How the cardiovascular system fails

Question 1

Name the functions/activities of the endothelium.

Answer 1

Local control of perfusion

Vasodilatation

Fluid filtration

Haemostasis

White cell recruitment

Angiogenesis

Hormone trafficking (including transcytosis)

Question 2

Name two types of stroke (based on their cause).

Answer 2

Ischaemic

Haemorrhagic

Question 3

Name three processes that might damage a blood vessel (rather than damaging the tissue around it).

Answer 3

Intravascular Trauma such as PCI

Atherosclerosis

Diabetes

Question 4

Which vessel has the highest compliance: an artery (eg radial artery), a vein (eg radial vein) or a capillary?

Answer 4

The vein. It is stretchiest.

Question 5

Name four factors that would increase the likelihood that the flow in a vessel is turbulent.

Answer 5

High flow rate

Low viscosity

Branching (junctions)

Mixing with flow from other vessels

Obstacles

Wide radius

Question 6

What is aldosterone and why is it relevant to cardiovascular function?

Answer 6

Aldosterone is hormone produced by the adrenal cortex that acts on the kidney to cause it to reabsorb more Na+ (and thus more water), thus increasing plasma volume and resulting in higher blood pressure.

Aldosterone is a steroid hormone in the class of mineralocorticoids.

Aldosterone acts at the collecting ducts of the nephron.

Aldosterone receptors are blocked by the drug spironolactone, which is used under some circumstances to treat hypertension

Question 7

What is renin and why is it relevant to cardiovascular function?

Answer 7

renin is an enzyme (and a hormone) released from the kidney.

renin is one of the initiators in the Renin-angiotensin-aldosterone system. RAAS activation leads to arterial vasoconstriction and increased fluid retention

Renin catalyses the conversion of angiotensinogen into angiotensin I. Note that the active molecule is angiotensin II, which requires angiotensin converting enzyme

renin is a polypeptide

renin acts to increase blood pressure, and drug antagonists of renin can be used as antihypertensives.

Question 8

What is ADH and why is it relevant to cardiovascular function?

Answer 8

ADH (antidiuretic hormone) is a hormone manufactured by the hypothalamus and then released from the posterior pituitary.

ADH is also called vasopressin

It acts on the kidney to cause it to reabsorb more water, thus increasing plasma volume and resulting in higher blood pressure.

ADH is a peptide hormone

ADH acts at the collecting ducts of the nephron.

It induces that addition of water channels (aquaporins)

Question 9

What is afterload?

Answer 9

Afterload is the sum of all forces opposing ventricular ejection, or the pressure that the chambers of the heart must generate in order to eject blood out of the heart and thus is a consequence of the aortic pressure (for the left ventricle) and pulmonic pressure or pulmonary artery pressure dedicated (for the right ventricle). The term has no specific measurement associated with it, but end systolic pressure is suggestive of the concept. Afterload can be increased by increasing aortic (LV) or pulmonary artery (RV) pressure, or by valve stenosis that creates an obstacle to ejection.

Question 10

Give an example in heart failure of a compensation mechanism.

Answer 10

Increased sympathetic drive and increased fluid conservation to increase contractility and blood volume, respectively.

Question 11

Name two different kinds of ventricular hypertrophy and explain the difference between them.

Answer 11

Concentric hypertrophy thickens the ventricular wall, whereas eccentric hypertrophy results in dilatation.

Question 12

What is cardiac remodeling, and (at the organ level) what causes it to occur?

Answer 12

Remodeling is growth of Cardiac Muscle, which results in a change is size, shape or function of the cardiac chamber(s). It typically takes the form of hypertrophy or dilatation, and it can be compensatory or pathological. The cause of remodeling is typically a response to increases in afterload or preload, so it can result from MI, hypertension or valve disease.

Question 13

Name two drugs or drug classes that reduce cardiac remodelling in heart failure.

Answer 13

• ACE inhibitors, including enalapril or captopril, and
• aldosterone receptor inhibitors (also known as K+ sparing diuretics), including spironolactone.
• 3rd generation beta blockers (e.g. carvedilol) may also do so.

Question 14

Would decreased ventricular compliance lead to decreased, increased or the same level of preload?

Answer 14

Decreased ventricular compliance would lead to decreased preload, because the ventricle would not expand. Examples of decreased compliance would include increased fibrosis.

Question 15

If arterial compliance was increased, what effect would that have on pulse pressure: increase, decrease or neither?

Answer 15

Increased arterial compliance would result in a decreased pulse pressure. During systole arteries (including the aorta) would stretch (and absorb energy) leading to decreased pressure downstream from the stretching. Then during diastole, the stretched arteries would constrict (because they are under less upstream pressure), and as the arteries constrict there would be increased diastolic pressure downstream.

