Lecture 4: Pathophysiology of CVD and Heart Failure Flashcards
What is the protective role of the healthy endothelium against plaque formation in arteries?
A healthy endothelium releases nitric oxide which in turn will:
Vasodilate blood vessels
Reduce platelet and monocytes stickiness
Reduced multiplication of smooth muscle cells of artery walls
Reduces superoxide radicals
Damaged endothelium will impair the release of NO - glycocalyx
Define MCSF and outline its role in the development of atherosclerosis plaque?
Macrophage colony stimulating factor is a cytokine which influences cells to form into macrophages. MCSF differentiates monocytes within the sub endothelium space to then engulf the oxLDL which in turn results in the formation of foam cells.
What is the role of TNF-a and VCAM1?
Tumour Necrosis factor A TNF-a is an inflammatory cytokine with both pro+anti inflammatory functions. When released, TNF-a activates NF-kb and amplifies the inflammatory response. TNF-a also stimulates the acute phase response on the liver.
Vascular Cell adhesive molecule1 VCAM1 binds to the integrin on the monocytes in order for them to stick to the endothelium where they will later proceed to transmigrate.
What is a key player in the breakdown of the fibrous cap and subsequently result in the release of the thrombus?
Continued inflammatory response increases the atheroma within the sub endothelium space. This continuous increase also results in an increase of Y-interferon, this cytokine prevents the formation of new collagen and deteriorates existing collagen enzymes. This results in a rupture of the atheroma as a result of collagen weakness, the thrombus is then released in the blood stream where it could result in Myocardial infarction, stroke, deep vein thrombosis - depending on where the thrombus stops.
How does the cantos study (ridker, 2017) support the ‘inflammatory hypothesis’ of heart disease?
The CANTOS study focused solely on inhibiting the inflammation process, specifically Interleukin 1 which In turn will negate the effects of IL-6 and therefore reduce C reactive Protein. CRP is a marker for measuring levels of inflammation. The CANTOS study replicated the same 15% reduction in myocardial infarction and CVD risk when compared with previous aggressive lipid lowering trails.
What does ventilation-perfusion mismatching represent in patients with HF - include the physiological mechanism and the key symptom?
The physiological mechanism is the hearts inability provide enough blood to the lungs for adequate perfusion a result this increases CO2 levels within the blood which stimulates chemoreceptors in the brain to increase the rate and depth of breathing in attempt to restore blood pH. A common symptom is dyspoea or shortness of breath.
Dead space
Dyspnoea is a common symptom of heart failure. Briefly explain the physiological mechanism for this?
As demand increases the heart is less likely to meet the demands and supply oxygenated blood around the body. Therefore the lungs can’t diffuse O2 to the blood or expel the CO2. This results in an increase of CO2 which stimulate a signal to the chemoreceptors of the brain and the autonomic nervous system which in turn results in an increase of rate and depth of breath.
What is the main cause, key characteristic and symptoms of systolic heart failure?
The causes of HFrEF: uncontrolled hypertension, Myocardial Infarction, Valve disease and Idiopathic dilated cardiomyopathy (impaired contractility).
The key characteristics of HFrEF is an elevated afterload (stress on Lventricle wall during ejection) as well as a higher than normal EndDiastolicValue and reduced EjectionFraction.
The key presenting symptoms shortness of breath, fatigue, swollen ankles, pulmonary oedema, weight gain - fluid retention.
How does smooth muscle get in to the sub endothelium space?
When macrophages engulf oxLDL in the sub endothelium space they become foam cells. Endothelium foam cells release growth factors FGF and PDGF, when these growth factors are released which results in the proliferation and migration of smooth muscle cells to the sub endothelial space.
What is the main cause, key characteristic and symptoms of diastolic heart failure?
It is caused as a result of left ventricular hypertrophy, myocardial ischaemia,
HDpEF attributes to 30-50% of all cases. This condition is caused as a result of a reduced EDV due to inappropriate relaxation of the ventricle. Another reason could be reduced compliance/increased stiffness OR both symptoms present at once.
