Pathopsyiology of ischaaemic heart disease Flashcards
What causes the lub dub sound when the heart contracts
S1 = ventricular valve closing
S2 = aortic valve closing (semilunar valve)
What % of total cardiac output does the myocardium get
Roughly 5% and increased myocardium demand can cause that to rise by 3-4x
What caused blood to flow around the body
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.
what is the equation for 02 demand
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.
What is the equation for coronary blood flow
Aortic pressure/ coronary resistance
What is hypoxia
When the o2 levels are too low for tissues to maintain homeostasis
Is oxygen a vasoconstrictor or dilator
Oxygen is a vasoconstrictor
What happens when oxygen concentrations are low
- 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
What is prostacyclin
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)
What are compounds cause vasodilation and how
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.
What is arthritis
When the veins become inflamed
What is artherosclerosis
When the veins become hardened due to a build up of plaque in the veins
Embolism
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.
What is endocarditis
When the endocardium (thin layer smooth tissue that lines the chambers of the heart) becomes inflamed
What are modifiable risk factors to related to ischaemic heart disease
- Hypertension
- hypercholesterolaemia
- smoking
- diet
- sedentary lifestyle
- obesity
What is angina pectoris
Chest pain caused by Angina, this occurs when the heart muscles switch to anaerobic metabolism because of low oxygen supply
What issue does angina present
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
Consequences of myocardial ATP deficiency
- 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
What are the three types of angina
- 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
What is atrial fibrillation
A condition that results in irregular and fast heart beats
Consequences of myocardial ischemia
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
What is a myocardial infarction
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
What enzymes are released into he blood from necrotic cardiomyocytes
- Myocardial creatine kinase (CK-MB)
- cardiac troponin T
- cardiac troponin I
- cardiac lactate dehydrogenase
What are the treatment options for angina
1) risk factor reduction
2) evidence based therapies for stable angina
3) therapies for refractory angina
4) experimental and palliative options
How does nitric oxide cause smooth muscle relaxation
- 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
What nitrate drugs are used, what are the used to treat and what are their side effects
Nitrate drugs: isosorbide nitrate, glyceryl nitrate
Used to treat: stable angina, variant angina, acute coronary symptoms.
Side effects: tachycardia, headaches and postural hypertension
Why is Nicorandil used to treat angina
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.
What are three examples of beta blockers
- ## Propanalol, carvedilol, atenelol
How do b blockers work
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
What type of angina are b blockers used for
Stable angina and variant angina
3 side effects of b blockers
Cardioselectivity (the receptors become less/more receptive to certain neurotransmitters), bronchospasms (muscles lining of airways become restricted) and hypoglycemia (low glucose)
What are ca2+ channel blockers used to treat
Stable angina and variant angina
How do ca2+ channel blockers work
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.
