Pathopsyiology of ischaaemic heart disease

Question 1

What causes the lub dub sound when the heart contracts

Answer 1

S1 = ventricular valve closing
S2 = aortic valve closing (semilunar valve)

Question 2

What % of total cardiac output does the myocardium get

Answer 2

Roughly 5% and increased myocardium demand can cause that to rise by 3-4x

Question 3

What caused blood to flow around the body

Answer 3

The left ventricle contracts creating a high pressure inside the LV, the pressure inside is higher than in the lumen and so blood flows from the LV to lumen of the aorta.

Question 4

what is the equation for 02 demand

Answer 4

Blood flow x ateriovenous 0xygen concentration difference.
Volume of blood x by the difference in the concentration of oxygen in the arteries and the veins.

Question 5

What is the equation for coronary blood flow

Answer 5

Aortic pressure/ coronary resistance

Question 6

What is hypoxia

Answer 6

When the o2 levels are too low for tissues to maintain homeostasis

Question 7

Is oxygen a vasoconstrictor or dilator

Answer 7

Oxygen is a vasoconstrictor

Question 8

What happens when oxygen concentrations are low

Answer 8

• stops AMP regenerating to ATP
  Causes veins to dilate because:
• adenosine levels rise in myocardium and then bind to the R2 adenosine receptor on vascular muscle directly causing vasodilation
• the accumulation of lactate, H+ ions and prostacyclin

Question 9

What is prostacyclin

Answer 9

It’s a member of the prostaglandin family (bioactive lipids), it is released by the endothelial cells and causes vasodilation and prevents platelet aggregation (clustering)

Question 10

What are compounds cause vasodilation and how

Answer 10

Bradykinin (a protein that causes inflammation), ach and histamine by releasing a nitric oxide which diffuses into the vascular muscle and raises cGMP activating protein kinase G.

Question 11

What is arthritis

Answer 11

When the veins become inflamed

Question 12

What is artherosclerosis

Answer 12

When the veins become hardened due to a build up of plaque in the veins

Question 13

Embolism

Answer 13

When blood moves slowly in the veins, a blood clot can form and a bit of the clot can break off and move in the blood stream.

Question 14

What is endocarditis

Answer 14

When the endocardium (thin layer smooth tissue that lines the chambers of the heart) becomes inflamed

Question 15

What are modifiable risk factors to related to ischaemic heart disease

Answer 15

• Hypertension
• hypercholesterolaemia
• smoking
• diet
• sedentary lifestyle
• obesity

Question 16

What is angina pectoris

Answer 16

Chest pain caused by Angina, this occurs when the heart muscles switch to anaerobic metabolism because of low oxygen supply

Question 17

What issue does angina present

Answer 17

Transient chest pain during moderate exercise and so the person stops exercising and becomes more unfit then chest pain starts during mild activity and so the person stops that and then becomes even more unfit until eventually chest pain starts during day to day activities

Question 18

Consequences of myocardial ATP deficiency

Answer 18

• Impairment of ventricular systole
  Lack of oxygen to the myocardium means that contractility is reduced so the load (how hard it contracts) increases and so the end systolic volume (vol. of blood in the ventricles after systole) goes up however the stroke volume falls so the
• decreased myocardial relaxation
  Hypertrophy of the cardiac muscle is reduced and so diastolic filling is reduced. Furthermore, the effect of ATP on the actin-myosin separation is reduced.
• pulmonary congestion
  Back flow and cardiac failure and blood flowing from the LV back into the LA - systolic mitral regurgitation

Question 19

What are the three types of angina

Answer 19

• stable angina,
  Only occurs with exertion or stress and is relieved by stress, is an indication of coronary narrowing
• unstable angina, occurs with minor exertion and due to incomplete occlusion (no fully blocked vessel), can experience pain at rest and the blood flow is enough so that the heart muscle doesn’t die or have a heart attack
• variant angina,
  Complete coronary vasospam, pain at rest is due to the lack of o2

Question 20

What is atrial fibrillation

Answer 20

A condition that results in irregular and fast heart beats

Question 21

Consequences of myocardial ischemia

Answer 21

The lack of o2 to myocardium results in the anaerobic production of ATP and thus a build up of and lactate acid which dissociates into H+ and lactate. Combination of low ATP and H+ ions cause abnormal ventricular contraction

Question 22

What is a myocardial infarction

Answer 22

A heart attack,
Extended myocardial ischemia causes myocardial necrosis which results in ventricular remodelling (the ventricles of the heart change in size, shape and function)
In the majority of cases, coronary stenosis and acute thrombus cause myocardial infractions with necrosis occurring 20-30 minutes after occlusion

Question 23

What enzymes are released into he blood from necrotic cardiomyocytes

Answer 23

• Myocardial creatine kinase (CK-MB)
• cardiac troponin T
• cardiac troponin I
• cardiac lactate dehydrogenase

Question 24

What are the treatment options for angina

Answer 24

1) risk factor reduction
2) evidence based therapies for stable angina
3) therapies for refractory angina
4) experimental and palliative options

Question 25

How does nitric oxide cause smooth muscle relaxation

Answer 25

• ACh binds to G protein and causes the IP3 (Inositol trisphosphate, causes ca2+ to released from stores) to be produced
• IP3 causes ca2+ to be released from endoplasmic reticulum
• Ca2+ and calmodulin (a protein) from a complex and bind stimulating NO synthesis
• NO diffuses from the endothelial cells into the adjacent smooth uncle cells
• NO activates guanylyl cyclase to make cGMP
• cGMP activates protein kinases G
• kinase G activates myosin light chain phosphatase
• myosin light chain dphophatase dephosphorylates the myosin light chain leading to smooth muscle relaxation

Question 26

What nitrate drugs are used, what are the used to treat and what are their side effects

Answer 26

Nitrate drugs: isosorbide nitrate, glyceryl nitrate
Used to treat: stable angina, variant angina, acute coronary symptoms.
Side effects: tachycardia, headaches and postural hypertension

Question 27

Why is Nicorandil used to treat angina

Answer 27

A drug that has a dual mechanism of action:
- NO donor, which causes the relaxation of veins, systemic and pericardial arteries, maximises the coronary blood flow.
- opens ATP dependant potassium channels, this leads the hyperpolarisation leading to artery dilation.
Cardiac repolarisation results in reduced cardiac work.

Question 28

What are three examples of beta blockers

Answer 28

• ## Propanalol, carvedilol, atenelol

Question 29

How do b blockers work

Answer 29

Block cardiac b1 adrenoreceptor and reduced generation of intracellular cAMP thus decreases the heart rate (inhibits hyperpolsrisation at the SA node) thus reducing the force of the contraction and lower blood pressure

Question 30

What type of angina are b blockers used for

Answer 30

Stable angina and variant angina

Question 31

3 side effects of b blockers

Answer 31

Cardioselectivity (the receptors become less/more receptive to certain neurotransmitters), bronchospasms (muscles lining of airways become restricted) and hypoglycemia (low glucose)

Question 32

What are ca2+ channel blockers used to treat

Answer 32

Stable angina and variant angina

Question 33

How do ca2+ channel blockers work

Answer 33

Peripheral (parts of the body further out) vasodilation (causes vascular system to dilate) these are drug that dilate the distal vascular system.
Also reduced cardiac workload.