W2: Hypertension

Question 1

What are the 3 layers of blood vessels and describe them briefly

Answer 1

Tunic Externa: layer of loose, thick connective tissue which has elastic and collagen fibres. It has a supporting function.

Tunica media:
(External elastic lamina: provides recoil to arteries)
circular layer of Smooth Muscle: controls vessel diameter

Tunica intima:
(internal elastic lamina - only in larger arteries)
lamina propria
basement membrane
Endothelial cell: flattened, thin layer which allows blood to flow smoothly.

Question 2

what are 2 important functional properties of arteries ?

Answer 2

Their elasticity and contractility - comes from elastic tissue

Question 3

What are the 3 types of arteries? give examples

Answer 3

Elastic arteries: large and bendy, they propel high pressure blood out of the heart. e.g. aorta, common carotid, common iliac, subclavian

Muscular arteries: are less bendy (less elastic fibres and more smooth muscle), Smooth muscle allows them to contract to maintain blood pressure further away from the heart. They are distributing arteries since they repeatedly branch. e.g. radial, ulnar, , femoral, axillary.

Arterioles: resistance vessels which branch not capillaries

Question 4

Describe some differences between veins and arteries?

Answer 4

Arteries: thickest layer is the tunica media, small lumens

Veins: thickest layer is tunica adventitia, large lumens

Question 5

What is the cell type found in endothelium?

Answer 5

Simple squamous

Question 6

What do large veins usually have?

Answer 6

Valves to prevent back flow of blood

Question 7

Define blood pressure

Answer 7

The hydrostatic pressure of blood exerted against the walls of a blood vessel or heart chamber.

Question 8

What is systolic blood pressure?

Answer 8

The maximum arterial pressure resulting from the ejection of blood during ventricular contraction.

Question 9

What is Diastolic pressure?

Answer 9

Arterial blood pressure during ventricular relaxation

Question 10

What is the calculation for Mean Arterial Pressure?

Answer 10

MAP = Diastolic BP + 1/3 Pulse Pressure

Question 11

What is the calculation for pulse pressure?

Answer 11

PP = systolic - diastolic

Question 12

Define MAP

Answer 12

MAP = average pressure in arteries during one cardiac cycle

Question 13

Describe haemodynamic factors affecting blood pressure

Answer 13

Cardiac Output

Total peripheral resistance:
Blood vessel diameter (smaller the lumen, the greater the resistance)
Blood vessel length (longer the vessel, the greater the resistance)
blood viscosity
Compliance (stretchiness) of blood vessel
Pressure gradient

Question 14

Describe the neurohormonal factors that affect blood flow?

Answer 14

Autonomic nervous system:
When sympathetic activity is increased, this increases release of noradrenaline. This induces vasoconstriction of blood vessels and increases HR and BP. Parasympathetic activity is inhibited.

Hormonal control: renin-angiotensin-aldosterone system
E.g. if blood pressure is low:
Beta 2 receptors on Juxtaglomerular cells respond to sympathetic nerve stimulation.
They increase Renin secretion in the kidneys which is involved in the conversion of angiotensinogen (produced by the liver) to angiotensin I.
Angiotensin convening enzyme (ACE) which is found in vascular endothelium converts angiotensin I to angiotensin II.

AII has very important functions:
Increases sympathetic activity

Increases tubular Na and Cl reabsorption and H20 retention to increase blood volume and therefore BP.

Increases aldosterone secretion from the adrenal gland
which stimulates tubular Na and H20 reabsorption.

Increases arteriole vasoconstriction to increase BP.

Increases ADH secretion from the pituitary gland which increases water reabsorption from the collecting duct.

If the blood pressure is HIGH:
Atrial-natriuretic peptides: are released form the right atrium. They induce vasodilation and promote Na and water excretion which lowers blood volume and therefore BP.

Question 15

Define hypertension

Answer 15

Hypertension is a long term medical condition in which arterial blood pressure is persistently elevated

Question 16

describe the stages of hypertension

Answer 16

Normal BP range: 90-119 / 60-79
Prehypertension 120-139 / 80-89
Stage 1: 140-159 / 90-99
Stage 2: >160 / >100

Question 17

Describe the 2 types of hypertension and their causes

Answer 17

Primary (95% of cases):
no direct cause but closely linked with poor lifestyle choices e.g. lack of exercise, alcohol, high salt diet, obesity

Secondary: (5% fo cases)
usually due to an underlying condition e.g. 
endocrine issues (Cushing's disease)
Renal parenchymal disease
Renal artery stenosis 
Drugs e.e.g NSAIDs

Question 18

What are the effects of hypertension on the body?

