Atherosclerosis and arteriolosclerosis

ATHEROSCLEROSIS AND ARTERIOLOSCLEROSIS. HYPERTONIC DISEASE AND SYMPTOMATIC HYPERTONIAS. ISCEMIC HARD DISEASES. CEREBROVASCULAR DISEASES.

 

Cardiovascular diseases are common and important causes of morbidity and mortality worldwide, particularly in industrialized countries. In spite of significant advances in primary prevention and therapy, cardiovascular disease, primarily the complications of atherosclerosis and hypertension (HTN), is still the leading cause of mortality in the United States.

CONGENITAL HEART DISEASE

Congenital malformations of the heart and major blood vessels are produced during embryologic development of the cardiovascular system in the early fetus. They usually arise from randomly occurring defects in embryogenesis, but they sometimes develop as a result of intrauterine infections, such as rubella, or as components of genetic abnormalities such as trisomy 21 (Down syndrome) or cytogenetic disorders of sex chromosomes (Turner syndrome). The 3 major pathophysio-logic categories of congenital heart disease are those causing a left-to-right shunt of blood across the circulation (e.g., ventricular septal defect [VSD], atrial septal defect fASDJ, patent ductus arteriosus [PDA]), a right-to-left shunt (e.g., tetralogy of Fallot), and obstruction without a shunt (e.g., coarctation of the aorta).

ATHEROSCLEROTIC DISEASES

         Atherosclerosis is a chronic disease due to breach of fatty and albuminous substances exchange/metabolism. On determination of WHO, atherosclerosis is “various combinations of changes of internal membrane of arteries, which shows up as a focus laying of lipids, difficult connections of carbohydrates, elements of blood and circulatory in it matters, the formation of the connecting tissue and laying of calcium”. Atherosclerosis damages vessels of elastic and elastic-muscular types. According to prevalence, it  occupies the first place in cardio-vascular pathology. Recent epideMyological data reveals a high occurrence in highly developed countries. It occurs mainly in people of mature age – after 30-35.

Etiology. It is a polyetiologic disease. There are a number of risk factors which are instrumental in the increase of the level of atherogenic lipoproteins  in blood and their penetration into the walls of vessels: arterial hypertension, diabetes mellitus, obesity, hypodynamia, smoking, hyperlipidemia and dyslipoproteinemia, inherited inclination, age, sex (more frequently occurs in men), psychoemotional overstrain, etc.

There are some theories of the development of atherosclerosis : the infiltrative theory of Anichkov,  the nervous metabolic theory of Myasnikov, the immunological theory of Klimov and Nagornev, the viral theory, the gerontology theory of Davidovskiy, the thrombogenic theory of Rokitansky.

Pathogenesis. The pathogenetic essence of atherosclerosis consists of the formation of lesions of atherogenic lipoproteins  in the intimae of arteries of in response to the damage of the endothelium.

         Lipoproteins  are spherical particles which consist of a core and an external membrane. In the complement of core are triglycerides and esters of cholesterol, in the complement of external membrane are protein (apoproteins), phospholipids and unesterified cholesterol. Four classes of lipoproteins  circulate in blood, which differ in sizes and maintenance of cholesterol and albumens – chylomicrons, lipoproteins  of very low and high density. Atherogenic are considered to be lipoproteins   of very low and low density, which contain the large supply of cholesterol (to 45%) and little apoprotein. Lipoproteins  of high density in contrast, have much apoprotein (55%) and comparatively little cholesterol (16%). They execute an antiatherogenic function, that prevents the development of atherosclerosis.

Pathological anatomy. In the development of atherosclerosis four stages are distinguished –the prelipid  stage, the stage of lipid spots, the stage of fibrous plaques(atheroma) and the stage of the complicated defeats (ulceration, calcinosis, thrombosis).

         The prelipid stage is characterized by such processes, as the loss of glycocalix – protective polysaccharide layer of endotheliocytes, the expansion of intraendothelial cracks, the activation of endocytosis in endothelial cells. Intima swells up. In the subendothelial space, lipoproteins  begin to penetrate from plasma of blood in increasing amounts.

The main transport form of cholesterol is lipoproteins  of low density. They transport cholesterol from liver to the cells of organism. The mechanism by which cholesterol is transported into the cell, which is receptor-mediated, is called endocytosis. Parenchymatous cells and connective tissue types (fibroblasts, fibres of smooth muscles of arteries) capable of binding lipoproteins  of low density have specific receptorson their surfaces(apo-v, Å-receptors). This co-operation takes place in the area of the special diaphragm structures, adopted by the coated pits. After co-operating with the particles of the lipoprotein the coated pits invaginate and fuse, forming bordered endocytic vesicle. They contact with lysosomes and fuse. The released cholesterol is utilized for the necessities of the cell, for example for the synthesis of membranes and hormones. Receptor-mediated endocytosis is regulated by the mechanism of feed-back. At the increase of cholesterol the quantity of Apo-v diminishes in a cell, Å-receptors on its membrane, and fusion of lipoproteins is limited. That is why there is no transport of cholesterol by receptormediated way to its accumulation in the cytoplasm.

 

 

 

It has been lately proved that in the genesis of atherosclerosis a leading role is played not by native lipoproteins   of low density, but by their modified variants. Name such change of structure of Lipoprotein particle modification, when it stops to be recognized Apo-v, by the Å-receptors of fibroblasts and other cells and is not taken in by them. The modification of lipoproteins   takes place in blood and vascular wall. To the major modified forms belong:

à) glycosylated lipoproteins  , to which glucose was added;

b) peroxide-modified lipoproteins, which appeared under action of free radicals and products of peroxide oxidization of lipids;

c) autoimmune complexes of lipoproteins   antibodies;

d) lipoproteins  , that were partially degraded bt the action of proteolytic enzymes.

Modified lipoproteins, which entered the subendothelial space from blood or appeared in a vascular wall, carry with them macrophages. On the surface of these cells, next to typical Apo-B and E-receptors, are located receptors to the other type, adopted phagocytes -receptors. phagocytosis – absorption of modified lipoproteins   greatly differs from endocytosis of native lipoproteins  , mediated through Apo-B and E-receptors. This mechanism is not regulated by the principle of feed-back regulation that is why a high amount of lipoproteins   of low density rich in cholesterol penetrates the Macrophages uncontrollably. The activity of lyzosomal enzymes becomes insufficient for the breaking up of the esters, and gradually the cytoplasm of macrophages becomes overfilled with lipid vacuoles with the accumulated esters of cholesterol. Under a microscope it looks like dots, that is why such cells are called foamy cells. The transformation of macrophaes to foamy cells is the irreversible stage of atherosclerotic process.

High density lipoproteins counteract the convertion of macrophages into foamy cells. They easily penetrate through the intimae, saturated cholesterol and likewise easily go back the into blood.  Macrophages have on their surfaces, specific receptors for  high density lipoproteins. The particles of lipoproteins   after binding to the receptors are taken in, but are not broken by the enzymes of lysosomes. Enriched in cholesterol, they leave the macrophages by the mechanism of exocytosis and migrate to a blood-stream. Removal of cholesterol by this mechanism is important for those cells which take in modified lipoproteins   through apo-B,E-receptors, that are uncontrolled. Purging them of surplus cholesterol, high density lipoproteinsslow development of atherosclerosis by such method.

