Session 5: Control of Blood Pressure - The Patient with Hypertension

Question 1

Define hypertension.

Answer 1

A sustained increase in blood pressure. Blood pressure is measured mmHg.

Question 2

What is a normal range of blood pressure?

Answer 2

90/60 to 120/80 mmHg.

Question 3

What is stage 1 hypertension?

Answer 3

140/90 mmHg

Question 4

What is stage 2 hypertension?

Answer 4

160/100 mmHg

Question 5

What is severe hypertension?

Answer 5

>180 systolic >110 diastolic

Question 6

What is primary hypertension?

Answer 6

It is also called essential hypertension. 95% of cases are primary hypertension and the cause is unknown.

Question 7

What is hypertension where the cause is known called? Give examples.

Answer 7

Secondary hypertension. E.g. Renovascular disease Chronic renal disease Hyperaldosteronism Cushing’s syndrome

Question 8

Explain how hypertension can have impact on organs and tissues.

Answer 8

Hypertension leading to an increase in afterload which can lead to left ventricular hypertrophy and subsequent heart failure. Or an increase in afterload can lead to an increase in myocardial oxygen demand and therefore myocardial ischaemia and myocardial infarction. Hypertension can also lead to arterial damage -> atherosclerosis and weakened vessels. Atherosclerosis and weakened vessels can lead to: Cerebrovascular disease stroke Aneurysm Nephrosclerosis and renal failure Retinopathy

Question 9

Give examples of target organ damage and where to do physical examination.

Answer 9

Brain, eyes, heart (ECG), kidneys (listen, feel and test urine), arteries by palpating all peripheral arteries and checking for abdominal aneurysm.

Question 10

How is mean arterial blood pressure calculated?

Answer 10

MAP = CO x TPR but also by: MAP = 1/3 SBP + 2/3 DBP

Question 11

How is cardiac output calculated?

Answer 11

CO = SV x HR

Question 12

How is the blood pressure regulated short term?

Answer 12

By baroreceptors found in the carotid sinus and aortic arch. They respond to the stretching of said vessels resulting in sensory nerves sending signals to the medulla oblongata to cause vasodilation and and bradycardia in order to counteract the increased mean arterial pressure.

Question 13

Why is baroreceptors only effective in short term regulation?

Answer 13

Because they will adapt and reset to a higher level if the high blood pressure is sustained.

Question 14

Give examples of medium and longer term control of blood pressure.

Answer 14

Interaction of neurohumoral responses that are directed at controlling the sodium balance and therefore also the extracellular fluid volume. The control of the extracellular fluid volume controls the plasma volume. This means that when sodium increases in blood stream the plasma volume will increase as water follows.

Question 15

Give the names of the four parallel neurohumoral pathways that control circulating plasma volume and therefore also BP.

Answer 15

1. Renin-angiotensin-aldosterone system 2. Sympathetic nervous system 3. Antidiuretic hormone (ADH) 4. Atrial natriuretic peptide (ANP) The first three raise blood pressure if they are stimulated. The last one decreases blood pressure if stimulated.

Question 16

Where is renin released from?

Answer 16

From granular cells of the juxtaglomerular apparatus also known as JGA. Renin is released from the granular cells of the afferent arteriole in response to reduced perfusion pressure.

Question 17

Give three factors that stimulate renin release.

Answer 17

Reduced NaCl delivery to the distal tubule Reduced perfusion pressure in the kidney that is detected by baroreceptors in afferent arteriole Sympathetic stimulation to JGA

Question 18

What is the role of renin?

Answer 18

Renin is an enzyme that converts angiotensinogen to angiotensin 1.

Question 19

Explain the angiotensinogen pathway.

Answer 19

Angiotensinogen -> angiotensin 1 by renin -> angiotensin 2 by ACE (angiotensin converting enzyme) Angiotensin 2 is the effective hormone that causes vasoconstriction etc.

Question 20

What are the roles of angiotensin 2 and what receptors does it act on?

Answer 20

Angiotensin 2 acts on two types of Ang 2 receptors called AT1 and AT2 which both are GPCRs. They main action however is via the AT1 receptor.

Question 21

Give sites where AT receptors can be found and what the actions of stimulation are.

Answer 21

Arterioles - Vasoconstriction Kidneys - Stimulates Na+ reabsorption at the kidney. Sympathetic NS - Increased release of NA Adrenal cortex - Stimulates release of aldosterone Hypothalamus - Increases thirst sensation (ADH release)

Question 22

What are the actions of aldosterone?

Answer 22

Acts on principal cells of collecting ducts Stimulates Na+ and hence water reabsorption Activates apical Na+ channels like ENaC and apical K+ channels Also increases basolateral Na+ extrusion via Na/K - ATPase All of this increases blood pressure.

Question 23

Angiotensin converting enzyme also called ACE has another name and another function than converting angiotensin 1 to angiotensin 2. What is that role?

Answer 23

It is also called kininase 2 and breaks down bradykinin into peptide fragments. Bradykinin is a vasodilator so ACE therefore further increases vasoconstriction by breaking down bradykinin.

