Cardiovascular system

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Atherosclerosis, aneurysms and ischaemic heart disease119

14.2 Hypertension, cardiomyopathies and myocarditis122
14.3 Congenital heart disease124
14.4 Valvular heart disease124
14.5 Heart failure125
14.6 Thrombosis, embolism and vasculitis127
14.7 Pericardial disease128
14.8 Vascular and cardiac neoplasms128

Self-assessment: questions130
Self-assessment: answers132

Chapter overview
Pathology of the cardiovascular system, the heart and blood vessels, is responsible for a large proportion of deaths in the UK each year, and also causes considerable morbidity through heart failure, stroke and peripheral vascular disease. The major underlying disease processes responsible include atherosclerosis, hypertension and diabetes mellitus. Lifestyle modification can have a significant role in reducing disease risk, particularly in relation to smoking, exercise, body weight and fat consumption. This chapter covers atherosclerosis and its complications, ischaemic heart disease, hypertension, valvular heart disease, cardiomyopathies and congenital heart disease. Many cardiac pathologies result in heart failure, which may initially primarily involve either the left or right ventricle. The basic pathology of vasculitis and vascular tumours is also reviewed.

14.1. Atherosclerosis, aneurysms and ischaemic heart disease

Learning objectives
You should:

• understand the pathogenesis and clinical consequences of atherosclerosis
• be able to discuss pathology and complications of myocardial infarction
• know how lifestyle modifications can reduce the risk of ischaemic heart disease.

Atherosclerosis

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.
Box 17

Definition. Abnormal dilatation of a vessel wall, which communicates with the lumen – almost always arterial
Pathogenesis:

• Inflammation: atherosclerotic aneurysm (abdominal aorta, iliac arteries, popliteal arteries); polyarteritis nodosa; Kawasaki’s disease (coronary arteries)
• Infection (mycotic aneurysm): syphilis; direct spread from adjacent infection
• Congenital defect: Berry aneurysm (circle of Willis, see Ch. 27)
• Metabolic: diabetes mellitus (retinal capillary microaneurysms)
• Hypertension: Charcot–Bouchard aneurysms (deep white matter of cerebral hemispheres)
• Trauma
Complications:

• Rupture with haemorrhage (often fatal if aorta or cerebral vessels involved)
• Compression of adjacent structures
• Thrombus formation (vessel occlusion and distal thromboembolism)
• Secondary infection
• Sclerosing periaortitis (dense fibrosis surrounding abdominal aortic aneurysm which can entrap ureters)
Four major risk factors are recognised for atherosclerosis:

• smoking
• hypercholesterolaemia (raised low density lipoproteins)
• hypertension
• diabetes mellitus.
Minor risk factors include increasing age, male sex, obesity, family history and stress.

Pathogenesis of the fibrolipid atherosclerotic plaque

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.

Clinical complications of atherosclerosis

Cerebral arteries: transient ischaemic attacks, stroke.
Aorta: abdominal aneurysm formation (risk of rupture and death) (see Box 17).
Mesenteric arteries: intestinal ischaemia and infarction.
Renal arteries: renal artery stenosis (hypertension, ischaemic kidney).
Lower limbs: intermittent claudication, gangrene.

Aortic dissection

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.

Ischaemic heart disease

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).

Myocardial infarction

Regional (transmural) infarction

Regional (transmural) infarction is caused by occlusion of a single coronary artery. The arterial blockage results from atherosclerosis complicated by thrombosis or by intraplaque haemorrhage, which rapidly expands the atheromatous plaque (see Figure 34). The commonest sites for clinically significant coronary atherosclerosis are:

• proximal left anterior descending artery (up to 50%)
• right coronary artery (30%)
• left circumflex artery (up to 20%)
• left main coronary artery.
Regional infarction most frequently affects part of the anterior wall of the left ventricle, or part of the interventricular septum, with extension into the right ventricle in a small proportion of cases. Isolated right ventricular infarction is very uncommon.
The subendocardial region of the myocardium is the muscle area most vulnerable to hypoxia.

Subendocardial infarction

Subendocardial infarction can occur when there is a global decrease in cardiac blood flow due to systemic hypotension (‘shock’). Myocardial necrosis is usually limited to the inner third of the muscle but can involve the territory of more than one coronary artery.
Unusual causes of myocardial infarction include coronary artery dissection, arteritis or spasm.

Macroscopic and microscopic changes in myocardial infarction

• Less than 24 hours – microscopic changes only (increased eosinophilic staining of cardiac muscle cells, loss of nuclei, muscle cells become buckled).
• From 24 to 72 hours – infarct becomes apparent macroscopically at autopsy as an area of pallor or yellow discoloration, with a peripheral rim of haemorrhage. Microscopically the dead muscle fibres provoke an inflammatory response, initially consisting of neutrophils followed by macrophages. The infarct becomes soft.
• Weeks to months – collagen is produced and the scar becomes progressively less cellular, less vascular and more fibrotic. See also brief summary on page 50 (Table 8).

Biochemical markers of myocardial infarction

Necrotic cardiac muscle releases enzymes, which can be measured in the serum and are helpful in confirming the diagnosis.