Answer 18

Increased CO
Increased sympathetic activity, particularly in kidneys
increased renin release, angiotensin II, aldosterone etc.

Question 19

What are the severe consequences of hypertension?

Answer 19

Damages endothelial cells

Increases risk of:
Atherosclerosis 
Stroke
Cerebral haemorrhage
Heart failure 
Myocardial infarction 
Renal failure 
Retinopathy 

Heart disease
 Peripheral artery disease
 Vascular dementia
 Premature death

Question 20

Describe the responses to changes in posture

Answer 20

When someone goes form supine (lying down) to standing position, the effects of gravity cause venous pooling in the vessels below the heart. This increase venous pressure and, to compensate, the veins dilate and the CO, SV and cardiac filling is reduced.

This hypotension is only transient as the baroreceptor reflex detects the change in pressure.

The baroreceptors decrease their firing rate in response to the low blood volume.. This increases sympathetic activity and the HR increases.
Peripheral vasoconstriction increases TPR which helps restore blood pressure.

Question 21

Define and describe postural hypotension

Answer 21

Postural hypotension is a condition where a person’s blood pressure drops abnormally when they stand up form lying down/sitting.

It occurs use to the fair of the baroreceptor reflex and is defined by a decrease in systolic blood pressure of > 15 mmHg

Question 22

What drug can cause postural hypotension?

Answer 22

Alpha adrenoreceptor blocker drugs affect the baroreceptor reflex. They inhibit vasoconstriction which is usually initiated by the baroreceptor reflex upon postural hypotension change.

Question 23

What is rational prescribing?

Answer 23

Principles of Drug selection

Question 24

What are causes of poor drug compliance?

Answer 24

Poor eyesight
Culture and personal beliefs
Large number of tablets
Side effects
Forgetfulness 
Patients Lack information about the disease

Question 25

Consequences of poor drug compliance?

Answer 25

* Reduction in cost effectiveness of medical care * Reduced quality of life * Effect on health and well-being – worsening of condition * Increased risk of morbidity * Excess hospital admissions * More likely to be placed in nursing home

Question 26

What are the risk factors of hypertension?

Answer 26

``` Smoking Obesity Diet (salt) Genetic factors Exercise ``` SODGE

Question 27

List the antihypertensive drugs

Answer 27

``` ACE inhibitor Angiotensin II receptor inhibitor Alpha Adrenoreceptor blocker Beta adrenoreceptor blocker Calcium channel blockers Diuretics ```

Question 28

For Alpha Adrenoreceptor blockers: give 2 examples, mechanism of action and its side effects

Answer 28

e.g. phentolamine (a1 and a2) doxazosin (a1 selective) Effect: • Reduce BP by lowering sympathetic tone in arterioles • Reduce peripheral resistance Side effects: • Postural hypotension (loss of sympathetic vasoconstriction) • Reflex tachycardia (as BP drops, detected by baroreceptors = abnormally fast HR) • Increased closure of internal sphincter of bladder which can cause Benign Prostatic Hyperplasia

Question 29

For Beta Adrenoreceptor blockers: give 2 examples, mechanism of action and its side effects

Answer 29

e.g. propranolol and atenolol Effect: Reduces sympathetic tone in heart and renin release from kidneys This decreases HR, CV and CO ``` Side effects: HIVE Hypoglycaemia Intolerance to exercise Vivid dreams Exacerbates asthma ```

Question 30

Where is ACE usually found?

Answer 30

On vascular endothelium , particular on lungs

Question 31

what are beta and alpha receptor blocker described as?

Answer 31

Competitive reversible antagonists

Question 32

For ACE inhibitors: give 2 examples, mechanism of action and its side effects

Answer 32

e.g. captiprol and enalapril Mechanism: Reduce production of angiotensin II so decreased renal reabsorption so lower blood volume. Decreased aldosterone and ADH secretion, sympathetic tone and arterial vasoconstriction. Side effects: Persistent irritant cough (due to reduced breakdown of bradykinin, a peptide that activates sensory nerves in lung tissue ) Sudden drop in BP after first dose

Question 33

For Angiotensin II receptor blockers: give 2 examples, mechanism of action and its side effects

Answer 33

e.g. losartan and candesartan Blocks At2 receptor so reduces vasoconstriction and decreased blood pressure. Side effects: better than ACE inhibitors as no persistent, irritant cough But they are more expensive so only used if ACE inhibitors don't work

Question 34

What are the differences between the two ATII receptors?

