Pathophysiology of CVD and CHF Flashcards Preview

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Flashcards in Pathophysiology of CVD and CHF Deck (13)
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1
Q

What is upstream inflammatory response and roles

A

WBC (monocytes & lymphocytes)

2nd line of defence in response to injury/damage/illness

2
Q

What is downstream inflammatory response TNF-a and roles

A

Multiple roles and effects (pro&anti)

In relation to atherosclerosis, it is produced by activated T-cells

Activates NF-kB

Stimulates acute phase response on the liver

3
Q

What is downstream inflammatory response IL-6 and roles

A

Multiple roles and effects like TNF-a

Regulates immune function (pro&anti)

In relation to atherosclerosis, released from smooth muscle cells in response to macrophage derived TNF-a

Messenger cytokine

4
Q

What is CRP (C reactive protein) and roles

A

Acute phase protein synthesised by hepatocytes (liver)

Released in response to IL-6

High sensitivity CRP

Stable biomarker

5
Q

Look at Jupiter study, Ridker, 2003!!

A

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6
Q

What were the HRs across all Cv endpoints 150mg

A

Primary - 0.85

Secondary - 0.83

Myocardial infarction - 0.76

Urgent revascularization - 0.64

Any coronary revascularization - 0.68

Stroke - 0.98

cardiac arrest - 0.63

CV death - 0.90

All cause morality - 0.92

7
Q

What were the HRs at 300mg

A

Primary - 0.86

Secondary - 0.83

Myocardial infarction - 0.84

Urgent revascularization - 0.58

Any coronary revascularization - 0.70

Stroke - 0.80

Cardiac arrest - 0.46

CV death - 0.94

All cause morality - 0.94

8
Q

What is the protective role of the healthy endothelium against plaque formation in arteries?

A

A variety of factors lead to
atherogenesis:
 Reduction in bio-availability of NO

 Increased oxidative stress
- e.g. oxidised LDL

 Vasoconstriction by endothelin-1
(ET1)

 Endothelium upregulates ET1 in
response to oxidised LDL etc.

9
Q

Define M-CSF and outline its role in the development of atherosclerotic plaque

A
  1. Macrophages engulf oxLDL  foam cells
  2. Foam cells multiply  fatty streak/atheroma
  3. Secretion of inflammatory cytokines and
    growth factors
  4. Smooth muscle cell proliferation
  5. Collagen  plaque holding foam cells in
    • Macrophage Colony-Stimulating Factor (M-CSF)
10
Q

What is the role of TNFa and VCAM-1

A
  1. *Change to endothelial function
  2. *Infiltration of oxidised LDL into intimal
    layer
  3. ^Adhesion molecules are expressed on
    endothelium to attract WBC’s
  4. # WBC migrate into intima  macrophages• *Nuclear Factor Kappa Beta (NF-κβ)
    • ^Vascular Cell Adhesion Molecule 1 (VCAM-1)

    # Monocyte Chemoattractant Protein 1 (MCP-1)
11
Q

What is a key player in the breakdown of
the fibrous cap and subsequent
thrombus release? Describe.

A
  1. Continued inflammation increases enzymes
    that interfere with stability and strength of
    collagen matrix
     prevent new collagen*
     destructs existing collagen (enzymes)
  2. Weakens plaque  rupture of atheroma
  3. Thrombus released into blood and is most
    probable cause of MI
    * γ-Interferon
12
Q

How does CANTOS study (Ridker, 2017) support inflammatory hypothesis’ of heart disease

A

Look at Ridker 2017

13
Q

What does ventilation-perfusion mismatching represent in patients with heart failure - include the physiological
mechanism and the key symptom?

A

↑ CO2 & H+  Chemoreceptors (metabolic acidosis)

 ↑ Rate & depth of respiration in attempt o restore pH

Peripheral muscle receptors (metabo- or mechanoreceptors) produce an abnormal ergoreflex, resulting in an abnormal VE/VCO2 slope during exercise.