Week 6:Cardiovascular Disease

Processes

Outline

• Structure and function of blood vessels– Differences between arteries and veins

• Pathophysiology of atherosclerosis– Atherosclerosis and acute

cardiovascular syndromes

• Physiology of risk factors for atherosclerosis

Structure of Vessel Walls

Figure 21-1

Structure of Blood Vessels

Figure 21-2

Arteries and Pressure

• Elasticity allows arteries to absorb pressure waves that come with each heartbeat

Vasoconstriction & Vasodilatation

• The contraction of arterial smooth muscle by the ANS

• The relaxation of arterial smooth muscle• Enlarging the lumen • Affect:

– afterload on heart– peripheral blood pressure– capillary blood flow

Vascular Endothelium

Regulation of own

Permeability

Localised Vascular Control

Enzymatic Actions on

Plasma

Inflammation & Immune

Response Angiogenesis

Sensed by shear and O2 tension

Releases: NO vasdodilatory, inhibits smooth muscle proliferation, leucocyte binding, platelet aggregation.

Prostacyclin: vasodilator, inhibits plateley aggregation

ACE

Involved in white blood cell actions.

Immunoglobulins: mediate leucocyte adhesion to endothelial cells

Atherosclerosis and Arteriosclerosis

Disease Progression & Risk Factors

Atherosclerosis & Arteriosclerosis

• Atherosclerosis• ‘The formation of plaques of cholesterol,

platelets, fibrin, and other substances on the arterial walls.’

• Arteriosclerosis• Imprecise term for various disorders of

arteries, particularly hardening due to fibrosis or calcium deposition, often used as a synonym for atherosclerosis.

The Processes: Arterial Narrowing & Thrombus

Formation

LDL Cholesterol accumulates in the arterial wall & undergoes chemical changes.

Signals – endothelial cells to latch on to white blood cells.

Triggers inflammatory response LDS- foam cells

The fat-laden foam cells form a fatty streak.

Plaque grows and a fibrous cap forms to ‘heal’ the plaque.

If it breaks, the it can form a blood clot.

The fatty streak - earliest identifiable morphological change.

This is pre-dated by endothelial dysfunction

Characterised by accumulation of macrophage foam cells and a local chronic inflammatory infiltrate.

Chronic local inflammatory response.

The complex plaque is characterised by:

smooth muscle cell migration, formation of a fibrous cap,

a necrotic lipid core

increasing inflammatory infiltrate.

Plaque rupture may occur after fibrous cap weakened by the production of: degradative enzymes reactive oxygen species by the inflammatory cellular infiltrate.

Plaque rupture exposes highly prothrombotic material, that may result in the clinically recognised acute coronary syndromes.

Risk Factors

Physiological Explanations

Lipids

• Low density lipoproteins (LDLs)• Associated with endothelial injury• Taken up by macrophages• Worse when:

– glycated – oxidised

Diabetes

• Impaired endothelium-related relaxation– Via advanced glycosylation end-

products

• Increased platelet aggregation– Decreased response to a number of

agonists

Hypertension

• Reduces endothelial function (via NO)

• Increases permeability to macromolecules

• Increases growth and proliferation vascular smooth muscle cells– Via Angiotensin II

Hypertension 2

• Increases smooth muscle lipoxygenase activity oxidation of LDL inflammatory processes

• Pro-inflammatory response free radical production NO leukocyte adhesions peripheral resistance

Smoking

• Promotes endothelial dysfunction• Enhanced platelet activity• Increased whole blood viscosity

– Associated with secondary polycythaemia

• Lowers HDL, increases oxidation of LDL– Via free radical exposure

Obesity and Physical Inactivity

• Only small direct increase in atheroclerosis

• Effects via links with diabetes, hypertension and dyslipidaemia

Summary

• The general process of atherosclerotic plaque / thrombus formation

• Several physiologial risk factors for atherosclerosis

Hypertension

The Silent Killer

Hypertension• Primary (essential)

• Secondary– Tumor, kidney disorder, adrenaline gland

disorder• ADH, renin, aldosterone, adrenaline, ACE.

Effect of obesity

• When metabolised abdominal fat releases more triglycerides per g

Valvular Disorders

Common Examples

Mitral stenosis

• Narrowing of mitral valve opening due to progressive scarring

• Rheumatic Fever

• Atrial remodelling– >50% AF

• Pulmonary Hypertension

Mitral StenosisLeads to obligatory increases in pulmonary arterial pressure

Reactive arteriolar constriction and structural changes in pulmonary artery (fibrosis)

Sustained >70 mm/Hg pressuresRV hypertrophy - increased afterload

Mitral Regurgitation

• Leaky Mitral Valve

• Breathlessness• Heart Murmur• Ultrasound

• Tolerated for years due to compensation

Causes of Mitral Regurgitation

• Rheumatic fever• Mitral valve prolapse syndrome • Hypertrophic cardiomyopathy• Myocardial infarction

– Damage to ventricle where the chordae are attached.

– Can cause rupture of the chordae

• Some congenital heart problems• Infection of the valve (endocarditis)

Cardiac Myopathy and (Congestive) Heart Failure

Cardiac Myopathy

• Disorder of the heart muscle• Usually an enlargement of:

– Chambers (dilated)– Muscle tissue (hypertrophic)

• Systolic myopathies

• But may be simply due to stiffening of myocardium

• Diastolic myopathy

Causes of Cardiomyopathy

• Mostly idiopathic• Alcohol• Pregnancy• Viral – myocarditis

• MI• Valvular disorders• Secondary to hypertension

Hypertrophic or Dilated Cardiomyopathy

(Chronic) Heart Failure

• Cardiomyopathies are commonly compensatory mechanisms

• (C)HF is failure to meet Q-demands• Outcomes:• Sudden Death• Pump Failure• Transplantation

Congestive Heart Failure

• Left sided failure: increased pulmonary circuit pressure

• Pulmonary hypertension• Fluid in lungs

– (congestion)

• Common to diagnose this way

Signs to look out for

• Shortness of breath on exertion• Weight gain• Peripheral fluid retention• Chronic ‘bronchitis’

Getting to Heart Failure

• HF occurs after an accumulation of problems that may include:– Idiopathies, Viruses, drugs

• More commonly in CR secondary to:– Valvular disorders– Hypertension– MI