Question 24

How can you counteract the function of angiotensin 2 and the breakdown of bradykinin to decrease blood pressure?

Answer 24

By ACE inhibitors which will inhibit the formation of angiotensin 2 and will also inhibit the breakdown of bradykinin.

Question 25

How does the sympathetic nervous system regulate blood pressure?

Answer 25

High levels of sympathetic stimulation reduce renal blood flow. This causes vasoconstriction of the arterioles and a decrease in glomerular filtration rate which will subsequently decrease Na+ excretion. It activates apical Na/H+ exchanger and basolateral Na/K - ATPase in proximal convoluting tubule. It also stimulates renin release from JGA which will then lead to an increase in Ang 2 and aldosterone levels causing Na+ reabsorption.

Question 26

How does ADH regulate blood pressure?

Answer 26

Formation of concentrated urine by retain water to control plasma osmolality. Stimulates Na+ reabsorption by acting on thick ascending limb and stimulating apical Na+/K+/Cl- co-transporter Also causes vasoconstriction

Question 27

What is ADH release stimulated by?

Answer 27

Increase in plasma osmolarity and severe hypovolaemia.

Question 28

How does natriuretic peptides regulate blood pressure?

Answer 28

Promotes Na+ excretion. Causes vasodilation of afferent arterioles. Increased blood flow increases glomerular filtration rate. It also inhibits Na+ reabsorption.

Question 29

What regulates natriuretic peptide release? How is it released?

Answer 29

It is synthesised and stored in atrial myocytes and released from atrial cells in response to stretch as low pressure volume sensors in the atria sense it.

Question 30

What happens to ANP when circulating volume is low?

Answer 30

ANP release is inhibited to increase BP.

Question 31

What is the role of prostaglandin in BP control?

Answer 31

Acts as a vasodilator and important when levels of Ang 2 are high. Means it lowers blood pressure.

Question 32

What is the role of dopamine in BP control?

Answer 32

Fomed locally in kidneys from circulating L-DOPA. Causes vasodilation and increases renal blood flow. Reduces reabsorption of NaCl. Means it lowers blood pressure.

Question 33

Explain the complication and treatments of renal artery stenosis.

Answer 33

Renal artery stenosis causes a fall in perfusion pressure in the affected kidney. This means that the body thinks that the BP is too high and not getting there although that is not the problem. In response renin production is increased and eventually forms Ang 2 which causes vasoconstriction and Na+ retention of the other kidney. It will therefore increase blood pressure even though that wasn't a problem to begin with. It is treated by surgery - fixing the renal artery stenosis.

Question 34

Explain renal parenchymal disease.

Answer 34

Can be due to a loss of vasodilator substances. In later stage Na+ and water retention is due to inadequate glomerular filtration. This means that it is a volume-dependent hypertension.

Question 35

Give adrenal causes of secondary hypertension.

Answer 35

Conn's syndrome Cushing's syndrome Tumour of the adrenal medulla.

Question 36

Explain Conn's syndrome.

Answer 36

It's an aldosterone secreting adenoma that causes hypertension and hypokalaemia.

Question 37

Explain Cushing's syndrome.

Answer 37

Excess secretion of glucocorticoid cortisol. At high concentration it acts on the aldosterone receptors causing Na+ and water retention.

Question 38

Explain tumour of the adrenal medulla (phaeochromocytoma)

Answer 38

Secretion of catecholamines which are NA and adrenaline.

Question 39

Give non-pharmacological approaches to treat hypertension.

Answer 39

Exercise Diet Reduced Na+ intake Reduced alcohol intake

Question 40

How do you treat hypertension by targeting the renin-angiotensin-adlosterone system?

Answer 40

By ACE inhibitors which prevents the production of Ang 2 from Ang 1. Also by Ang 2 (AT1/AT2) receptors antagonists. This means that blocking the production or action of Ang 2 has a diuretic and vasodilator effect.

Question 41

Give examples of pharmacological vasodilators.

Answer 41

Verapamil and Nifedipine which are L-type channel blockers that reduce entry of ca2+ into vascular smooth muscle causing dilation. Alpha 1 receptors blocker like Doxazosin which reduces sympathetic tone and vasodilation.

Question 42

Explain how to treat hypertension with diuretics.

Answer 42

Thiazide e.g. which reduces circulating volume and also BP. It inhibits Na/Cl- cotransporter on apical membrane of cells in distal tubule. There are other diuretics as well which acts as aldosterone antagonists such as spironolactone which also lowers BP.

Question 43

What is a less common treatment of hypertension?

Answer 43

Beta-blockers.

Question 44

Explain how beta-blockers are used as treatment for hypertension.

Answer 44

They are not very common and not used in hypertension alone. They work by inhibiting b1 receptors in the heart reducing heart rate and contractility -\> reduce in BP. Would only be used if there are other indications such as previous MI.

Question 45

So to briely outline: Which are the most common antihypertensives?

Answer 45

ACE inhibitors, renin inhibitors, aldosterone antagonists, alpha-blockres, diuretics and beta-blockers.

Question 46

Label the diagram.

Answer 46