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Dorchester Center, MA 02124
The cardiovascular system includes the heart, blood vessels and circulating blood and is often referred to as the circulatory system. In this chapter, we will focus upon diseases affecting the blood vessels (the arteries and veins) and the heart.
The most common pathological abnormality of the arterial tree is thickening and hardening of the walls, known as atherosclerosis (see Ch. 8 ). Among the risk factors for atherosclerosis are hypertension and diabetes mellitus. In both cases, specific vascular changes may be recognised, often superimposed on the changes of atherosclerosis. Some of the important arterial wall changes associated with hypertension are illustrated in this chapter in Figs 11.1 and 11.2 and in relation to the kidney in Fig. 15.13 .
E internal elastic lamina H hyaline In tunica intima M tunica media P proteinaceous material
Abnormal dilatations of the heart or blood vessels are known as aneurysms . In clinical practice, aneurysms are most often encountered in relation to the aorta, ventricular wall of the heart or vessels of the base of the brain. In respect of aortic aneurysms, most are due to atherosclerosis, where the aortic wall is excessively thinned as a consequence of destruction of the tunica media. Table 11.1 lists the types of aneurysm, their aetiology and their most common sites of involvement. The main complications of an aneurysm are rupture, leading to haemorrhage, and thrombus formation, leading to occlusive or embolic phenomena (see Ch.9 ).
A tunica adventitia AC anterior cerebral artery Ad adventitia C communicating branch E internal elastic lamina H haematoma In tunica intima M tunica media Md medial degeneration S saccular aneurysm W wall of aneurysm
|Type||Common sites||Aetiology||Common effects of rupture|
|Atherosclerotic||Abdominal aorta||Weakening of tunica media owing to atheroma||Massive haemorrhage into retroperitoneum and peritoneal cavity|
|Saccular ( Fig. 11.4 )||Cerebral arteries||Developmental defects in tunica media and elastic laminae||Subarachnoid haemorrhage|
|Microaneurysms||Brain, retina||Hypertensive and diabetic small vessel disease||Brain and retinal haemorrhages|
|Mycotic (infective) aneurysms||Any arterial vessels||Destruction of tunica media by infected thrombus||Haemorrhage from affected vessel|
|Syphilitic (Fig. 5.11)||Ascending aorta||Damaged tunica media owing to syphilitic arteritis||Massive haemorrhage into mediastinum and thoracic cavity|
Inflammation of the walls of blood vessels may occur in arteries (arteritis) , capillaries (capillaritis) or veins ( phlebitis , venulitis ); the collective term is vasculitis . The classification of this group of disorders reflects an increasing understanding of the underlying pathogenic mechanisms.
Direct infection: Some cases of vasculitis arise from direct infection of the blood vessel wall, for example syphilitic aortitis (see Fig. 5.11) and Aspergillus infection.
Damage to vessels: Vascular injury and resulting inflammation may be caused by direct damage to vessels, such as mechanical trauma and radiation injury.
Immunological: The most common types of vasculitis are caused by a variety of immunological mechanisms, including:
The deposition of circulating immune complexes in the walls of blood vessels, as in Henoch – Schönlein purpura and post-infectious glomerulonephritis .
Direct damage to vessel walls by antibodies that react with endothelial cells ( Kawasaki’s syndrome , systemic lupus erythematosus ) or glomerular basement membrane (Goodpasture’s syndrome) .
Vasculitides associated with antineutrophil cytoplasmic antibody (ANCA) such as granulomatosis with polyangiitis (previously known as Wegener’s granulomatosis) and microscopic polyarteritis ( Fig. 11.7 ).
Idiopathic: In some cases, the pathogenesis is unknown. In giant cell arteritis ( Fig. 11.5 ) and Takayasu’s arteritis the underlying process may be an abnormality of cell-mediated immunity. Another major type of vasculitis, polyarteritis nodosa ( Fig. 11.6 ), probably belongs to the immunological group, but its aetiology remains unclear.
There are a variety of malformations and tumours that arise from vascular channels. The commonest among these are haemangiomas ( E-Fig. 11.2 G ), often regarded as hamartomas or developmental abnormalities ( Fig. 11.8 ). Clinically, benign vascular malformations in the brain are of importance as there is a risk of spontaneous intracerebral haemorrhage. Often, such malformations are composed of both arterial and venous channels and are termed arteriovenous malformations ( Fig. 11.9 ).