         Another characteristic morphological feature of atherogenesis is the proliferation of the cells of smooth muscles in the intimae of vessels. Myocytes migrate here from the middle layer of arteries (media) under action of factors of chemotaxis, and their reproduction depends on the growth factors – thrombocytic, fibroblastic, endothelial. The myocytes which migrated to the intima and began to propagate themselves transform from retractive cells into metabolically active ones. Without regard to the absence of scavenger -receptors, they acquire the property to take in modified lipoproteins   and accumulate esters of cholesterol. Foamy cells also appear from them.

         Lipid spots (strips) appear in different parts of the arterial system, but firstly, in the aorta. From cellular elements, foamy cells, T-lymphocytes and fibres of smooth muscles, prevail in them. In this stage, esters of cholesterol are mainly in cells. Around, there is insignificant excrescence of the connective tissue. Lipid spots do not hinder blood stream.

       Foamy cells, overloaded with cholesterol, collapse in the course of time, and cholesterol is poured into the extracellular space. It irritates the surrounding tissues as an extraneous body and causes brief cellular proliferation at first, and afterwards – progresses to fibrosis. The accumulations of foamy cells and extra cellular lipids, embedded between elastic fibres, make light intima. Glycosaminglycans are replaced in it by γ-globulin and fibrin.

      The fibres of smooth muscles which migrated into the intima from the media grow into secretory cells. They begin to increase the production of connective tissue proteins – elastin, collagen. Fibrotic tissue which surrounds lipid corpuscles like a capsule is formed from them. This structure is called the fibrous plaque. It is dense macroscopically, oval, white or whitish yellow color, and rises above the surface of the intimae. That part which bulges into the lumen of the vessel, is denser and that is why it obstructs the blood stream.

       Fibrous plaques consist of amorphous mass, which tailings of elastic and collagen fibres, cholesterol, enter in the complement foamy cells are not blasted. If the processes of disintegration of plaques prevail over the formation of necrotic masses, then such plaques are called atheromatos. Foamy cells, lymphocytes, plasmocytes, newly formed vessels, accumulate on the periphery of the plaque. The lumen of the vessel   is marked off *hyalinised* by the connective tissue (overlay of plaque). Complications begin on this stage.

      Parietal blood clots often appear in the area of fibrous plaques. Their appearance is study theed by the ruptures of fibrous capsule of plaques, and also by the demage of the endothelium under them.

      Ulceration of plaques – is also a frequent phenomenon. An ulcer has unequal edges, its bottom is formed by muscular layer or advevtitia. The defects of plaques are often covered by blood clots. If atheromatous masses get into the blood stream, they become the cause of brain embolism and embolism of other organs.

      Another complication of fibrous plaques –is calcification (atherocalcinosis). This process is complete with atherosclerosis. Salts of lime are put aside in atheromatous masses, the fibrous tissue and intermediate matter between elastic fibres. Plaques attain stony consistency. The focus of calcinosis is localized mainly in abdominal aorta, coronary arteries and arteries of pelvis and thighs.

 

 

Rupture of aortic aneurysm

 

     Depending on the localization of atherosclerosis, the following clinical-morphological forms can be distinguished: atherosclerosis of the aorta, atherosclerosis of the coronary vessels, atherosclerosis of arteries of the cerebrum, atherosclerosis of arteries of the kidneys, atherosclerosis of arteries of the intestine, atherosclerosis of arteries of the lower limbs.

 

• Affects large and medium-sized arteries

• Lesions comprise fatty streaks, fibrolipid plaques and complicated lesions

• Risk factors include increasing age, male gender, hypertension, smoking and diabetes

• Associated with increased levels of LDL-cholesterol, Lp(a), fibrinogen and factor VII and reduced levels of HDL-cholesterol

Atherosclerosis, or atheroma, is the term used to describe a disease of large and medium-sized arteries, characterised by fibrosis, lipid deposition and chronic inflammation. Its frequency has increased dramatically during the past 50 years. In some countries, notably the United States, the incidence of the disease appears to have peaked and, indeed, is now declining. However, in some European countries and in parts of the Middle and Far East the incidence of atherosclerosis is increasing. Because atheroma causes narrowing or obstruction of many different arteries, a wide range of clinical disorders result. Atheroma of the coronary arteries, ‘coronary heart disease’, is one of the commonest causes of death in many societies. Major cause of organ ischaemia (e.g. myocardial infarction).

It is a disease of the lining and the wall of large and medium-sized arteries. It is most uncommon in vessels smaller than 2-3 mm in diameter. The disease progresses from inconsequential lesions of the intimal lining to large and friable ‘plaques’ that can rupture, thrombose or fragment. In the early stages there are individual lesions but in the late stages the disease can become confluent

The earliest significant lesion is called a fatty streak. It is a yellow linear elevation of the intimal lining and is composed of masses of lipid-laden macrophages. It occurs in all population groups and in both genders. These fatty streaks have no clinical significance. They are only important because in patients at risk they progress to more serious lesions, which have been called fibrolipid plaques and complicated lesions. These have a tendency to form close to branches and have a core of lipid with a cap of fibrous tissue. They have recently been renamed fibrous cap atheromas. If the fibrous cap is thin and inflamed it may rupture and become thrombosed. If the thrombus is large the artery may become obstructed. Smaller thrombi may become organised. Repeated episodes of rupture, thrombosis and repair contribute to the enlargement of atheromatous plaques.

Causes atheroma

This is not known. One of the most puzzling features of atherosclerosis is the wide variation in the severity and distribution of lesions between individuals, even within the same population groups. Many factors increase the risk of an individual developing severe or premature atheroma, but some patients who present with clinical disease have no obvious risk factors. The incidence of atherosclerosis increases with age. Significant disease in females is unusual before the menopause. Hypertension, hyperlipidaemia and diabetes are important risk factors in both genders, while cigarette smoking is of more significance in younger males. Other risk factors include obesity, a sedentary lifestyle, low socio-economic status and low birth weight

Despite the development of many imaging techniques, it is difficult to follow the progression of atherosclerosis in individual patients. For this reason, much of the information on the evolution of atheromatous plaques comes from carefully designed postmortem studies of patients of different ages and racial origin and from studies in animals which develop atherosclerosis either spontaneously or following high-fat or cholesterol-supplemented.

 Electron microscopy has demonstrated a variety of changes in the early stages of disease. In sites predisposed to atherosclerosis, macrophages can be seen entering and leaving the arterial wall between endothelial cells. The molecular mechanisms which allow macrophages to adhere to the endothelium are similar to those that occur in acute inflammation but are not as clearly understood. Endothelial cells overlying atheromatous plaques show enhanced expression of some cell adhesion molecules, including ICAM-1 and E-selectin. This may be one mechanism by which inflammatory cells accumulate in plaques. A more advanced atheromatous plaque contains a mixture of macrophages, T-lymphocytes and smooth muscle cells, and is usually capped by a layer of fibrous tissue. Growth factors, particularly platelet-derived growth factor (PDGF), stimulate the proliferation of intimal smooth muscle cells (myointimal cells) and their subsequent synthesis of collagen, elastin and mucopolysaccharide. Growth factors, such as PDGF, are secreted by a large number of cells of connective tissue origin, by macrophages and by endothelium.