Question 16

Would decreased venous compliance lead to increased, decreased or the same level of preload in the right ventricle?

Answer 16

Increased preload, because the venous system would store less fluid.

Question 17

Name three of the main symptoms and signs of heart failure.

Answer 17

Fatigue, especially during exertion.

Peripheral oedema.

Dyspnoea (including orthopnoea, etc).

Question 18

What is the main difference between left heart failure and right heart failure in terms of their symptoms?

Answer 18

Left heart failure would lead to respiratory symptoms, because of the back-up in the pulmonary circulation, whereas right heart failure would lead to systemic symptoms due to back-up preventing proper venous return.

Left HF symptoms include dyspnoea, orthopnoea, and paroxysmal nocturnal dyspnoea.

Right HF symptoms include peripheral oedema and ascites

Question 19

Name the symptoms of pulmonary oedema.

Answer 19

Dyspnoea/orthopnoea

Pale skin

Excessive sweating

Ultimately hypoxia

Question 20

What are the main treatments for heart failure?

Answer 20

ACE inhibitors, loop diuretics, beta blockers, angiotensin receptor blockers. Sometimes digoxin is given, but it has not been shown to improve outcomes, but only immediate symptoms. K+ sparing diuretics (aldosterone receptor antagonists) may also be given under some circumstances

Question 21

Name two different types of shock (based on its cause).

Answer 21

• Hypovolaemic shock – e.g. caused by haemorrhage
• Cardiogenic shock

•

•Also Distributive shock (where blood vessels dilate)

–Includes septic shock and anaphylactic shock

Question 22

What hormone from the pituitary has a direct effect on fluid retention and indirect effect on arterial pressure?

Answer 22

Vasopressin, also known as ADH

Question 23

What does angiotensin II do?

Answer 23

It’s a strong vasoconstrictor.

Increases fluid retention by increasing Na+ reabsorption at the proximal convoluted tubule of the nephron.

Contributes to ventricular hypertrophy and remodelling.

Stimulates aldosterone secretion from adrenal glands

Question 24

What is myocardial infarction?

Answer 24

A region of heart tissue that is dying or dead, usually caused by a blocked coronary artery.

Question 25

What are the biggest contributors to the progression of atherosclerosis?

Answer 25

Immune activity

Hyperlipidaemia

Can also say:

Smoking, obesity, diet, sedentary lifestyle, genetic predisposition

Question 26

__________ is the disease process most likely to cause angina pectoris.

Answer 26

CAD, IHD, CHD, etc

You could also say atherogenesis

Question 27

Name 4 classes of diuretic drugs.

Answer 27

Thiazide diuretics

Loop diuretics

Thiazide-like diuretics

K+ sparing diuretics (aldosterone receptor antagonists)

Question 28

What is the role of plaque rupture in MI?

Answer 28

Plaque rupture is usually the immediate cause of myocardial infarct; it leads to a thrombus that can completely occlude a vessel that was previously only partially occluded.

Question 29

What causes the increased rate and contractility of the heart during MI?

Answer 29

Sympathetic activity.

It also causes increased peripheral resistance and increased risk of arrhythmia. It is a partially compensatory mechanism, but it has high risks associated with it.

Question 30

What are the main symptoms of myocardial infarct?

Answer 30

•Death of one region in the heart

–

•Sudden, crushing chest pain *E

Question 31

What are the main symptoms of heart failure?

Answer 31

•Heart pumps out insufficient blood

•

•Fatigue, dyspnoeia, oedema

Question 32

What are the main drugs for heart failure?

Answer 32

•ACE inhibitors

Decrease fluid

Decrease peripheral resistance

•Beta blockers

Decrease peripheral resistance

Decrease heart rate & force of contraction

• Angiotensin II receptor antagonists
• diuretics

Question 33

Explain the roles of osmotic pressure and hydrostatic pressure in net fluid motion over the length of a capillary.

Answer 33

There are two forces determining the tendency to move fluid across the wall of a capillary: net hydrostatic pressure and net osmotic pressure. Barring traumatic pathologies, Net hydrostatic and osmotic pressure are relatively constant in the extracellular space. When blood enters the capillary, its hydrostatic pressure is higher than in the ECF. The net fluid flow is outward, but blood proteins cannot leave. As a result, downstream inside the capillary there is increased osmotic pressure (tending to pull fluid into the capillary). In addition, because there is resistance along the length of the tiny capillary, downstream the hydrostatic pressure pushing fluid outward is reduced. The net result is that fluid tends to be pulled into the capillary. This fluid replaces the fluid lost at the beginning of the capillary. The net fluid transfer between these points is mostly conducted by the lymphatic system.