True neoplasms arising from blood vessels are rare and range from the benign glomus tumour ( glomangioma ; Fig. 11.10 ) to malignant tumours such as Kaposi’s sarcoma ( Fig. 11.11 ) and angiosarcoma ( Fig. 11.12 ). Kaposi’s sarcoma is associated with human herpesvirus 8 (HHV-8) infections and can be seen in patients with immunosuppression, e.g. secondary to HIV infection.
C lymphocytes and plasma cells D nuclear dust E internal elastic lamina Fi fibrous thickening Fn fibrinoid necrosis Fs fibrous stroma G giant cell H haemorrhage L liver parenchyma S vascular space T fibrin thrombus V vessel wall
A arterial channel B brain parenchyma F fat Fs fibrous stroma S stromal cells Sc sheets of tumour cells V venous channel Vs vascular space
Of the diseases involving the heart, ischaemic heart disease is the most important in developed countries. In almost all cases, the cause of ischaemic heart disease is atherosclerosis of the coronary arteries, with or without accompanying thrombosis. Coronary artery atheroma and thrombosis are illustrated in Fig 8.5, Fig 8.7 , and the stages of myocardial infarction are shown in Fig. 10.2 .
A common consequence of coronary artery disease, myocardial infarction is a leading cause of morbidity and mortality in developed countries. Typical symptoms are of central chest pain, often described as tight or pressing, which may radiate to the left arm or jaw. A variety of symptoms, including nausea, vomiting, breathless and sweating, often accompany this chest pain.
The clinical diagnosis of myocardial infarction rests on the demonstration of elevated levels of proteins released into the blood as a result of damaged myocytes (troponin) , combined with typical electrocardiographic changes. In some patients, especially those with diabetes mellitus, the typical chest pain can be absent and patients may present late with complications, the so-called ‘silent’ myocardial infarction.
Treatment is directed towards establishing reperfusion of the ischaemic segment of myocardium as rapidly as possible to minimise the volume of infarcted tissue (see clinical box ‘Angiography and stents’ in Ch. 8 ).
Complications of myocardial infarction include sudden death, arrhythmia, cardiac failure, ventricular rupture, rupture of papillary muscles with acute valve failure and mural thrombus with potential for thromboembolisation. Some of these complications may arise in the immediate aftermath of the infarction (acute-phase complications) and some may develop some time later.
The cardiomyopathies are disorders of the heart muscle resulting in disturbance of heart function (often described as systolic or diastolic dysfunction). A classification of cardiomyopathies is shown in Table 11.2 . The abnormalities usually cause progressive cardiac failure, but sudden cardiac death caused by acute arrhythmia may be the first manifestation.
|Dilated cardiomyopathy||Defective myocardial contractility leading to ventricular dilation and cardiac failure||Inherited, alcoholism, peripartum|
|Hypertrophic cardiomyopathy ( E-Fig. 11.3 G )||Hypertrophy of the interventricular septum leading to outflow obstruction||Inherited|
|Arrhythmogenic cardiomyopathy||Abnormal thinning of the right ventricular wall due to fibrosis and adipose tissue deposition||Inherited|
|Infiltrative/restrictive cardiomyopathy||Failure of the myocardium to relax due to abnormal infiltrate||Amyloidosis, others|
Other cardiomyopathies can be acquired, such as those seen in patients with alcoholism, severe vitamin deficiency ( beriberi ) or following an episode of myocarditis.
Some diseases of the heart muscle may be related to inherited enzyme deficiencies such as Fabry disease and glycogen storage disorders .
An infiltrative cardiomyopathy can be caused by deposition of amyloid (see Ch. 15 ) between the cardiac myocytes. This causes progressive cardiac failure due to a restriction of cardiac function.
A mature adipose tissue Am amyloid D disarray F fibrosis M cardiac myocytes V vacuolar change
Inflammation may affect the pericardium, myocardium or endocardium, either separately or concurrently. The causes are numerous, but the most common are ischaemia and infection. Most infections of the pericardium (pericarditis) and myocardium (myocarditis) are viral, whilst those of the endocardium (endocarditis) and valves (valvulitis) may be bacterial ( Fig. 11.18 ) or fungal.