Lipids important in atherosclerosis.

The increased risk of coronary heart disease in the United Kingdom and many other Northern European countries has been associated with diets high in saturated fat. In Mediterranean communities, a much lower proportion of energy is obtained from saturated fat, and coronary heart disease death rates are much lower. Lipids, such as cholesterol and triglycerides, are poorly soluble and are transported in the blood as lipoproteins. The protein components of lipoproteins are termed apolipoproteins. Many epidemiological studies have shown that increased plasma level of low-density lipoprotein (LDL)-cholesterol or reduced levels of high-density lipoprotein predispose to atherosclerosis. The most compelling evidence of the importance of LDL-cholesterol comes from studies of patients and animals who have a genetically determined lack of cell membrane receptors for LDL. About 1 in 500 Caucasians are heterozygous for this type of mutation, have reduced numbers of functional receptors on their cell surfaces and elevated plasma LDL-cholesterol levels (over 8 mmol/l). They often develop coronary heart disease in their forties or fifties. The rare patients who are homozygous for one of these mutations (approximately 1 per million) have much greater cholesterol levels and usually die from coronary atheroma in infancy or the teens. 

Microscopic (a- d) . Atherosclerosis of the coronary arteries of the heart: a, – unstable atherosclerotic plaque (a large lipid core with necrosis , thinning and rupture of fibrous cap ), b – lipids in the tire patches , g – head of a blood clot in the tire plaque rupture .

There is a complex, and incompletely understood, pattern of lipid transport from the gastrointestinal tract to the liver and the peripheral tissues. Lipid passes from the bloodstream into and out of the arterial wall. It accumulates preferentially in atheromatous lesions and may aggregate into a large pool, called a lipid core. Lipid that becomes oxidised is preferentially taken up (‘scavenged’) by macrophages, which develop a characteristic foamy appearance.

Macropreparations (a-f). Atherosclerosis of the coronary arteries of the heart: the unstable atherosclerotic plaque: a – with atheromatous occlusion of the masses, b – with occlusive thrombus, c, d – with severe atheromatosis, e, f – with hemorrhage into the plaque, g – occlusive thrombus in a longitudinally sectioned coronary artery disease).

Inflammation, infection and disordered immunity in atherosclerosis

There is no doubt that inflammation and disordered immunity are important in the development of atheroma but there is as yet no proof that a particular organism is a specific cause of atheroma. The evidence includes the following:

• Most atheromatous plaques contain inflammatory cells, including macrophages and T-lymphocytes.

• A variety of cytokine molecules and growth factors have been identified in lesions. These include pro-inflammatory cytokines such as interleukins IL-1 and IL-6 and proteins that are chemotactic for macrophages.

• In patients with coronary heart disease, elevated levels of inflammatory markers, such as C-reactive protein, are associated with an increased risk of further acute events.

• Patients with clinical evidence of atheroma have elevated levels of antibodies to micro-organisms such as Chlamydia pneumoniae. Various other micro-organisms, including herpes viruses, cytomegalovirus and Helicobacter, have been implicated as a cause of atherosclerosis. The evidence that they have a causative role is limited.

• Patients who have received cardiac transplants may develop an accelerated form of coronary heart disease in the transplanted heart. There are subtle histological differences between the usual form of atheroma and so called ‘transplant atherosclerosis’. Nevertheless, the occurrence of this form of disease further supports the concept that atheroma is a disease of disordered immunity. To minimise post-transplant atherosclerosis, patients who have received a cardiac graft are treated with lipid-lowering agents.

Other aspects of the pathogenesis of atherosclerosis

Fetal origin of adult diseases

Recent epidemiological studies have shown that there is a strong relationship between environmental influences in early life and the later development of common disorders, including coronary heart disease and hypertension. Barker and his colleagues saw a striking similarity between a map of death rates from coronary heart disease in England and Wales between 1968 and 1978 and a map of infant mortality between 1907 and 1910. They realised that areas where babies had been least healthy at the beginning of the century were showing up as ‘hot spots’ for coronary heart disease many years later. Subsequent studies, notably in Hertfordshire, Sheffield and India, have confirmed the fetal origin of adult disease hypothesis. For example, men who weighed 18 pounds or less at 1 year were 2-3 times more likely to die of coronary heart disease than men who had weighed 26 pounds or more. In particular, subjects with a low birth weight, or a low weight in infancy, who become overweight subsequently, are at particular risk of developing coronary heart disease or diabetes in later life. The role of early life events in the origin of many different diseases, including diabetes and osteoporosis, is under intensive study. The relationship between low birth weight and later development of hypertension has been confirmed in experimental models and may lead to an understanding of the underlying mechanisms.

Coagulation factors

Histological studies of atheromatous lesions in both humans and animals have shown that fibrin and platelets are important constituents of early lesions. Any change that predisposes to platelet aggregation and blood coagulation would have important influences on the formation of atheromatous lesions and the development of acute coronary syndromes such as unstable angina and acute myocardial infarction. There is now strong evidence that increased levels of blood coagulation factor VII are associated with an increased risk of ischaemic heart disease.

Macropreparations (a- c) . Atherosclerosis of the aorta with parietal thrombus : aortic intima with marked changes – lipid (yellow) spots, fibrous ( atherosclerotic ) plaques, towering above the surface of the intima – a dense consistency , yellowish -white, visible lesions complicated – multiple ulceration of atherosclerotic plaque , mural thrombi with a characteristic corrugated surface.

Monoclonal origin of atheromatous lesions

Early atheromatous lesions are derived from a monoclonal proliferation of smooth muscle cells. This suggests that a single cell, or clone of cells, may have been induced to grow by a protein which stimulates abnormal and uncontrolled proliferation (a ‘mutagen’). In this way, atheromatous lesions have been likened to small benign tumours. Although this is an attractive theory, no growth factor, proto-oncogene or exogenous mutagen has been identified that might act in this way.

ANEURYSMS

• Localised, permanent, abnormal dilatation of a blood vessel

• Atherosclerotic. Usually occur in the abdominal aorta; rupture causes retroperitoneal haemorrhage

• Dissecting. Usually occur in the thoracic aorta; dissection along the media causes vascular occlusion and haemopericardium

• Berry. Occur in the circle of Willis; rupture causes subarachnoid haemorrhage

• Capillary micro-aneurysms. May be intracerebral (in hypertension), causing cerebral haemorrhage, or retinal (in diabetes), causing diabetic retinopathy

• Syphilitic. Usually occur in the thoracic area

• Mycotic. Rather rare; commonest in the cerbral arteries

An aneurysm is a localised permanent dilatation of part of the vascular tree. Permanent dilatation implies that the vessel wall has been weakened. In contrast, a false aneurysm is a blood-filled space that forms around a blood vessel, usually after traumatic rupture or a perforating injury. A haematoma forms and is contained by the adventitial fibrous tissue. A common cause of false aneurysm formation is femoral artery puncture during arteriography or percutaneous angioplasty.

