Cardiovascular Physio Logic Process

8/11/2019 Cardiovascular Physio Logic Process

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Pathophysiology of

Cardiovascular Disease

Cardiovascular Physiology and

Pharmacology


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Heart Disease

There is no such thing as heart disease

There is cardiovascular disease


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Cardiovascular System

Heart

Blood Vessels

Arteries

Arterioles

Capillaries

Veins

Venules

Blood components platelets, leucocytes, fibrinogen, PAI-

1,vitamins


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Neurohormonal Components

Sympathetic System

Renin-Angiotensin-Aldosterone System Endothelin

Natriuretic peptides

Nitric oxide


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a s e purpose o ecardiovascular system?

Supply oxygen and nutrients to the

tissues and organs, and to remove

waste products

To defend the supply of nutrients to

organs by

maintaining cardiac output

sympathetic, RAAS, endothelin, nitric oxide,

fluid retention

maintaining organ perfusion pressure


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The Heart

The heart is a muscle which must operate

in all conditions

Operates 24 hours a day

Possesses own blood supply

The right heart pumps deoxygenated

blood to the lungs The left heart pumps oxygenated blood to

the rest of the body


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Anatomy

Four chambers

Right Heart (Low Pressure)

Right Atrium, Right Ventricle

Left Heart (High Pressure)

Left atrium, Left Ventricle

Four Valves

Tricuspid, Pulmonary

Mitral, Aortic


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Valves ensure blood flow is in one

direction at the correct time Blood is pumped in to arteries,

arterioles, capillaries

Blood is returned via veins to the rightheart


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Cardiac Innervation

Parasympathetic System

Slow heart rate

Reduce cardiac output

Sympathetic System

Increase heart rate

Increase force of contraction

Increase cardiac output


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Coronary Arteries

Heart muscle is supplied with oxygen and

nutrients by

Left coronary artery

Right coronary artery

The Left coronary artery supplies Left

ventricle

These arteries are narrow and highly

susceptible to obstruction


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What are the primary

cardiovascular diseases? Hypertension

Major risk factor for cardiovascular disease

Discuss later in course

Atherosclerosis

Both play a fundamental role in all othercardiovascular diseases


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Atherosclerosis

Disease of the muscular arteries (not

veins)

coronary

cerebral vessels

Progressive deposition of cholesterol

esters

Accounts indirectly for half of annual

mortality

Ischaemic heart disease MI

Cerebrovascular disease Stroke


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Lesions start as fatty streaks (aged

20years) subendothelial accumulation of large foam

cells (derived from macrophages plus SM

cells) filled with lipid

Fibrous Plaque

More advanced and the cause of disease

Develop from fatty streaks

Projects into arterial lumen

Reduced blood flow


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Most of the changes are in the intimal

layer

Accumulation of monocytes, lymphocytes,

foam cells, and connective tissue

Most of the foam cells are of smooth

muscle origin Necrotic core

Fibrous cap


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So What?

Calcification pipe like rigidity with loss

of compliance

Rupture or ulceration exposing

thrombo-genic material to circulating

blood

Vessel occlusion, angina, MI

Haemorrhage into plaque

Embolisation from plaque

Weakening of vessel wall with rupture


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Risk Factors Hyperlipidaemia

Increased levels of circulating lipids.

The higher the total or LDL cholesterol the

greater the risk of CHD and CVD

Smoking

Hypertension

Diabetes Mellitus

Homocysteinemia

The higher the levels of homocysteine the

greater the risk


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Infectious agents

herpes virus, chlamydia


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Pathogenesis of Atherosclerosis

These risk factors cause:

Endothelial Dysfunction

Injury to the endothelium is the primary event

Mechanical, tissue hypoxia,

Impair endothelial protection

decrease in plasminogen activators, heparan

sulphate, prostacyclin


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If the endothelium is damaged it no

longer serves as a barrier

LDL cholesterol passes into the intima

and accumulates and modified

(oxidised) by free radicals

Attracts monocytes and is ingested bymacrophages

Key step is attraction of monocytes and T

lymphocytes by TNF

and MCP releasedby injured endothelium and expression of

VCAM-1, ICAM


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Monocytes migrate to subendothelial

space where they become

macrophages Foam Cells Foam cells secrete PDGF, IL-1, TGF,

TNF which activate SM cells to migrate

and proliferate and deposit connectivetissue

Foam cells also release tissue factor

which is highly thrombogenic Gives rise to overlying thrombus

formation


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The Result

Atheromatous deposits

Sudden death

Peripheral vascular disease

Myocardial Ischaemia Angina

Unstable angina

MI

Cerebrovascular accidents Stroke

TIA Transient Ischaemic event


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Treatment

Statins

HMG-CoA-reductase inhibitors

Simvastatin, Pravastatin, Atorvastain

Proven benefit in the Primary and Secondary

prevention of cardiovascular disease

Reduce risk by approximately 30%

Expensive


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Documents

Cardiovascular Physio Logic Process