The main causes of pericarditis are summarised in Table 11.3 . The histological features of most forms of acute pericarditis are virtually identical, whatever the cause, and are illustrated and discussed in Fig. 3.4. In tuberculous pericarditis, there is a chronic granulomatous response as described in Ch. 5 . In malignant pericarditis, clumps of tumour cells are often mixed with the inflammatory exudate.
|Myocardial infarction||After transmural myocardial infarction||Common|
|Cardiac surgery||After surgical opening of pericardial sac||Common|
|Viral infections|| Usually young adults.
Coxsackie B virus most common
|Malignancy||Local invasion or metastatic tumour deposits||Uncommon|
|Bacterial infections||Secondary to lung infection, including TB||Uncommon|
|Rheumatic fever||Part of rheumatic pancarditis||Rare|
|Hypertension||Abnormally raised blood pressure|
|Essential hypertension||Walls of small muscular arteries thickened. Hyaline arteriosclerosis in arterioles.||11.1|
|Accelerated hypertension||Severe ‘onion skin’ thickening of tunica intima of small muscular arteries. Rapid proliferation of intima with accompanying fibrinoid necrosis.||11.2|
|Aortic dissection||Most commonly thoracic aorta. Medial haematoma forms following laceration of intima. Almost all cases show cystic medial necrosis.||11.3|
|Aneurysms||Variety of types summarised in Table 11.1||Table 11.1|
|Saccular (berry)||Develop from cerebral arteries. Manifest in middle age as common cause of non- traumatic subarachnoid haemorrhage.||11.4|
|Vasculitis||Classified by presumed aetiology as direct spread of infection, direct trauma to vessel, immune mediated or idiopathic|
|Giant cell arteritis||Commonest systemic vasculitis in adults. Most often involves medium-sized vessels of head and neck. Cause unknown. Inflammatory cell infiltrate in vessel wall, including multinucleated giant cells.||11.5|
|Polyarteritis nodosa||Systemic vasculitis of small muscular arteries. Neutrophil-rich inflammatory cell infiltrate with associated fibrinoid necrosis of vessel wall. Small aneurysms may form in relation to weakened vessel wall.||11.6|
|Microscopic polyarteritis||Immune-mediated reaction to variety of agents. Typically, neutrophil infiltrate in walls of small vessels.||11.7|
|Tumours of blood vessels||Common forms benign. Rarer malignant forms.|
|Haemangioma||Benign tumour of vessels subdivided as capillary or cavernous depending on size of vascular channels.||11.8|
|Arteriovenous malformation||Most often arise in association with superficial vessels of brain and may give rise to neurological symptoms and/or haemorrhage. Irregular vascular channels interspersed among reactive brain tissue.||11.9|
|Glomus tumour||Small, painful, raised lesion most commonly on the digits.||11.10|
|Kaposi’s sarcoma||AIDS-defining lesion. Causative agent is HHV-8 in majority. Sheets of stromal cells interspersed with irregular vascular spaces.||11.11|
|Angiosarcoma||Approximately 50% arise in head and neck. Malignant. May metastasise to local lymph nodes. Atypical endothelial cells to undifferentiated spindle cells with irregular vascular spaces.||11.12|
|Ischaemic heart disease||See Ch. 8 (Atheroma) and Ch. 10 (Infarction)|
|Cardiomyopathy||Myocardial dysfunction. Various causes, but many are genetically inherited.||Table 11.2 , Fig. 11.13|
|Inflammation of the heart||May affect pericardium, myocardium, endocardium.|
|Pericarditis||Inflammation of pericardium. Variety of causes.||3.4C|
|Myocarditis||Most often a viral aetiology, but may be bacterial, immune mediated, drug related or idiopathic. Inflammatory cell infiltrate between myocytes with myocyte destruction.||11.14|
|Rheumatic fever||Manifestation of systemic inflammatory disease following streptococcal throat infection. Rheumatic carditis: characteristic Aschoff bodies in myocardium, particularly subendocardial/subpericardial locations. Acute rheumatic endocarditis: inflammation of heart valves with formation of thrombotic vegetations.|| 11.15
|Marantic endocarditis||Non-bacterial endocarditis most commonly associated with systemic illness (e.g. disseminated malignancy). Friable, thrombotic vegetations form on valves.||11.17|
|Acute bacterial endocarditis||Usually complicates systemic sepsis with virulent organism. Can arise on otherwise normal valve. Vegetation forms composed of fibrin containing colonies of causative organism.||11.18|
|Cardiac tumours||Primary cardiac tumours rare, with majority benign.|
|Atrial myxoma||Benign tumour of unknown histogenesis. Small proportion autosomal dominant as part of Carney’s complex. Stellate cells and atypical vascular spaces in a myxoid matrix.||11.19|
The term myocarditis implies inflammatory damage to the myocardium and, by common usage, usually excludes the acute inflammatory reaction to necrotic muscle fibres seen in myocardial infarction (Fig. 10.2). Primary myocarditis can be associated with viral infections, rheumatic fever and exposure to certain toxins and drugs. In some cases, no causative factor can be identified (idiopathic myocarditis) .