Atherosclerotic abdominal aortic aneurysms commonly develop in elderly patients. They can be detected by ultrasound examination and the value of screening for these aneurysms is under study. They may impair blood flow to the lower limbs and contribute to the development of peripheral vascular disease. Most importantly, they may rupture into the retroperitoneal space. Elective repair of these aneurysms is comparatively safe but repair after rupture has a high mortality. Some are now managed by percutaneous insertion of supportive stents and this form of treatment may become more common in the future. Aneurysms of the proximal and thoracic aorta are much less common. As with abdominal aneurysms, atherosclerosis is the commonest cause. In atherosclerotic aneurysms there is usually a pronounced loss of elastic tissue and fibrosis of the media. This is due to ischaemia of the aortic media, and release of macrophage enzymes causing fragmentation of elastic fibres. There is evidence that some aortic aneurysms are familial, and inherited defects in collagen have been postulated as the underlying cause.

Aortic dissection (dissecting aneurysms)

In aortic dissection, blood is forced through a tear in the aortic intima to create a blood-filled space in the aortic media. This can track back into the pericardial cavity, causing a fatal haemopericardium, or can rupture through the aortic adventitia. In occasional cases the track re-enters the main lumen to create a ‘double-barrelled’ aorta. The intimal tear and the anatomical features of the aorta can be demonstrated in life by CT or MRI scanning. The underlying pathology is poorly understood. In some, but by no means all, cases but there is pronounced degeneration of the aortic media. This is the so-called cystic medial necrosis and is characterised by mucoid degeneration and elastic fibre fragmentation. An exaggerated form of this change is seen in Marfan’s syndrome, a congenital disorder of the expression of a glycoprotein, fibrillin, closely associated with elastin fibres. The strongest risk factor for dissecting aneurysm is systemic hypertension. In some cases the intimal ‘entry’ tears are around atheromatous plaques, but in most cases they involve disease-free parts of the aorta. Without treatment, the mortality from dissecting aneurysm is at least 50% at 48 hours, and 90% within 1 week. The immediate aim of treatment is to contain the propagating haematoma by reducing arterial pressure. Surgical repair is feasible in some patients, especially if the process affects the proximal aorta.

HYPERTENSION

• Classified aetiologically into essential (primary) hypertension, in which there is no evident cause, and secondary hypertension

• Secondary hypertension may be due to renal disease, adrenal cortical and medullary tumours, aortic coarctation or steroid therapy

• Further classified dynamically into benign hypertension, in which there is gradual organ damage, and malignant hypertension, in which there is severe and often acute renal, retinal and cerebral damage

Definition

Hypertension is the commonest cause of cardiac failure in many societies and a major risk factor for atherosclerosis. Furthermore, it is a major risk factor for cerebral haemorrhage, another leading cause of death worldwide. There is no universally agreed definition of hypertension, but most authorities would accept that a sustained resting blood pressure of more than 160/95 mmHg is definite hypertension. Furthermore, this would be categorised as:

• mild when the diastolic pressure is between 95 and 104 mmHg

• moderate at 105-114 mmHg

• severe at pressure above 115 mmHg.

Aetiological classification

Hypertension can be classified aetiologically according to whether the cause is unknown-essential (primary or idiopathic) hypertension-or is known-secondary hypertension. Most cases of hypertension are classified as ‘essential’, but the possibility of an underlying cause should always be considered.

Essential (primary) hypertension Unknown, but probably multifactorial involving:

• Genetic susceptibility

• Excessive sympathetic nervous system activity

• Abnormalities of Na/K membrane transport

• High salt intake

• Abnormalities in renin-angiotensin-aldosterone system

Secondary hypertension:

• Chronic renal failure

• Renal artery stenosis

• Glomerulonephritis Endocrine causes

• Adrenal tumours (cortical or medullary)

• Cushing’s syndrome Coarctation of aorta

Drugs, e.g. corticosteroids, oral contraceptives

Essential hypertension.

Up to 90% of patients who present with elevated blood pressure will have no obvious cause for their hypertension and are therefore said to have essential or primary hypertension

Detailed clinical and physiological investigations in patients with essential hypertension indicate that it is not a single entity, and that several different mechanisms may be responsible. The key feature in all patients with established hypertension is an increase in total peripheral vascular resistance. The pathophysiological mechanisms currently under scrutiny involve:

 

• sodium homeostasis and salt sensitivity

• the sympathetic nervous system

• the renin-angiotensin-aldosterone system.

Sodium homeostasis

Some experts consider that salt intake is an important factor in hypertension but others disagree with this viewpoint. However, there is a general concern about the levels of dietary salt, especially in preprepared food dishes. Impaired renal sodium excretion may be one of the first changes in the development of hypertension. Sodium retention is followed by an expansion of blood volume and a subsequent increase in cardiac output. Peripheral autoregulation increases peripheral vascular resistance and eventually leads to hypertension. In patients with essential hypertension, sodium-potassium transport in both red and white cells is abnormal. Total body sodium levels are positively correlated with blood pressure in some hypertensive patients, but not iormotensive controls.

The sympathetic nervous system

Blood pressure is a function of total peripheral resistance and cardiac output; both of these are, to some extent, under the control of the sympathetic nervous system. When compared with controls, patients with essential hypertension have higher blood pressures at any given level of circulating plasma catecholamines, suggesting an underlying hypersensitivity to these agents. The circulating levels of catecholamines are highly variable and can be influenced by age, sodium intake, posture, stress and exercise. Nevertheless, young hypertensives tend to have higher resting plasma noradrenaline levels than age-matched, normotensive controls.

The renin-angiotensin-aldosterone system

Renin is released from the juxtaglomerular apparatus of the kidney, diffusing into the blood via the efferent arterioles. It then acts on a plasma globulin, variously called ‘renin substrate’ or angiotensinogen, to release angiotensin I. This is in turn converted to angiotensin II by angiotensin converting enzyme (ACE). Angiotensin II is a powerful vasoconstrictor and is therefore capable of inducing hypertension. However, only a small proportion of patients with essential hypertension have raised plasma renin levels, and there is no simple correlation between plasma renin activity and the pathogenesis of hypertension. There is some evidence that angiotensin can stimulate the sympathetic nervous system centrally, and many patients with essential hypertension respond to treatment with ACE inhibitors.

Pathological classification

Hypertension is classified also according to the clinicopathological consequences of the blood pressure elevation. Benign or essential hypertension is often asymptomatic and discovered only during a routine medical examination. Malignant hypertension is a serious conditioecessitating prompt treatment to minimise organ damage or the risk of sudden death from cerebral haemorrhage.

Benign (essential) hypertension

 The increased peripheral vascular resistance and cardiac workload associated with hypertension produce left ventricular hypertrophy. During life this can be detected electrocardiographically, and at postmortem there is often substantial, concentric thickening of the left ventricle. With the development of congestive cardiac failure, the hypertrophy can be obscured by left ventricular dilatation. Some patients with hypertension also have coronary arterial atherosclerosis and evidence of consequent ischaemic heart disease.

Longstanding hypertension produces generalised disease of arterioles and small arteries , in addition to enhancing the development of atherosclerosis. The changes are most easily appreciated in the retina during life, and in the kidneys at autopsy. Medium-sized renal arteries and renal arterioles show marked intimal proliferation and hyalinisation of the muscular media. This produces focal areas of ischaemia with scarring, loss of tubules and periglomerular fibrosis. The cortical surfaces are finely granular.