Heart-specific troponins – released 2–4 hours after cell death, remaining raised for up to 1week. Troponin T and I are highly specific for myocardial damage.
Creatine kinase (CK) – starts to rise after a few hours of infarction, and falls again within 48 hours. CK is also released from injured skeletal muscle cells; measurement of the specific cardiac isoenzyme is therefore more diagnostically helpful.
Aspartate aminotransferase (AST) – this is also non-specific as it is released by damaged liver cells.
Lactate dehydrogenase (LDH) – peaks at 3–6days and may remain elevated for 2weeks. May be useful in patients presenting late after suspicious chest pain.

Complications of myocardial infarction

Immediate:

• arrhythmias
• acute cardiac failure
• cardiogenic shock
• sudden death.
Early:

• infarct rupture (3–7days).
Late:

• mural thrombosis
• cardiac aneurysm.
Dressler’s syndrome (pericarditis associated with circulating antibodies to heart muscle) occurs from 2weeks to 2years after infarction.
Reinfarction can occur at any time. Cardiac failure and arrhythmias may also be late complications. The presence of myocardial scarring increases the risk of sudden death from ventricular arrhythmia.

14.2. Hypertension, cardiomyopathies and myocarditis

Learning objectives
You should:

• know the aetiology, risk factors and complications of hypertension, so as to be able to identify patient risk factors amenable to treatment by lifestyle modification, and to investigate patients appropriately for causes of secondary hypertension
• understand the term cardiomyopathy, its classification, major causes and complications.

Hypertension

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

• atherosclerosis
• hypertensive heart disease (left ventricular hypertrophy)
• chronic renal failure
• cerebrovascular disease (intracerebral haemorrhage, ruptured Berry aneurysm)
• retinopathy.
‘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:

• abnormal renal excretion of sodium
• abnormal sodium and calcium metabolism in vascular smooth muscle
• abnormalities of renin-angiotensin mechanism, probably in part related to polymorphisms in key genes.
Box 18

Renal disease:

• Glomerulonephritis
• Polycystic kidney disease
• Renal artery stenosis
• Chronic pyelonephritis
• Renal cell carcinoma
Endocrine disease:

• Adrenal cortical tumours
• Cushing’s disease
• Phaeochromocytoma
• Diabetes mellitus
• Acromegaly
Coarctation of the aorta
Iatrogenic:

• Steroid treatment
Note that hypertension can be either a cause or a consequence of chronic renal impairment.
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

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.
Box 19

Genetic:

• Hypertrophic cardiomyopathy (HOCM)
• Haemochromatosis
Post-infectious:

• Dilated cardiomyopathy (many cases are probably caused by viral infection)
Toxic:

• Alcoholic cardiomyopathy
• Drug induced (chemotherapy agents)
Metabolic:

• Amyloid heart disease
Idiopathic

Hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HOCM) is characterised by asymmetrical left ventricular hypertrophy (as opposed to the concentric hypertrophy seen in hypertensive heart disease and aortic valve stenosis). The interventricular septum is particularly thickened. Microscopically, the cardiac muscle cells are enlarged and haphazardly organised (myocyte disarray). There is often fibrosis between muscle cells. Many cases show autosomal dominant inheritance. Genetic defects include cardiac myosin genes on chromosome 14. Complications of hypertrophic cardiomyopathy include:

• atrial fibrillation
• atrial thrombus and systemic embolism
• infective endocarditis of the mitral valve
• cardiac failure
• sudden death.

Dilated cardiomyopathy

Dilated cardiomyopathy is characterised by dilatation of all four cardiac chambers with progressive cardiac failure. The heart is typically enlarged (two to three times normal weight) and flabby at autopsy. Mural thrombi may be present. The microscopic findings are not specific, but there is often patchy ventricular fibrosis. Cardiomyopathy caused by alcohol, chemotherapy agents and haemochromatosis is of the dilated type.

Restrictive cardiomyopathy

Restrictive cardiomyopathy describes a condition of ‘stiff’ ventricles, which fail to relax, impeding diastolic filling. The ventricles are of normal size but the atria are dilated. Microscopically there is non-specific myocardial scarring. Causes include radiation fibrosis and cardiac involvement by amyloid.

Myocarditis

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

• acute cardiac failure
• sudden death
• chronic cardiac failure (usually due to dilated cardiomyopathy).
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.
Box 20

Infection:

• Viral (Coxsackie, ECHO)
• Bacterial (meningococcus)
• Fungal (Candida)
• Parasitic (Chagas’ disease, toxoplasmosis)
Immune-mediated:

• Post-infective (including rheumatic fever)
• Systemic lupus erythematosus
• Transplant rejection
Idiopathic:

• Sarcoidosis

14.3. Congenital heart disease

Learning objectives
You should:

• know the commonest types of congenital heart disease and the aetiological factors that may cause congenital cardiac defects
• understand what is meant by cyanotic congenital heart defects.
Congenital heart disease describes abnormalities of the heart and major vessels that are present at birth. The incidence of congenital heart disease in liveborn infants is approximately 1 : 200. The common lesions include:

• isolated defects in cardiac chamber walls – atrial septal defect, ventricular septal defect
• persistence of embryonic structures – patent foramen ovale, patent ductus arteriosus
• stenosing lesions (‘narrowings’) – aortic valve stenosis, pulmonary stenosis, coarctation of the aorta
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