the ANS (parasympathetic fibres - vagus nerve) which act to reduce the heart rate and cardiac contractility - reducing blood pressure.

Question 11

How do baroreceptors respond to a fall in blood pressure?

Answer 11

Decreased arterial pressure: is detected by baroreceptors

Decreased firing rates then trigger a sympathetic response, sympathetic is no longer inhibited.

This stimulates an increase in heart rate and cardiac contractility leading to an increased blood pressure.

Question 12

What cant baroreceptors act long term?

Answer 12

Mechanism of triggering baroreceptors resets itself once a more adequate blood pressure is restored.

When changes in pressure are sustained for several minutes, baroreceptors are reset
rapidly and the baroreceptor pressure-activity curve
shifts in the direction of pressure change to function at a new set point.

Question 13

What happens to the baroreceptor reflex in hypertensives?

Answer 13

Baroreceptors are impaired in chronic hypertension and are said to become chronically reset. This is characterized by elevations in pressure threshold and decreases in baroreceptor activity

Question 14

Why is it good baroreceptors can reset?

Answer 14

This allows baroreceptors to buffer fluctuations of arterial pressure effectively because the new pressure set point remains on the steep portion of the reset pressure-activity curve

Question 15

How did Guyton challenge the cardiocentric view of BP?

Answer 15

Guyton successfully coupled the venous return and circulation to the cardiac output.

Question 16

How did Guyton challenge the vasculocentric view?

Answer 16

Added circulatory volumes and compliances to initial considerations of CO and TPR and linked them to sources of fluid entry (absorption of salt and water by the digestive tract) and loss (chiefly salt and water excretion by the kidney).

Question 17

What is the pressure-natriuresis relationship?

Answer 17

Renal perfusion pressure can directly regulate sodium reabsorption in the proximal tubule.

If BP rises, so too does renal arterial pressure (RAP) and the kidney responds by increasing sodium excretion and reducing ECFV; the converse applies if blood pressure falls.

Question 18

What is the set point blood pressure in terms of PN?

Answer 18

Set-point BP is the point at which ECFV (extracellular fluid volume) and PN (pressure-natriuresis) are in equilibrium.

Question 19

Theoretically why should we not get hypertension?

Answer 19

PN (pressure natriuresis) should offset completely any change in BP

Question 20

What modulates PN?

Answer 20

RAAS (acts as a confounder to pure PN)

Question 21

Are RAAS and PN both needed for long term pressure regulation?

Answer 21

Yes

Question 22

What is theorised to underpin hypertension?

Answer 22

Whatever the cause of hypertension, it must in the end somehow modify the kidney’s ability to excrete salt and water for a given BP; otherwise, the hypertension would lead to an increased excretion of salt and water through the PNR, ultimately returning BP to regular levels.

Therefore PN curve changes - pushed to the right (higher pressure for same Na+ excretion) and the gradient of the slope can also be blunted

Question 23

Halls dog experiments show that

Answer 23

The kidney sets an arterial pressure that depends markedly upon sodium excretion, probably revealing innate renal function (PN) devoid of its normal fine endogenous neuroendocrine regulation (RAAS).

Hypertensives have higher perfusion threshold to produce the same urine.

Question 24

Why is hypertension an disease of the kidney?

Answer 24

A change in BP can only be sustained if the acute PN response is impaired, making hypertension a disease of the kidney.

Question 25

What are the perceived causes of hypertension?

Answer 25

Genetic predisposition to hypertension (kidney differences, PN differences, Ang II sensitivity)

Chronic raise in Sympathetic innervation

Epigenetic factors may affect the abundance of renal sodium transporters or the regulation of the PN response by angiotensin II

Inflammation

Abnormal renin-angiotensin ratio, a variant of Conn’s syndrome (primary hyperaldosteronism)

Question 26

What are risk factors for hypertension?

Answer 26

Age (old age)

Ethnicity: higher rates in non-white ethnicities

Question 27

Why is age a risk factor for hypertension?

Answer 27

Structural changes in the arteries and especially with large artery stiffness.

Increased inflammation and ROS production in old age

Renin secretion decreases with age

Question 28

Why is ethnicity a risk factor?

Answer 28

Black people with hypertension commonly have threonine to methionine substitution in the EnaC channel (T594M), contributes to low renin hypertension

Lower nephron mass, reduced renin secretion.

Question 29

Plasma sodium in a patient with excess ADH secretion

Answer 29

125mM