Malignant hypertension

Malignant hypertension is a clinical and pathological syndrome. The characteristic features are a markedly raised diastolic blood pressure, usually over 130-140 mmHg, and progressive renal disease. Renal vascular changes are prominent, and there is usually evidence of acute haemorrhage and papilloedema. Malignant hypertension can occur in previously fit individuals, often black males in their third or fourth decade. However, most cases occur in patients with evidence of previous benign hypertension; this is sometimes termed accelerated hypertension.

The consequences of malignant hypertension are:

• cardiac failure with left ventricular hypertrophy and dilatation

• blurred vision due to papilloedema and retinal haemorrhages

• haematuria and renal failure due to fibrinoid necrosis of glomeruli

• severe headache and cerebral haemorrhage.

The characteristic histological lesion of malignant hypertension is fibrinoid necrosis of small arteries and arterioles . The kidney is frequently affected and some degree of renal dysfunction is inevitable. Occasionally there is massive proteinuria, and renal failure develops. Acute left ventricular failure can occur.

Renal type of hypertension may be benign and malignant. Benigephrosclerosis is the term used to describe the kidney of benign phase of hypertension. Macroscopically, both kidneys are affected equally and are reduced in size and weight, often weighing about 100 gm or less. The capsule is often adherent to tht cortical surface. The surface of the kidney is finely’ granular and shows V-shaped areas of scarring (<<small contracted kidney>>). The cut surface shows firm kidney and narrowed cortex. Microscopically there are primarily difflise vascular changes, which produce parenchymal changes secondarily as a result of ischaemia. Parenchymal changes. There is variable degree of atrophy of parenchyma. These includ glomerular shrinkage, deposition of collagen ir Bowman’s space, periglomerular fibrosis. Clinicaj features is variable: elevation of the blood pressurl with headache, dizziness, palpitation. Renal failure ani uremia may occur.

 

Macropreparations (a- d) . Arteriolosklerotichesky nephrosclerosis : c, d – nefrotsirroz , primary shrunken kidneys. The kidneys are reduced in size, sealed with a fine-grained surface , small cysts with clear content , the cut cortex ( especially) and medulla thinned , increased the amount of fat gate kidney.

 

Microscopic (a, b). Arteriolosklerotichesky nephrosclerosis : 1 – hyalinosis and sclerosis of the arterioles , 2 – hyalinosis of glomeruli ( preserved compensatory enlarged) , 3 – stromal sclerosis , 4 – protein dystrophy and atrophy of the epithelium of the convoluted tubules.

 

CORONARY (ISCHEMIC) HEART DISEASE

• A common cause of cardiac failure

• Usually due to coronary artery atheroma

• Myocardial lesions include ischaemic fibrosis and acute infarction

• Most frequent cause of death in Western societies

Pathophysiology

Under normal conditions, the blood flow in coronary arteries is closely matched to the metabolic demands of cardiac muscle. Ischaemic heart disease results when the blood supply becomes insufficient, because:

• either the blood supply itself is impaired, or

• the myocardium becomes hypertrophic and makes a greater demand on the blood supply.

Coronary blood flow is normally independent of aortic pressure. An efficient autoregulatory mechanism exists to control the blood flow through the coronary vascular bed. When an obstruction develops in a major coronary artery, usually because of atherosclerosis, coronary blood flow is initially preserved, because peripheral resistance distal to the obstruction is reduced. When the vessel lumen is more than 75% occluded, ischaemia develops, particularly if the coronary collateral circulation is poorly developed. Cardiac muscle is extremely active metabolically, and mitochondria constitute over 30% of the volume of individual fibres. Aerobic metabolism is essential, as there are very poor reserves of high-energy phosphates. Cardiac muscle death occurs when tissue adenosine triphosphate (ATP) levels are very low and when anaerobic glycolysis has virtually ceased. As with other tissues, the precise cause of death is uncertain, but lethal cardiac muscle injuries are associated with membrane damage and the sudden entry of calcium into the cell cytoplasm. After brief periods of ischaemia, cardiac blood flow can be re-established. However, after a critical interval ‘reperfusion’ is impossible, probably as a result of swelling of capillary endothelial cells.

The sub-endocardial layers of the myocardium are at particular risk from ischaemia. Even though there is a well-developed sub-endocardial plexus of blood vessels, flow in this part of the myocardium is restricted to diastole. Blood vessels are collapsible tubes and are susceptible to compression when tension within the myocardial wall increases. This tension is greatest when the ventricles are dilated, especially in the sub-endocardial layer.

Atherosclerosis accounts for the vast majority of coronary artery disease and is most marked in the proximal (epicardial) parts of the coronary arteries. The intramural branches may show slight intimal thickening, but are generally free of true atherosclerosis. Ischaemia is produced by:

• progressive atherosclerotic stenosis

• erosion of an atheromatous plaque with superimposed thrombosis

• rupture of the fibrous cap of a plaque with haemorrhage into the lesion and thrombosis.

Some cases of ischaemic heart disease result from atherosclerotic narrowing of the openings (ostia) of coronary arteries. In the past this was usually the result of syphilis, but is now usually atherosclerotic in origin. Occasionally emboli lodge in coronary arteries, usually as a result of infective endocarditis or calcific disease of the aortic valve. Other coronary artery diseases are extremely rare.

Ischaemic heart disease can also result from low coronary arterial perfusion. Shock, especially as a result of haemorrhage, is a frequent cause of this. Severe aortic valve disease, either stenosis or incompetence, can also impair coronary blood flow. Some patients with severe anaemia can develop symptoms of ischaemic heart disease.

Acute myocardial infarction

• Necrosis of heart muscle, usually left ventricular, is usually due to coronary artery atheroma with superimposed thrombus or plaque haemorrhage

• Necrosis is followed by inflammatory infiltration and fibrous repair

• Enzymes released from necrotic muscle into blood, and leukocytosis, are useful diagnostically

• Complications include arrhythmias, cardiac failure, mitral incompetence, myocardial rupture leading to haemopericardium, mural thrombus leading to embolism, and cardiac aneurysm

A myocardial infarct is an area of necrosis of heart muscle resulting from a sudden, absolute or relative, reduction in the coronary blood supply. The commonest precipitating cause is thrombosis superimposed on, or haemorrhage within, an atheromatous plaque in an epicardial coronary artery.

Morphology

The location and size of the infarct depend on:

• the site of the coronary artery occlusion

• the anatomical pattern of blood supply

the presence or absence of an anastomotic circulation within the coronary arterial tree.

The macroscopic and microscopic changes of myocardial infarcts follow a predictable sequence . The chief features are necrosis, inflammatory cell infiltration and, as cardiac muscle cannot regenerate, repair by fibrous tissue. The extensive necrosis of cardiac muscle is associated with the release of cardiac enzymes and proteins into the circulation. A simple bedside test for the diagnosis of acute infarction would allow more rational use of thrombo-lytic drugs. Assays for the blood level of the cardiac muscle protein troponin are the most reliable early biochemical indicator of acute myocardial infarction. Raised serum levels of creatine kinase also suggest acute myocardial infarction but may not be elevated immediately after the infarct. Most patients show a transient leukocytosis in the first 1-3 days, but the value rarely exceeds 15 ×10⁹/l.

