week 6: cardiovascular disease processes. outline structure and function of blood vessels...
TRANSCRIPT
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