304 North Cardinal St.
Dorchester Center, MA 02124
304 North Cardinal St.
Dorchester Center, MA 02124
The wall of an artery has three layers, the intima, media and adventitia, which are separated from each other by thin elastic fibres known as the elastic laminae ( E-Fig. 8.1 ). The intima, the innermost layer, is composed of fibroelastic tissue and is lined by a thin layer of endothelial cells along its luminal aspect. The media contains bundles of smooth muscle and is separated from the intima by the internal elastic lamina ( Fig. 8.2A ). The adventitia is composed of collagen and is separated from the media by the external elastic lamina. In larger arteries, the adventitia also contains the vasa vasorum, the blood vessels which supply blood and nutrients to the arterial wall. This combination of smooth muscle, elastin and collagen permits alteration in vascular tone.
With age, the relative proportions of these components alter, resulting in a loss of elasticity and thickening of the vessel of wall due to an increase in collagen deposition and smooth muscle hypertrophy within the intimal layer. This process, commonly referred to as arteriosclerosis (derived from the Greek arteria , meaning artery, and skleros meaning hardening) is often used as a general descriptive term for such diseases. Arteriosclerosis can often be identified in patients with hypertension and can be seen in the arterioles within the kidney in these patients (see Figs. 11.1 and 11.2 ). It is illustrated in Fig. 8.1 .
A adventitia IEL internal elastic lamina In intima IP intimal proliferation M media
Atheroma (from the Greek word for porridge or gruel) affects the intima and media of large and medium-sized arteries and is the commonest type of arteriosclerosis, referred to as atherosclerosis ( E-Figs. 8.2 and 8.3 ). It is a chronic inflammatory process affecting susceptible individuals. It is a very common condition in developed societies and contributes to a large proportion of deaths. A variety of modifiable risk factors (those we can influence/control) and non-modifiable risk factors (those we have no control over) are important in the causation of this disease; these are summarised in Table 8.1 .
Statins : These are a group of drugs that act by inhibiting an enzyme involved in the production of low-density lipoprotein (LDL) cholesterol, which transports cholesterol to arteries where it can be incorporated as atheroma. Blocking the enzyme results in increased LDL receptor expression in the liver and, as a consequence, an increased clearance of LDL from the blood with associated decrease in blood cholesterol levels. There is some evidence to suggest that statins also reduce cardiovascular risk by other mechanisms.
Aspirin/clopidogrel : These drugs both act to inhibit platelet aggregation and reduce the risk of thrombosis.
Anti-hypertensives : Close control of blood pressure is important in patients with increased cardiovascular risk. High blood pressure can be controlled by anti-hypertensive medications.
Diabetic control : Poorly controlled diabetes mellitus is a risk factor for progressive atherosclerosis. Diabetic patients may take medications such as gliclazide, metformin or insulin injections to adequately control diabetes mellitus. This can be monitored using an HbA1c test to reveal what percentage of haemoglobin is bound to excess sugars within the blood ( glycosylated ).
C cholesterol clefts Cap fibrous cap F fibrous tissue FC foam cells In intima L lipid M media P fibrofatty plaque
All arterial vessels may be affected by atherosclerosis. The most commonly affected vessels are the coronary arteries (resulting in angina or myocardial infarction), the aorta (contributing to the formation of aneurysms) and the cerebral arteries (resulting in stroke).
The most important pathological and clinical sequelae of atherosclerosis are as follows:
Occlusion: Narrowing of the arterial lumen produces partial or complete obstruction to blood flow; this may result in ischaemia and infarction of the tissue supplied by the atheromatous vessel (see Ch. 10 ).
Thrombosis: When there is shear stress within the lumen of a blood vessel due to turbulent blood flow, endothelial disruption or ulceration can result. This can act as a nidus for the formation of a thrombus , an aggregate of platelets and fibrin within the lumen of a vessel wall (see Ch.9 ). Thrombus can obstruct the vessel wall leading to infarction of the tissue supplied (see Ch.10 ). In some cases, the thrombus can detach and travel with circulating blood, along the blood vessel (embolism) . This can result in the obstruction of blood vessel lumen distal to the embolus (see Ch. 9 ).
Aneurysm: Loss of smooth muscle and elastin from the media of an artery causes weakening of the vessel wall, predisposing to a localised area of dilatation. This is referred to as an aneurysm ( E-Fig. 8.4 G ). As an aneurysm increases in diameter, the wall thins and the risk of rupture increases (according to the law of Laplace). Rupture of the aneurysm can lead to fatal haemorrhage, most commonly seen in the abdominal aorta (so-called ruptured abdominal aortic aneurysm). Aneurysms may also lead thrombus formation (see Ch. 9 ) due to blood stasis and endothelial disruption within the aneurysmal cavity.
A atheroma F foam cells L lipid Lu lumen M tunica media T thrombus
Where a vessel is narrowed by atheroma, typically a coronary artery, it is possible to visualise the narrowed segment by a process known as angiography .
During angiography, a catheter is passed along the systemic arterial system from a peripheral vessel (such as the femoral artery) to the diseased coronary artery. Once at the site of narrowing, the vessel can be visualised using contrast dye injections. If there is significant narrowing, then a stent can be deployed. This acts as a scaffold to keep the narrowed artery open. Some stents can contain medication, which is supplied directly to the site of arterial disease; these are known as a drug eluting stents . Research is currently focused upon stent structure and composition in order to improve their function and longevity.
Where atheroma in a coronary vessel is such that symptoms from the reduced flow through the stenotic segment cannot be controlled by medication and/or a stent procedure, it is possible to perform surgery to bypass the blocked segment of vessel. This is achieved by utilising a nearby vessel (e.g. internal thoracic artery) or inserting a length of vessel from elsewhere in the body (e.g. a vein from the leg) between the aorta and the diseased vessel beyond the point of stenosis. This length of vessel is sometimes referred to as the graft . Hence, the procedure is commonly referred to as a coronary artery bypass graft or, more often, by its acronym as a CABG (pronounced ‘cabbage’).
Whilst angioplasty and stenting may be favoured for disease in a single coronary vessel, bypass surgery is preferred where more than one vessel is diseased. Hence, the number of vessels bypassed may be referred to when discussing the procedure (e.g. double bypass, triple bypass ).
Together, the procedures of angioplasty, stenting and bypass surgery are referred to as re-vascularisation procedures. Although these procedures have transformed outcomes in patients with coronary artery atheromatous disease, it should be borne in mind that while they may overcome the diseased arterial segment, they do not prevent further atheroma from developing. As such, following re-vascularisation, it is advised that patients do all they can to tackle the modifiable risk factors that may have contributed to the development of their atheromatous disease.
C clot E endothelium H haemorrhage P plaque T thrombus
A man presents with central chest pain radiating to his left arm. He is diagnosed with a myocardial infarction and dies two weeks later. At post mortem examination, a histological section from the area of infarction shows that the necrotic myocardium has largely been replaced by capillaries, fibroblasts and collagen. Which of the inflammatory cells in this lesion has the most important role in the healing process?
Which component of the atheromatous plaque is indicated by the arrow in the above image?
Occlusion of an artery by atheromatous plaque may lead to which of the following conditions?
Coronary artery dissection