Macropreparation (a) . Transmural myocardial infarction: Large ( transmural ) necrotic irregular geometric shapes , colored, form , yellowish- gray in color with red foci , loose consistency, sinks down on the cut , surrounded by a hemorrhagic rim red. Depending on the age of myocardial necrosis may initially be pale red , grayish- yellow , then yellow and greenish- yellow in color ( 1 – necrotic myocardium – myocardial infarction .

Microscopic (a, b). Myocardial infarction ( necrosis stage with the organization ) in the area of ​​necrosis (1 ) cardiomyocytes fragmented, lysed , do not contaiuclei around the area with a full-blooded vascular hemorrhage , leukocyte -macrophage infiltration (zone demarcation inflammation ) of the zone of necrosis in some places grow into young connective ( granulation ) tissue ( 2). Outside the zone of myocardial hypertrophic cardiomyocytes , their nuclei are large, hyperchromatic , sclerotic stroma infarction.

Complications

 

 

 

The underlying pathologic substrate for clinically apparent myocardial ischemia is coronary atherosclerosis in at least 90% of cases. Narrowing of one or more of the coronary arteries to less than 25% of the luminal area can be slowly progressive, giving rise to recurrent episodes of angina pectoris. Acute changes in plaques associated with platelet aggregation and vasospasm can precipitate myocardial ischemia, ventricular fibrillation, and sudden cardiac death. Sudden luminal occlusion due to thrombosis of an ulcerated plaque can give rise to an acute myocardial infarct, usually of the left ventricle (LV), in the distribution of the occluded coronary artery

. Myocardial necrosis begins in the ischemic subendo-cardial myocardium and progresses in a wave-front fashion over a period of 3 or 4 hours to involve the subepicardial myocardium. Myocardial infarcts undergo organization into granulation tissue over approximately 2 to 3 weeks and complete healing as fibrous scars in 2 to 3 months. Larger healed infarcts can develop into ventricular aneurysms. During the first week to 10 days when healing is minimal, myocardial infarcts are susceptible to developing external rupture, giving rise to cardiac tamponade; rupture across the interventri-cular septum, producing a VSD; or rupture of a papillary muscle, giving rise to mitral regurgitation. However, such life-threatening complications occur in only approximately 5% of cases. A massive acute myocardial infarct involving 40% or more of the LV can give rise to fatal cardiogenic s heart failure (CHF) may ensue.

Chronic ischaemic heart disease

Clinical features. Angina is one of the commonest clinical features of patients with a long history of ischaemic heart disease. A history of chest pain, induced by exercise and relieved by rest, should be sought in any patient in whom ischaemic heart disease is suspected. Impaired left ventricular function, following one or more previous episodes of myocardial infarction, may result in left ventricular and, ultimately, congestive cardiac failure. Some patients present with severe or rapidly progressive anginal chest pain. This is termed unstable or crescendo angina. It may progress to myocardial infarction and requires emergency management.

Morphology. Most patients with a definite clinical history of angina have extensive coronary arterial atheroma. Typically, two or three of the major coronary arteries have patches of stenosis in which the lumen is reduced to less than 75% of its normal cross-sectional area. Careful postmortem studies in patients who have died after episodes of unstable angina have demonstrated recent rupture of the fibrous cap of large, often eccentric and lipid-rich atheromatous plaques. Paradoxically some patients with a typical clinical history of angina have relatively normal coronary angiograms. It may be that the recurrent episodes of coronary spasm are responsible for pain in these patients: this is sometimes called ‘variant angina’. Postmortem examinations on patients with a long history of ischaemic heart disease frequently demonstrate areas of healed myocardial infarction, dilatation of the left ventricle, and other changes related to chronic heart failure such as peripheral oedema, pleural and peritoneal effusions, and pulmonary oedema and congestion.

 

Macropreparation (a) . Macrofocal ( myocardial ) cardio : heart increased in size , increased thickness of the wall of the left ventricle – more than 1.2-1.3 cm, increased the amount of trabecular and papillary muscles. The wall of the left ventricle major transmural scar irregular geometric shape , white solid consistency.

Cerebrovascular diseases (cerebral type).

Hypertension can result in two main types of parenchymal diseases of the brain:

1) isehemic brain damage (hypoxic encephaI opathy and cerebral infarction);

2) intracranial hemorrhage (intracerebral and subarachnoid hemorrhage).

The pathologic appearance of the brain in hypoxic encephalopathy varies depending on the duration and severity of hypoxic episode and the length of survival. Macroscopically, there is focal softening. The area supplied by distal branches of the cerebral arteries suffers from the most severe ischemic damage and may develop border zone or watershed infarcts in the adjacent zones between the territories supplied by major arteries. Microscopically, the nerve cells die and disappear and are replaced by reactive fibrillary glia.

Cerebral infarction is a localized area of tissue necrosis caused by local vascular occlusion. Clinically, the signs and symptoms associated with cerebral infarction depend on the region infracted. Cerebral I nfarcts may be anemic or hemorrhagic.

Macroscopically, an anemic infarct becomes evident 6—i 2 hours after its occurrence. The affected area is soft and swollen and there is blurry of junction between grey and white matter. Within 2—3 days, the nfarct undergoes softening and disintegration. A hemorrhagic infarct is red and superficially resembles a hematoma. It is usually the result of fragmentation of occlusive arterial emboli or venous thrombosis. Hemorrhage into the brain of patient with hypertension, is intracerebral hemorrhage, which is usually of hypertensive origin.

Most hypertensives over middle age have microaneurjsm in very small cerebral arteries in the brain tissue. The common sites of hypertensive intracerebral hemorrhage are the region of the basal ganglia, pons and cerebella’s cortex. About 40% of patients die during the first 3—4 days of hemorrhage, mostly from hemorrhage into the ventricles. The outcome of intracerebral hemorrhage is cyst formation.

Macropreparations (a- e). Bleeding in the brain ( non-traumatic intracerebral hematoma) : a- a – intracerebral hematoma ( brain tissue in the lesion is destroyed, in its place – the large blood clots deep red color ) with the breakthrough of blood into the subarachnoid space surrounding the brain tissue swelling (and c) and d , d – subarachnoid hematoma ( liquid blood and blood clots of various sizes in the subarachnoid space.

Microscopic . Bleeding in the brain : blood elements with partially lysed red blood cells to the site of the destroyed nerve tissue , preserved in the surrounding tissue – diapedetic perivascular hemorrhage , groups and siderofagov sideroblasts, pericellular and perivascular edema, perifocal proliferation of glia. Sclerosis and hyalinosis of arterioles and small arteries , in separate vessels, blood clots.

Anemic infarcts of the brain

 

 CONGESTIVE HEART FAILURE

Congestive heart failure has many causes that lead to a common final pathway of failure of the heart’s pumping function to provide sufficient blood to meet the metabolic demands of the perfused organs of the body. Initially, compensation to an increased stress is accomplished by ventricular hypertrophy, but when the reserve capacity is exceeded, cardiac failure ensues. Most cases begin as failure of the LV as manifest by fatigue and progressive pulmonary congestion. Failure of the right ventricle (RV) leads to increased central venous pressure, hepatic congestion, pleural and peri-cardial effusions, and pitting edema of the lower extremities. Cor pulmonale refers to isolated right heart hypertrophy and failure due to pulmonary vascular or parenchymal disease.