Question 34

In atherosclerosis systolic BP increases while diastolic BP decreases. Why?

Answer 34

Pulse pressure increases due to decreased compliance. This means that reduced (or no) kinetic energy is stored during systole or released during diastole, so blood pressure much more closely follows ventricular pressure.

Question 35

What is the effect of wall tension on a blood vessel?

Answer 35

Wall tension would tend to stretch out the wall or rip it (causing it to burst)

Question 36

Explain how “left-sided” heart failure causes its stereotypical symptoms.

Answer 36

Left sided heart failure means that there is not enough cardiac output to properly perfuse the systemic circulation, which will lead to fatigue during exertion, but left sided heart failure is known for its respiratory symptoms that are caused by the fact that blood attempting to leave the pulmonary circulation cannot because of back pressure due to the left heart not emptying enough. Right heart pumps into lungs but left heart does not clear it fast enough which leads to an increase in hydrostatic pressure in pulmonary circulation. Fluid leaks out of blood vessels and into lungs, which leads to the symptoms of “Congestive Heart Failure”: orthopnea, dyspnoea, and paroxysmal nocturnal dyspnoea

Question 37

With regard to heart failure: list the most common causes, diagnostic criteria, and therapies.

Answer 37

• Causes: Ischaemic heart disease and hypertension
• Diagnostic criteria: LVEF < 45% (echocardiography), NYHA class (dyspnoea vs exertion)
• Therapies: Diuretics, ACE inhibitors, Ang antagonists, Digoxin (this last one is now controversial)

Question 38

Which vessel is subject to greater wall tension (and what is the result to the structure of the vessel): the aorta or a capillary?

Answer 38

The aorta has a much bigger radius (as well as a much higher pressure), so its wall has to withstand much more tension. Thus the walls of the aorta are much thicker than the walls of the capillary

Question 39

List 3 reasons why the abdominal aorta is a common site for aneurysms.

Answer 39

It is a branching point, leading to eddies and turbulence, which is why aneurysms typically occur there.

Because it is a large vessel, it has very high wall tension and also high levels of turbulence

Because it is in the aorta, it has high pressure, which also increases wall tension

Question 40

Why do capillary beds not result in massive resistance?

Answer 40

Because there are so many of them in parallel. Even though the capillaries are very small, the sheer number of them means that the cross sectional area for all the capillary beds in the body is quite large.

Question 41

In this graph, does curve B have a higher or lower compliance?

Answer 41

B has a lower compliance than A. Compliance is directly related to the slope of the line for a pressure vs volume graph

Question 42

If a patient was suffering from chronic low output heart failure, would they be in a low output state or a low volume state?

Answer 42

Heart failure is a low output state because the cardiac output is low

Question 43

If a patient was in a low volume state, would it be better to give the patient a fluid challenge or diuretics?

Answer 43

A low volume state might be partially corrected by intravenous fluid, while diuretics would make the situation worse

Question 44

Briefly explain the differences between ventricular pressure overload, ventricular volume overload and fluid overload?

Answer 44

Ventricular pressure overload is caused by high afterload – high resistance to myocyte contraction – during systole (eg aortic valve stenosis) and results in concentric hypertrophy

Ventricular volume overload is caused by high preload – overstretching of cardiomyocytes during diastole (eg high central venous pressure) and results in eccentric hypertrophy (dilated hypertrophy).

Fluid overload is another term for hypervolaemia and results in high central venous pressure as well as dyspnoea, oedema and pulmonary congestion (ie similar symptoms to heart failure). Fluid overload typically results in ventricular volume overload.

Question 45

Briefly explain the differences in the effects of ADH and aldosterone on the kidney?

Answer 45

• ADH is directly responsible for reducing diuresis. It allows for increase water resorption (due to increased water channels) at the level of the collecting ducts and the distal convoluted tubules.
• Aldosterone reduces natriuresis (sodium loss to urine), and thus indirectly reduces diuresis.

Question 46

Why is decompensated heart failure a positive feedback loop?

Answer 46

• When low output heart failure is no longer able to compensate, the heart itself is significantly affected.
• The heart tissue has very high oxygen demands. If these demands are not met, the heart weakens, resulting in lower contractility.
• If contractility is lower, this will also lower the oxygenated blood supply to the heart tissue

–If pressure generation is poor, this will have a serious effect on flow through the coronary arteries, which only allow flow during diastole, when aortic pressure is at its lowest

•This is a positive feedback loop that results in cardiogenic shock, which is often fatal, even with the best medical care.