Answer 34

AT1 receptor: mediates vasoconstriction and aldosterone releasing effects AT2 receptor: mediates vasodilation (DON'T WANT TO BLOCK)

Question 35

For diuretics: give AN example, mechanism of action and its side effects

Answer 35

e.g. bendroflumethiazide Decreases blood volume by decreasing renal reabsorption of Na and H2O. Also vasodilator so reduces peripheral resistance. Side effects: Lowers plasma K levels so need to take K supplements

Question 36

For Calcium Channel blockers: give AN example, mechanism of action and its side effects

Answer 36

e.g. diltiazem, verapamil and nifedipine Mechanism: a) Open channel block - cork in the bottle = directly goes into channel and blocks e.g. verapamil and diltiazem work this way b) Allosteric modulation - binds to another site on the calcium channel and reduces channel opening. e.g. nifedipine Effect: blocking calcium entry in vascular smooth muscle: reduces vasoconstriction so = vasodilation Blocking calcium entry in cardiac muscle: reduces contraction, HR and SV so = reduces CO Side effects: Headache Constipation Cardiac dysrhythmias

Question 37

What are the NICE guidelines for prescribing anti-hypertensive drugs?

Answer 37

If person is aged under 55 years: ACE inhibitor or low-cost Angiotensin II receptor blocker If person is aged above 55 OR of African/Caribbean origin of any age: Calcium Channel blocker Next step: Combine Next step: add a thiazide-like diuretic Next step: consider adding another diuretic OR alpha blocker OR beta blocker Seek expert advice

Question 38

Which sex is usually more prone to hypertension and why? | When does this answer change?

Answer 38

Males are more likely to have hypertension as females releases oestrogen which is a vasodilator and keeps blood pressure low. After menopause, oestrogen levels decrease and women become more hypertensive than men.

Question 39

What are the gross structural changes that occur in the vascular wall as a result of hypertension?

Answer 39

* Thickening of tunica media * Increased wall to lumen ratio (media gets thicker and lumen gets smaller which contributes to TPR) * Lengthening of small arteries

Question 40

What is Pulse Wave Velocity?

Answer 40

The velocity at which blood pressure pulse propagates through the circulatory system

Question 41

How does hypertension change the PWV?

Answer 41

Increases the PWV. As arteries reduce their compliance and stiffen, this means that pressure waves are not reduced by their stretch.

Question 42

What's the difference between inward and outward normal remodelling?

Answer 42

Inward has a smaller lumen and outward has a larger lumen

Question 43

What's the difference between hypertrophic and hypotrophic remodelling?

Answer 43

Hypertrophic has more growth in the vessel wall compared to hypotrophic

Question 44

What type of vessel remodelling is likely in patients with hypertension?

Answer 44

Eutrophic/hypertrophic inward remodelling

Question 45

How effective are different hypertensive drugs at restoring vascular structural changes?

Answer 45

Beta Blocker: not effective ACE inhibitor: slightly helps to improve the media-lumen ratio Angiotensin II receptor blocker: slightly helps to improve the media-lumen ratio Renin inhibitor: improves the Media to Lumen Ratio

Question 46

How does hypertension affect the fenestrae in endothelium ?

Answer 46

The inner surface of the internal elastic lamina has fenestrae which are small holes that are the only way endothelial cells can communicate with the smooth muscle that lies in tunica media. Endothelial cells allow flow mediated vasodilation. The action of blood against the endothelial cells triggers the formation of Nitric Oxide which is an important vasodilator. it goes through the fenestrae and relaxes the smooth muscle. Hypertension causes changes in the diameter and number of small holes. This reduces the contact point so smooth muscle doesn't relax as much and there is less vasodilation.

Question 47

What hypertensive therapy can normalise flow mediated vasodilation?

Answer 47

ACE inhibitors

Question 48

What is the effect of angiotensin II on vascular structure?

Answer 48

In hypertension, there is more AGT II in blood plasma so more vasoconstriction. AGT II also has mitogenic effects which stimulates smooth muscle growth and MMPs. This causes vascular structural changes.

Question 49

What increases formation of tissue fluid (oedema) ?

Answer 49

Increased permeability of capillary wall | Dilatation on arterioles with a constant Mean Arterial Pressure.

Question 50

Where is ADH synthesised and released from?

Answer 50

Synthesised in Hypothalamus and released from posterior pituitary gland

Question 51

What is the relationship of "resistance to flow" to vessel length, viscosity and radius?

Answer 51

Directly proportional to viscosity and blood vessel length. Indirectly proportional to radius

Question 52

What effects does high blood pressure have on Potassium levels?

Answer 52

Decrease in potassium (hypokalaemia)

Question 53

What effect does vasodilation have on capillary pressure and interstitial fluid?

Answer 53

Vasodilation increases capillary pressure and interstitial fluid formation.