ANEURYSMS

An aneurysm is an external bulging of a vascular structure. Severe atherosclerosis is the cause of the relatively common abdominal aortic aneurysm as well as aneurysms of the descending thoracic aorta and iliofemoral arteries. Medial degenerative disease, also known as cystic medial necrosis, gives rise to dissecting hematoma (aneurysm) with origin in the ascending thoracic aorta (type A) or the transverse or descending thoracic aorta (type B), as well as nondissecting aneurysms of the ascending thoracic aorta. Medial degeneration develops as a result of a genetic defect, as in Marfan syndrome and Ehlers-Danlos syndrome, or as a result of hemodynamic stress accelerated by HTN. Both dissecting and nondissecting aneurysms are prone to external rupture leading to exsanguination. Infections of a major artery can give rise to mycotic (mushroomlike) aneurysms. Cardiovascular syphilis is a form of tertiary syphilis with ascending aortic aneurysm.

VALVULAR HEART DISEASE

Acute rheumatic fever (RF) is an acute multisystem disorder involving the skin, joints, brain, and heart that is triggered by an autoimmune reaction after streptococcal pharyngitis. Most of the inflammation resolves without consequence except for the distortion and subsequent wear and tear on the cardiac valves, particularly the mitral and aortic valves, giving rise months to years later to chronic rheumatic heart disease (RHD).

Infective endocarditis (IE) of the valvular or mural endocardium results from infection with microorganisms (bacteria, fungi, or rickettsia) that gain access through the gastrointestinal tract, skin, surgical instrumenta-

 to the bloodstream tion, or other means. Key clinical features of IE are fever and cardiac murmur, and positive blood cultures are confirmatory of the diagnosis. Acute IE is produced by highly virulent organisms, such as Staphylococcus aureus, involving a previously normal valve, whereas subacute IE is characterized by a more indolent clinical course with infection produced by a less virulent organism, such as Streptococcus viridans, often involving a previously diseased valve. In both acute and subacute IE, the infected vegetations produce destruction and incompetence of valves, CHF, and emboli to other organs.

A large variety of entities can produce valvular dysfunction, but the following figure prominently into the differential diagnosis. Mitral valve stenosis is virtually always due to RHD. Mitral valve incompetence (regurgitation) results from RHD, IE, or mitral valve prolapse due to myxomatous degeneration. Aortic valvular stenosis results from chronic RHD involving a 3-cusped valve, age-related (senile) sclerosis and calcification of a 3-cusped valve, or fibrosis and calcification of a congenitally tricuspid valve. Aortic valvular incompetence can develop from valvular lesions, such as IE, or aortic aneurysms producing distortion of the aortic annulus. Pulmonary and tricuspid valvular disease is produced by congenital defects and, less commonly, acquired causes.

MYOCARDIAL AND PERICARDIAL DISEASES

Myocarditis and pericarditis may be induced by infection with microorganisms (viruses, rickettsiae, bacteria, fungi, and protozoa) or noninfectious, immune-mediated processes. Bacterial infections produce neutrophil-rich suppurative inflammation. Viral infections are associated with lymphohistio-cytic infiltrates. Granulomatous inflammation may represent sarcoidosis or tuberculous infection. Myocarditis can produce heart failure or sudden death from arrhythmia. Pericar-dial involvement is often manifest as fibrinous pericarditis with a pericardial effusion.

Cardiomyopathies are diseases of the heart muscle. Etio-logically, primary cardiomyopathies are intrinsic diseases of the heart muscle, and secondary cardiomyopathies develop as a component of a defined disease process usually originating extrinsic to the myocardium. Pathophysiologically, cardiomyopathies are classified as dilated (congestive), hypertrophic, or restrictive. Dilated (congestive) cardiomy-opathy is characterized by progressive eccentric hypertrophy, cardiomegaly, and CHF. The condition may have a genetic basis or occur because of an acquired condition, such as viral myocarditis or long-term alcoholism. Hypertrophic cardiomyopathy is due to mutations in contractile protein genes and includes the classic idiopathic hypertrophic subaortic stenosis (IHSS) as well as other variants. Restrictive cardiomyopathy typically has a relatively normal-sized heart coupled with evidence of cardiac failure due to infiltration of the myocardium by amyloid material or –severe fibrosis.

Primary tumors of the heart occur at leas frequently than metastatic tumors of the heart, and most are

t 10 times lessbenign. The most common primary tumor of the heart in adults is the myxoma, which usually occurs in the left atrium and presents with symptoms mimicking mitral stenosis. The most common primary tumor of the heart in infants and children is the rhabdomyoma, which can produce a mass effect in the myocardium as well as ventricular cavity obstruction

 

CONGENITAL MALFORMATIONS OF THE HEART AND MAJOR VESSELS

A. Left-to-Right Shunts of the Circulation

Ventricular septal defect (VSD), membranous type; ventricular septal defect (VSD), muscular type; patent ductus arte-riosus (PDA); atrial septal defect (ASD), ostium secundum (patent foramen ovale) type; atrial septal defect (ASD), sinus venosus type (with partial anomalous pulmonary drainage of right pulmonary veins into right atrium); atrial septal defect (ASD), ostium primum type (partial endocardial cushion defect); atrioventricular septal defects (endocardial cushion defects), including complete atrioventricular canal defect; anomalous left coronary artery arising from pulmonary trunk; ruptured sinus of Valsalva aneurysm; other.

B. Right-to-Left Shunts of the Circulation

Tetralogy of Fallot; tricuspid atresia with ASD, VSD and/or PDA; total anomalous pulmonary venous connection (TAPVC) with ASD or PDA; transposition of the great vessels (congenital complete transposition of the great vessels) with VSD, ASD and/or PDA; persistent ductus arteriosus; aorticopulmonary septal defect; other.

C. Obstruction of the Circulation Without Shunt

Coarctation of the aorta, “infantile” form with tubular hypoplasia and “adult” postductal form; aortic arch and great vessel anomalies producing vascular rings around the trachea and esophagus; pulmonary stenosis; aortic valvular dysplasia and/or stenosis; supravalvular aortic stenosis; discrete subvalvular aortic stenosis; hypoplastic left heart syndrome; other.

 Other Lesions

Ebstein’s anomaly of the tricuspid valve; coronary artery anomalies, including origin of the left and right coronary arteries from a single right coronary ostium; other.

 

 

Ventricular Septal Defect: Membranous Type

Congenital heart disease results from malformations of the heart and major vessels that develop during embryogenesis and are present at birth. A general classification of congenital malformations of the heart and major vessels is presented in Table 2-1. The ventricular septal defect (VSD) is the most common malformation presenting in infancy and childhood. Most VSDs result from defective closure of the membranous interventricular septum, although some are located in the muscular interventricular septum. As a result of the left-to-right shunt, patients present with systolic murmur, CHF, and progressive pulmonary HTN. If not surgically corrected, pulmonary arterial pressure reaches the systemic level, and the shunt becomes predominantly right to left, leading to late onset of cyanosis (Eisen-menger syndrome).