Endocarditis and valvulitis involve not only inflammation, but also thrombus deposition on the endocardium and/or valves. These are important diseases and have a high mortality rate, their clinical manifestations often resulting from embolic phenomena or from dysfunction of the valves.
Rheumatic fever is a systemic inflammatory disease that, in susceptible individuals, follows several weeks after a group A β-haemolytic streptococcal throat infection. The systemic manifestations represent a disordered immunological response resulting in inflammation of connective tissues. All parts of the body may be involved, for example the joints and skin, with painful short-term consequences. Involvement of the heart is of great clinical importance because of potentially fatal acute myocarditis and endocarditis and the long-term consequences of chronic scarring of the heart valves ( E-Fig. 11.6 G ).
A Anitschow myocyte D degenerate material I inflammatory cells M myocytes V thrombotic vegetation
The heart valves may become subject to a variety of vegetative lesions that have traditionally been described as forms of endocarditis . The primary phenomenon underlying all these conditions is the formation of thrombus on the valve leaflets or cusps.
As in the arterial system, roughening of the endocardial surface predisposes to thrombus formation ( Ch. 9 ). This may occur when valve leaflets or cusps have been previously damaged by rheumatic fever or are congenitally abnormal. Thrombus formation may also follow autoimmune valve damage in systemic lupus erythematosus (Libman–Sacks endocarditis) and in the acute phase of rheumatic fever ( Fig. 11.16 ). The most frequent type of valve thrombus, however, occurs in so-called marantic endocarditis ( Fig. 11.17 ), in which warty, thrombotic vegetations develop on mitral and aortic valves. This phenomenon occurs in seriously ill patients, often those with widely disseminated malignancy, and is usually associated with a hypercoagulable state. Despite use of the term endocarditis in these conditions, inflammation is usually not a feature of the valve at the time of thrombus formation.
True valvular inflammation may arise, however, if these thrombotic vegetations on valves then become infected with bacteria, fungi or other organisms, conditions collectively referred to as infective endocarditis . Bacterial endocarditis tends to be divided into two clinicopathological patterns. In the first, traditionally known as subacute bacterial endocarditis , the thrombotic vegetations develop on previously damaged valves, which then become colonised by bacteria of low virulence such as Streptococcus viridans . Such organisms tend to reach the valves via a transient bacteraemia, for example following dental extraction. The major clinical consequences are those resulting from detachment of small thrombotic emboli, often infected, into the systemic circulation.
In the second type of bacterial endocarditis, known traditionally as acute bacterial endocarditis ( Fig. 11.18 and E-Fig. 11.8 G ), thrombi form on previously normal valves and become infected by virulent organisms such as Staphylococcus aureus . In this case, the patient is usually already severely debilitated and septicaemic, for example from an infected urinary catheter, and the infecting organism is responsible for the septicaemia. In contrast with the subacute pattern, in the acute form the fulminating infection extends into the substance of the valve, causing tissue necrosis. Rapid destruction of the valve leaflet leads to valvular incompetence, with acute cardiac failure as the usual clinical outcome.
Fungal endocarditis, formerly rare, is now appearing more commonly as a complication of immunosuppressive therapy, intravenous drug abuse or AIDS. Candida albicans (Fig. 5.15) is the most common organism.
Whilst metastases to the pericardium and heart are not infrequent in the late stages of systemic malignancies, primary tumours of the heart are rare, the vast majority being benign. Of these, myxomas are the most common primary cardiac tumours occurring in adults ( Fig. 11.19 ). In contrast, in children, the commonest primary tumours encountered are rhabdomyomas , which are often multiple, present in infancy and have a strong association with tuberous sclerosis . Other tumours that may arise in the heart include lipomas, fibromas and angiosarcomas.
B bacteria F fibrin In inflammatory cells L valve leaflet M myxoid matrix S stellate tumour cells T thrombus V abnormal vascular channel