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.

Fig. 8.1
Arteriosclerosis (LP).
Intimal thickening of arteries and arterioles is extremely common with increasing age. This may form part of the spectrum of atherosclerotic disease or may simply represent a physiological adaptation, which occurs with age.
Fig. 8.1 shows a small artery. Note the intima (In) is normal to the right of the image ( arrow ). The left side of the artery exhibits eccentric intimal proliferation (IP) . The thickened intima, clearly defined by the internal elastic lamina (IEL) , can be seen to consist of multiple cell layers and involves approximately half the circumference of the vessel. The media (M) and adventitia ( A) are unremarkable.

Fig. 8.2
Stages in atheroma formation.
Fig. 8.2A shows a normal elastic artery with a distinct internal elastic lamina. The artery is lined internally by a smooth, flat endothelium lying on a delicate, fibroelastic, loose connective tissue, which contains occasional multifunctional myointimal cells (tunica intima). Beneath the intima is a strong internal elastic lamina followed by a layer of smooth muscle containing some elastic fibres (tunica media). On the outer surface is the loose tunica adventitia.
Endothelial dysfunction ( Fig. 8.2B ). At certain locations in the arterial system, such as vessel branch points, turbulent flow and shear stress are associated with expression of cell adhesion factors by the endothelium, which result in the accumulation and migration of monocytes and T lymphocytes. In parallel, the endothelium may become permeable to lipoproteins.
Fatty streak ( Fig. 8.2C ). Continued endothelial dysfunction, with associated permeability to lipoproteins and monocyte and T-lymphocyte migration, produces an intimal collection of lipid- laden macrophages (foam cells) and inflammatory cells. This is followed by migration of smooth muscle from the media producing the fatty streak lesion, the earliest visible stage of atherosclerosis.
Advanced / complicated atheroma ( Fig. 8.2D ). Further progression of the early atheromatous fatty streak sees the formation of a fibrous cap between the vessel lumen and the accumulating constituents of the mature plaque, including lipid-laden macrophages, free lipid, inflammatory cells and debris. This fibrous cap forms from modified smooth muscle cells. Over time, the plaque continues to evolve, re-model and, frequently, undergoes calcification. Complications may arise from these advanced plaques through rupture (thereby exposing the highly thrombotic plaque contents), thrombosis associated with rupture, aneurysmal dilatation of the vessel or haemorrhage into the plaque, in turn leading to rupture. Thrombosis and plaque rupture usually lead to myocardial infarction in the heart and stroke in the brain.

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 .

Key to Figures

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 .

Drug Treatments for Atherosclerosis

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 ).

Key to Figures

C cholesterol clefts Cap fibrous cap F fibrous tissue FC foam cells In intima L lipid M media P fibrofatty plaque

Consequences of atheroma

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.

The main complications are shown in Figs. 8.4 to 8.7 .

Key to Figures

A atheroma F foam cells L lipid Lu lumen M tunica media T thrombus

Angiography and Stents

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.

Coronary Artery Bypass GRAFT Surgery (CABG)

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.

Key to Figures

C clot E endothelium H haemorrhage P plaque T thrombus

Fig. 8.3, Atheromatous plaque development. (A) Early atheromatous plaque (LP); (B) foam cells and lipid (HP); (C) fibrofatty plaque (LP); (D) fibrous plaque (LP).

Fig. 8.4, Complicated atheroma (MP).

Fig. 8.5, Arterial narrowing by atheroma (LP). (A) H&E; (B) EVG.

Fig. 8.6, Haemorrhage into atheromatous plaque (LP).

Fig. 8.7, Thrombus formation on atheroma (LP).

E-Fig. 8.1 H, Muscular artery. (A) H&E (MP); (B) Elastic van Gieson (MP). In muscular arteries, the elastic tissue is largely concentrated as two well-defined elastic sheets. One sheet is the internal elastic lamina IEL between the tunica intima and the tunica media. The less prominent and more variable external elastic lamina EEL lies between the tunica media M and the adventitia. The tunica intima is usually a very thin layer, not visible at low magnification, and the tunica media M is composed of concentrically arranged smooth muscle fibres with scanty elastic fibres between them. The tunica adventitia A is of variable thickness and is composed of collagen and a variable amount of elastic tissue. In larger muscular arteries, this layer may contain prominent vasa vasorum.

E-Fig. 8.2 G, Atherosclerosis. In this image, the descending aorta and the aortic bifurcation contain atherosclerotic plaque. Note the presence of complicated plaque with the aorta, just above the bifurcation. This shows ulceration and erosion, which acts as a nidus for thrombus formation. This is a common site for the formation of an abdominal aortic aneurysm.

E-Fig. 8.3 G, Atherosclerosis. This is a closer view of image E-Fig. 8.2 G in which complicated atherosclerotic plaque can be seen in more detail. There is plaque ulceration, calcification and haemorrhage. A small thrombus is present at the origin of the left common iliac artery.

E-Fig. 8.4 G, Aneurysm. In this image, the abdominal aorta has been opened posteriorly. The aorta contains a ruptured abdominal aortic aneurysm with thrombus. The aneurysm has ruptured causing retroperitoneal haemorrhage, hypovolemic shock and death.

E-Fig. 8.5 G, Anterior myocardial infarction. This is a transverse section of the heart taken just above the apex. In this image, the anterior wall of the left ventricle is haemorrhagic and soft. This patient suffered an anterior myocardial infarction several days prior to death. With increasing interval between infarction and death, the heart shows progressive yellowish softening and ultimately white scar formation.


Chapter 8 Question 1

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?


  • A)


  • B)

    Plasma cells

  • C)

    Neutrophil polymorphs

  • D)


  • E)


Chapter 8 Question 2

Which component of the atheromatous plaque is indicated by the arrow in the above image?


  • A)

    Foam cell

  • B)


  • C)


  • D)


  • E)

    Endothelial cell

Chapter 8 Question 3

Occlusion of an artery by atheromatous plaque may lead to which of the following conditions?


  • A)

    Myocardial infarction

  • B)

    Pulmonary thromboembolism

  • C)

    Venous infarction

  • D)

    Kawasaki’s arteritis

  • E)

    Coronary artery dissection

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