Atherosclerosis (also called atheroma) is an inflammatory, degenerative disease of large and medium-sized arterial vessels. It is characterised by the development of fibrolipid plaques within the intima of the vessel wall. In smaller arteries, including the coronary vessels that supply the myocardium, these plaques can cause severe narrowing (stenosis) of the lumen, with significant impairment of blood flow. The clinical consequences depend on the speed of development of the stenosis, and on whether the affected tissue has any additional source of blood supply (known as collateral supply). In large arteries, such as the abdominal aorta, the inflammatory atherosclerotic process also damages the muscular wall causing weakness and dilatation. This is known as aneurysm formation (see Box 17). As the aneurysm enlarges there is an increasing risk of rupture, with resultant catastrophic haemorrhage.

Four major risk factors are recognised for atherosclerosis:

Minor risk factors include increasing age, male sex, obesity, family history and stress.

Atheromatous plaques are probably initiated by injury to the endothelial cells of the arterial intima. An inflammatory response is evoked to the damage, which results in an infiltrate of macrophages, and proliferation of smooth muscle cells from the media of the vessel wall. These smooth muscle cells migrate into the intima and begin to produce collagen. Both the macrophages and the smooth muscle cells may accumulate lipid within their cytoplasm, giving a vacuolated appearance on light microscopy (‘foam cells’). Free cholesterol and necrotic inflammatory debris also become incorporated within the plaque lesion.

Figure 33 shows a normal muscular artery and a typical atheromatous plaque with a fibrous tissue cap and a lipid-rich, necrotic centre. It is important to realise that the actual composition of individual plaques varies, and can change over time. Plaques that are particularly rich in lipids may be more unstable and susceptible to rupture or haemorrhage. Older plaques can become heavily calcified. The plaque surface is prone to develop superimposed thrombosis, which can rapidly increase the severity of the obstruction to blood flow. At autopsy, it is common to find a recent thrombus complicating an atheromatous coronary artery plaque in patients who died after acute myocardial infarction.

Aortic dissection is also called dissecting aneurysm, although this is an inaccurate term as the aorta is not significantly dilated. In aortic dissection, blood tracks into the muscular wall of the blood vessel. The entry point of blood into the aortic media is through an intimal tear, usually within the proximal 10cm of the ascending aorta. Occasionally, there is a second distal luminal tear, through which blood re-enters the circulation, producing a ‘double-barrelled’ aorta. More commonly, however, the haemorrhage extends outwards with vessel rupture and catastrophic extramural haemorrhage into:

• the pericardium, causing cardiac tamponade

• the mediastinum, causing haemothorax

• the abdominal cavity (haematoperitoneum).

The dissection can also involve the great vessels of the neck, compromising cerebral blood flow. Dissection of the coronary arteries is a rare cause of acute myocardial ischaemia.

There is a strong association with systemic hypertension and with Marfan’s syndrome.

Ischaemia is due to lack of oxygen, and in the overwhelming majority of ischaemic heart disease (IHD) cases this is due to reduced blood flow through coronary arteries narrowed or occluded by atherosclerosis. However, the left ventricular myocardium is also at risk of ischaemia when there is pathological hypertrophy, for example in systemic hypertension or aortic valve stenosis. Under these conditions, cardiac perfusion may be insufficient to meet the metabolic needs of the increased muscle mass. Rarely, cardiac ischaemia can result from decreased oxygen-carrying capacity of the blood in severe anaemia (even though the coronary arteries may be normal).

Chronically raised systemic blood pressure is a major cause of morbidity and mortality. Hypertension can cause, or significantly contribute to:

‘Normal’ blood pressure varies within a population and with age, but evidence suggests that a sustained pressure of 140/90mmHg or greater is associated with increased risk of disease. Persistent diastolic blood pressure in excess of 100mmHg requires treatment. Very high blood pressure (e.g. 240/120mmHg) can result in accelerated disease – ‘malignant hypertension’.

In approximately 10% of cases, systemic hypertension is secondary to another disease (Box 18). The mechanism of primary hypertension is unclear but the following defects have been found in patients:

Family history, obesity and excessive alcohol intake are further associated factors. The aetiology of essential hypertension is complex and clearly involves a combination of genetic and environmental factors. Modest, but clinically significant, reductions in blood pressure may be achieved by weight loss, regular physical exercise, moderation of alcohol intake and possibly by reduction of salt in the diet.

Cardiomyopathy is defined as heart muscle disease not caused by ischaemic, hypertensive, valvular or congenital heart disease. Although uncommon, cardiomyopathies are an important cause of cardiac failure and sudden death in young adults. The aetiology of specific cardiomyopathies is shown in Box 19. Ninety per cent are of the dilated type.

Myocarditis is inflammation of the heart muscle. It may be asymptomatic, or cause:

Acute myocarditis may be suggested at autopsy by a pale, flabby heart, but histological examination is necessary for diagnosis. Microscopically there is multifocal myocardial chronic inflammation associated with death of the cardiac muscle cells. The aetiology of myocarditis is shown in Box 20.

The aorta emerges from the right ventricle and the pulmonary artery arises from the left ventricle. To be compatible with post-natal life, there must also be either an atrial or ventricular septal defect.

Damage to the cardiac valves can result in stenosis (narrowing of the valve orifice with obstruction to blood flow) or incompetence (regurgitation of blood back through a leaking valve). Valve disease can be congenital (see Section 14.3) or acquired. In non-congenital cases the clinically important lesions almost always affect the mitral or aortic valves.

Abnormal movement of deformed valves and abnormal blood flow causes characteristic murmurs and added sounds on cardiac auscultation.

