Circulatory system

The segment of left ventricular wall illustrated above is composed almost entirely of cardiac muscle. As indicated, the thickness of the myocardium differs in the different chambers of the heart, reflecting differences in their functional requirements. Myocardial thickness also differs between individuals, both in health and in various disease states.

Hypertrophy of the heart muscle may occur due to the effects of long-standing physical exertion and training, as in athletes, or it may occur in pathological states. High blood pressure ( hypertension ) leads to the heart muscle pumping against increased resistance and this commonly causes marked thickening of the left ventricular wall. Less commonly but importantly, there are inherited forms of cardiac hypertrophy such as hypertrophic cardiomyopathy . This disorder is an important cause of sudden unexpected cardiac death, especially in young athletes.

Myocarditis is an uncommon inflammatory disorder affecting the cardiac muscle. Its causes are diverse, but viral forms are the most frequent. The diagnosis requires the combination of interstitial inflammation (inflammation between myocytes) and myocyte damage (known as the Dallas criteria ). Myocarditis can be classified by the predominance of inflammatory cells seen on microscopy. A lymphocytic myocarditis is the typical pattern seen in viral myocarditis . An eosinophilic myocarditis can be seen in the setting of hypersensitivity. Other rarer types of myocarditis include giant cell myocarditis. Sarcoidosis, a systemic granulomatous condition, is a cause of granulomatous myocarditis.

A adipose tissue C capillary CA coronary artery E endocardium F fibrocollagenous pericardium ID intercalated disc M myocardium P pericardium PM papillary muscle

A aorta BB bundle branch E endothelial cell En endocardium F fibrous connective tissue IVC inferior vena cava LA left atrium LF lamina fibrosa LV left ventricle M cardiac myocytes P Purkinje fibre PA pulmonary artery RA right atrium RV right ventricle SVC superior vena cava VR valve ring

The myocardial cells have a high energy demand and therefore a high and constant oxygen requirement. When there is a reduction of blood flow to the myocardium caused by atherosclerosis of the epicardial coronary arteries , the cardiac myocytes supplied by the artery can die ( necrosis ). The patient develops angina (a characteristic crushing central chest pain on exertion, disappearing on rest). With increasingly severe ischaemia of the myocardium, the angina symptoms appear with minimal or no exertion.

Histologically, the dead muscle fibres are replaced by collagenous fibrous tissue ( replacement fibrosis ) and remaining muscle fibres enlarge and increase their work rate ( hypertrophy ) to compensate.

When a coronary artery suddenly becomes completely occluded (e.g. by thrombosis ), a substantial mass of the heart muscle cells dies. For example, the muscle comprising the entire anterior wall of the left ventricle and the anterior part of the interventricular septum dies if the left anterior descending coronary artery is blocked. This is called myocardial infarction , commonly referred to as a ‘heart attack’. Death of some of the conducting bundles of Purkinje fibres can also lead to potentially fatal abnormalities of cardiac rhythm ( arrhythmia ). When the area of infarction heals, the large areas of replacement fibrosis are strong but not contractile, so the patient may suffer from persistent left heart failure as the heart cannot adequately pump blood from the left ventricle to the systemic circulation.

The aortic valve normally has three cusps, but occasionally there are only two (bicuspid) due to a developmental anomaly. Bicuspid aortic valves are particularly prone to develop fibrous thickening, within which calcium salts are deposited to make fibrocalcific nodules. These severely distort the cusps, which also tend to fuse. This disease, called calcific aortic valve disease , interferes with valve function, reducing flow of blood through the valve during systole ( aortic stenosis ) and allowing blood to leak back from the aorta into the left ventricle during diastole ( aortic regurgitation ).

Thrombosis may occur on the free edges of heart valves and, if there is subsequent bacteraemia , they may become infected ( valvitis or endocarditis ). Depending on the bacterium involved, the infected thrombus may erode the valve, leading to severe valve failure, or fragments of the thrombus may break off and pass in the circulation to distant sites where they may block arteries ( embolism ).

Elastic and muscular arteries develop atherosclerosis in which lipid material infiltrates the tunica intima and accumulates in macrophages. This stimulates the proliferation of intimal fibroblasts and myointimal cells, with collagen deposition to produce a plaque which thickens the intima. If severe and in a small-diameter artery, this intimal thickening can severely reduce the artery lumen and limit the blood flow. These plaques commonly rupture, leading to aggregation of platelets and fibrin. This forms a thrombus which narrows the vessel lumen leading to infarction.

A further consequence of severe atheroma in elastic arteries is that the muscle cells in the tunica media are replaced by non-contractile and non-elastic collagen, leading to a weakness in the artery wall, which may bulge and rupture ( aneurysm ).

A tunica adventitia EEL external elastic lamina EL elastic lamina I tunica intima IEL internal elastic lamina LF lamina fibrosa M tunica media VV vasa vasorum

An aneurysm is an abnormal and permanent dilatation of the wall of an artery. Various types of aneurysm can occur, and these can be classified in several different ways: according to morphology (shape) into saccular and fusiform types, according to aetiology (cause) into congenital, acquired, atherosclerotic, mycotic, etc., or by the nature of the aneurysmal wall into true or false aneurysms. The wall of a true aneurysm includes all of the normal layers of the vessel wall, whilst a false aneurysm is deficient in one or more of these layers and essentially represents a protrusion at a site of weakness or deficiency in the vessel wall.

Atherosclerotic aneurysms are common in developed cultures and most often affect the abdominal aorta . These aneurysms are acquired and are usually fusiform in shape.

Rupture of such aneurysms can occur when the wall becomes attenuated due to increasing dilatation. Catastrophic and rapidly fatal haemorrhage can occur unless immediate treatment is available. If such aneurysms are identified before acute presentation with haemorrhage, planned operative repair can be performed. This approach dramatically reduces morbidity and mortality when compared against attempted repair after bleeding has occurred. Some patients can be treated by minimally invasive radiological techniques instead of open surgery.

An aortic dissection can be caused by weakening of the aortic wall due to longstanding hypertension or inherited connective tissue disease affecting the aorta, such as Marfan syndrome.

A tunica adventitia At arteriole BM basement membrane BMp pericyte basement membrane C capillary E endothelial cell F collagen fibrils IEL internal elastic lamina M tunica media Ma metarteriole MF marginal fold P pericyte S arteriovenous shunt SM smooth muscle cell V venule

BM basement membrane D diaphragm EC endothelial cell cytoplasm F fenestration MF marginal fold Ps pseudopodium V pinocytotic vesicle WP Weibel–Palade body

• Act as a permeability barrier

• Synthesise collagen and proteoglycans for basement membrane maintenance

• Synthesise and secrete molecules which minimise pathological thrombus formation e.g. prostacyclin, thrombomodulin, nitric oxide (which inhibits platelet adhesion and aggregation)

When damaged, endothelial cells:

• Secrete vasoactive factors controlling blood flow e.g. nitric oxide, prostacyclin and vasoactive peptides such as endothelin

• Synthesise and secrete molecules which promote protective thrombus formation e.g. von Willebrand factor (factor VIII)

A arteriole Ad adventitia C capillary CV collecting venule L valve leaflet M media MV muscular venule PCV postcapillary venule V venule