Pathophysiology Of CVD And HF Flashcards
What is the protective role of the healthy endothelium against plaque formation in arteries?
Reduces platelet stickiness Dilates blood vessels Reduces monocyte stickiness Reduces multiplication of smooth muscle cells of artery wall Reduces release of superoxide radicals Reduces oxidation of LDL cholesterol
Define M-CSF and outline its role in the development of atherosclerotic plaque.
Macrophage colony-stimulating factor
It causes the macrophages to engulf oxLDL creating foam cells
The foam cells multiply causing a fatty streak
Inflammatory cytokines and growth factors are secreted
Smooth muscle cell proliferate
The collagen causes the plaque to hold the foam cells in
What is the role of TNFa and VCAM-1?
TNFa (tumor necrosis factor - alpha) - produces by activated T cells stimulates the inflammatory response and activates NF-KB
VCAM-1 (vascular cell adhesion molecule - 1) - the molecules are expressed on the endothelium to attract w.b.c.
What is a key player in the breakdown of the fibrous cap and subsequent thrombus release? Describe.
The continued inflammation increases enzymes that interfere with the stability and strength of the collagen matrix
Y-interferon - prevents new collagen and destructs existing collagen
Which weakens the plaque causing a rupture of atheroma
Thrombus is released in to the blood
How does the CANTOS STUDY (RIDKER, 2017) support the ‘inflammatory hypothesis’ of heart disease?
Low LDL but high CRP - given statin reduced events due to reducing inflammation
Reducing inflammation without lowering cholesterol - lower incidence
Gave medicine that targets IL-1b
Lowers IL-1, IL-6 which reduces CRP by about 40%
What does ventilation-perfusion mismatching represent in patients with heart failure - include the physiological mechanism and the key symptoms?
Increase in CO2 and H+ detected by chemoreceptors
Therefore the rate and depth of respiration is increased to restore pH
Inadequate perfusion of the tissues with oxygen leads to mismatching and dyspnoea/breathlessness
(ventilate the top of lungs but circulate from the bottom of the lungs)
Factors that lead to atherogenesis
Reduction in bio-availability of NO
Increase oxidative stress
Vasoconstriction by endothelium-1
Endothelium up regulates ET1 in response to oxidised LDL
A decrease in NO leads to
Decrease dilates blood vessels
Increase: platelet stickiness , monocytes stickiness , multiplication of smooth muscle cells of artery wall , release of superoxide radicals , oxidation of LDL cholesterol
What is the role of IL-6?
It is released from smooth muscle cells in response to macrophage derived TNFa - messenger cytokine
What is the role of CRP?
Used as a measure of inflammation (other 3 are pro and anti so can’t be measured)
Synthesised by hepatocytes (liver)
Released in response to IL-6
High sensitivity CRP (early stage-low grade inflammation)
Stable biomarker
Explain the pathophysiology caused by NF-KB
NF-KB causes a change to the endothelial function
Causing the infiltration of oxidised LDL into the intimal layer
VCAM-1 is expressed on the endothelium to attract w.b.c
MCP-1 causes w.b.c to migrate into the intima and become macrophages
What is Heart failure and name some symptoms?
Inability of the heart to provide sufficient cardiac output to meet the body’s metabolic needs.
Shortness of breath, fatigue, swollen ankles, pulmonary oedema, weight gain
Describe systolic heart failure and name causes
Can’t produce the force to push the blood
Impaired ventricular contractility
elevated afterload
higher EDV and reduced EF
Causes; uncontrolled systemic hypertension, MI, valve disease
Describe diastolic heart failure and name causes
Heart fibrotic not elastic
reduced EDV cause by inappropriate relaxation of the ventricle, reduced compliance
Causes; LVH, myocardial ischaemia
Describe reduced Q
Decrease preload (decrease SV) and increased afterload (increase resistance) Decreased perfusion Decreased SNS activity RAAS stimulation Increased inflammation