Rheumatic heart disease (RHD) is a major cause of acquired mitral valve disease. The incidence has dramatically decreased in the UK over recent decades but is still relatively common in the developing countries. The initiating event is usually a pharyngeal infection by group A β-haemolytic streptococci, followed several weeks later by rheumatic fever, an immunologically mediated multisystem disorder. Rheumatic fever (RF) results from the cross-reaction of antistreptococcal antibodies with normal host tissues – direct bacterial infection does not occur. During acute RF there is often a pancarditis with inflammation of pericardium, myocardium and endocardium. Myocarditis can occasionally cause acute heart failure, arrhythmias and death. However, it is recurrent attacks of rheumatic fever that produce the most significant cardiac lesions. Repeated acute inflammation of the endocardium covering heart valves leads to fibrosis and deformity. Valve leaflets become thickened and fused, resulting in ‘fishmouth’ or ‘buttonhole’ mitral valve stenosis. The aortic valve may also be affected. Complications include:

Mitral valve prolapse, also known as ‘floppy mitral valve’, is a common condition involving approximately 5% of adults. Young females and individuals with Marfan’s syndrome are particularly affected. One or both mitral valve leaflets are enlarged and prolapse into the left atrium during systole. The condition is usually incidental but occasionally can cause mitral regurgitation, infective endocarditis, valvular thrombosis or arrhythmias.

Infection of the endocardium or vascular endothelium can occur in:

Infective endocarditis (see also Box 21) is usually a chronic/subacute illness caused by low-virulence organisms colonising abnormal tissue. Normal heart valves can be infected by high-virulence bacteria or fungi, especially in intravenous drug users or immunosuppressed individuals (those with acquired immune deficiency syndrome (AIDS) or diabetics, alcoholics, transplant recipients).

The causes and consequences of valvular heart disease are summarised in Table 19.

Left ventricular failure results from a loss of myocardial contractility, due to the sudden or gradual dysfunction, or death, of cardiac muscle cells. Less frequently, there may be marked impairment of ventricular filling during diastole. The latter situation occurs when the left ventricular wall is abnormally ‘stiff’ and unable to distend adequately.

Right ventricular failure is most often encountered as a consequence of left ventricular dysfunction. Myocardial infarction only infrequently involves the right side of the heart, and then this is usually as an extension of a predominantly left ventricular infarct. Primary right ventricular failure can occur as a result of chronic lung disease. The right ventricle is spared the effects of systemic hypertension. However, raised pressure in the pulmonary circulation will affect the right ventricle, causing hypertrophy. This is recognised by the pathologist at post mortem by an increase in the thickness of the right ventricular wall, which is normally less than 5mm, and an increase in isolated right ventricular weight (normally less than 50–60g; total heart weight depends on sex and body weight, but is usually 250–350g in the absence of any cardiac disease). Lung diseases causing pulmonary hypertension include:

• pulmonary embolism

• obstructive lung diseases

• interstitial lung diseases.

In left ventricular failure, these changes first appear in the pulmonary circulation. Back-pressure is transmitted through pulmonary veins into the alveolar capillaries of the lungs. Thus, oedema develops first in the pulmonary air spaces, causing shortness of breath. Patients dying with pulmonary oedema have dark-red, ‘wet’ lungs at post mortem, due to the accumulation of blood and oedema. Lung weights (normally 250–300g) are often doubled or trebled by the fluid, which is easily demonstrated when the lung surfaces are cut with a knife and the fluid squeezed out, like water from a sponge. Microscopically, ‘heart failure cells’ are often prominent – these are alveolar macrophages containing haemosiderin pigment, a marker of previous capillary haemorrhage. Fluid accumulation within the pleural cavities may produce bilateral serous effusions.

In right ventricular failure, the inferior and superior vena cavae and their feeding veins become congested. Clinically this is evident as raised jugular venous pressure in the neck. Congestion may extend into many organs, especially the liver, which becomes enlarged and shows a characteristic patchy, pale and reddish cut surface at post mortem (which pathologists like to describe as ‘nutmeg liver’). Splenomegaly is also common. Oedema develops in the dependent areas of the body, affecting the legs of seated and ambulant patients, and the sacral area in patients confined to bed. Ascites (straw-coloured fluid) may develop in the peritoneal cavity.

In severe left ventricular failure, symptoms and signs will also result from failure to adequately perfuse the systemic organs. The systemic blood pressure is decreased, the skin appears pale and cold as circulation is diverted to conserve vital organs, especially the brain. Intestinal ischaemia can result in haemorrhage or infarction. Renal ischaemia stimulates the renin-angiotensin system, causing fluid retention that may exacerbate oedema. Severe kidney ischaemia causes acute tubular necrosis and acute renal failure. In advanced heart failure, even the cerebral circulation may be compromised sufficiently to cause symptoms of confusion and diminished consciousness. The effects of low cardiac output are confounded as many patients with cardiac failure also have significant atherosclerotic disease in their major visceral arteries, which further limits blood flow to the organs.

See Chapter 6 and Figure 35.

Inflammation of blood vessels can affect arteries, veins and capillaries. The aetiology most frequently appears to be immunological, with deposition of immune complexes in vessel walls. Some vasculitides are associated with antineutrophil cytoplasmic antibodies (ANCA). These antibodies show two distinct patterns on direct immunofluorescence examination – perinuclear (p-ANCA) and cytoplasmic (c-ANCA). Over 80% of patients with Wegener’s granulomatosis have circulating c-ANCA at some stage of their disease. The pathogenetic role of ANCA is uncertain, but the antibodies are useful in diagnosis and in monitoring disease activity and the effects of treatment.

The more commonly encountered and important vasculitides are shown in Table 20. Vasculitis can also occur in connective tissue disease such as rheumatoid arthritis. Infectious vasculitis occurs when microorganisms invade blood vessels from an adjacent source of sepsis, or via haematogenous spread from distant sites of infection.