 

Patent Ductus Arteriosus

Theductus arteriosus is an arterial connection between the origin of the left pulmonary artery and the aorta that normally closes within hours after birth. Failure of this connection to close results in PDA. PDA is another type of high-pressure left-to-right shunt producing symptomatic disease in infants and children. Other anomalies of

Atrial Septal Defects

Ostium secundum defect, the most common atrial septal defect (ASD), is located in the middle portion of the interatrial septum in the region of the foramen ovale. This ASD occurs as a result of defective formation of septum primum and septum secundum tissue, which leads to failure of the ostium secundum to close. Sinus veno-sus defect, located high in the interatrial septum, is the result of defective incorporation of the sinus venosus into the RV. This ASD is associated with anomalous drainage of the right upper lobe pulmonary veins into the right atrium. Failure of formation of the septum primum and septum secundum results in a common atrium. Because left-to-right shunting occurs at low pressure, patients with ASDs tend to have pulmonary HTN and become symptomatic later in childhood or as adults in contrast to the usual course of patients with VSDs and PDAs

Atrioventricular Septal Defects

Atrioventricular septal defects (AVSDs) result from significantly defective formation of endocardial cushion tissue. The ASD component is low in the interatrial septum because of failure of closure of the ostium primum. The VSD component is in the region of the membranous interventricular septum. The partial endocardial-cushion defect is composed of an ostium primum type of ASD, a

defective mitral valve with a cleft in the anterior leaflet, and subtle anomalies in the LV, but it is associated with a closed membranous interventricular septum. The complete endocardial-cushion defect, also called a persistent common atrioventricular canal, consists of a large ostium primum ASD, a membranous VSD, and an abnormal common atrioventricular valve straddling the AVSD

 

The tetralogy of Fallot is the most common form of cyanotic congenital heart disease, a state characterized by a right-to-left shunt with cyanosis at the time of presentation (i.e., cyanotic congenital heart disease). Depending on the severity of the defects, the presentation may occur in infancy (blue baby syndrome) but is not usually apparent until at least early childhood. The 4 componentsof the tetralogy of Fallot are (1) VSD; (2) obstruction of the right ventricular outflow tract, usually as a result of subpulmonic, infundibular stenosis; (3) an aorta that overrides the VSD; and (4) right ventricular hypertrophy. Complete surgical correction of the tetralogy of Fallot includes closure of the VSD and expansion of the right ventricular outflow tract

 

Transposition of the Great Vessels

Transposition of the great vessels, or more specifically, congeni-tally complete transposition of the great vessels, is a condition in which the aorta takes origin anteriorly from the RV and the pul-monic trunk arises posteriorly from the LV. Transposition of the great vessels is compatible with postnatal life only when the anomaly occurs in association with one or more other defects, usually

VSD, ASD, or PDA. The lower diagram shows the embryological development of transposition. Normally, two pairs of truncal swellings develop. In transposition, the wrong pair of truncal swellings becomes involved in partitioning the truncus, resulting in the abnormal position of the great vessels

 

ricuspid Atresia

Tricuspid atresia, a severe complex anomaly of the right side of the heart with underdevelopment (hypoplasia) of the RV and a right-to-left shunt through an ASD, a VSD, or a PDA, results in severe cyan-otic heart disease in infants. Next to transposition of the great vessels, it is the most common cause of severe cyanosis in the neonatal period, and the degree of cyanosis is usually more

 

 marked than in cases of transposition.

Coarctation of the Aorta

Coarctation of the aorta is a common obstructive congenital anomaly. There are 2 major types: (1) an infantile form, with tubular hypoplasia of the aortic arch proximal to a PDA, typically resulting in clinical problems in early childhood; and (2) an adult postductal form, in which there is a discrete ridgelike infolding of the aorta, just opposite the closed ductus arteriosus (the ligamen turn arteriosum). The postductal type of coarctation leads to the development of an extensive collateral circulation (top image) to bypass the obstruction. The patient presents with HTN in the upper extremities and normal pressures in the lower extremities. Rib notching (produced by the enlarged collateral arteries) is seen on chest radiograph.

   Aortic Atresia and Aortic Valvular Stenosis

Left ventricular outflow tract (LVOT) obstruction can result from aortic stenosis or atresia. In severe congential aortic malformation, LVOT obstruction leads to underdevelopment (hypoplasia) of the LV and ascending aorta. There is a dense, porcelainlike endocardial fi-broelastosis of the diminutive LV. The ductus arteriosus is open. This constellation of anomalies constitutes the hypoplastic left heart syndrome, a conlife when the ductus closes, unless high-risk surgery is performed. Less severe congenital aortic stenoses are compatible with longer survival. The congenital bicuspid aortic valve occurs in approximately 1 % to 2% of the population and can give rise to aortic stenosis in adulthood because of hemodynamic turbulence that leads to fibrosis and calcificationdition that is fatal in the first several days of postnatal

Atherosclerosis

The major pathologic and clinical effects of atherosclerosis involve the brain, the kidneys, the aorta, the peripheral and visceral arteries, and the heart. According to the response to injury hypothesis, atherosclerosis develops as a response of the vessel wall to multifacto-rial and repetitive injury. Genetic susceptibility, environmental factors, and endogenous metabolic alterations are risk factors that participate in the pathogenesis of atherosclerosis and the formation Atherosclerosis, the most prevalent and important form of arte- of atherosclerotic plaques in vessels. Atherosclerosis progresses asymptomatically for years until a clinical threshold is reached. The onset of symptoms may be gradual or abrupt. The major treatable risk factors for development of atherosclerosis are a diet high in saturated fats and cholesterol, HTN, cigarette smoking, and diabetes mellitus.

 

 

Pathologic Changes in Coronary Artery Disease

Coronary heart disease (atherosclerotic or ischemic heart disease), dysfunction and damage to the heart muscle resulting from coronary artery disease (CAD), is usually due to coronary atherosclerosis. Coronary atherosclerosis leads to progressive luminal narrowing of one or more of the coronary arteries by atherosclerotic plaques; these frequently have calcification. Coronary reserve is such that angina pectoris usually does not develop until there is at least 75% narrowing of the cross-sectional area. Most symptomatic disease is associated with the development of secondary changes in the plaques, especially surface ulceration, intraplaque hemorrhage, and thrombosis. Coronary thrombi can organize, leading to recanalization of the lumen. Nonatheromatous causes of my-ocardial ischemia include congenital coronary anomaly, coronary dissection, coronary vasculitis (Kawasaki disease, polyarteritis nodosa, and others), or a systemic hemodynamic problem, such as severe shock or profound anemia.

Acute and Subacute Myocardial Infarcts

Angina pectoris, which is due to myocardial ischemia of short duration (approximately 15 minutes), results in reversible myocardial injury. Myocardial infarction, the death of heart muscle due to prolonged, severe ischemia, usually involves the LV. Myocardial necrosis generally begins after 45 minutes of severe ischemia and extends from the subendocardium into the subepicardium in a wave-front fashion over a period of approximately 3 to 4 hours

Subendocardial (intramural) myocardial infarcts are limited to the inner half of the wall. Transmural myocardial infarcts extend into the outer half of the wall. Lesions of the left anterior descending coronary system give rise to anterior and anteroseptal myocardial infarcts; lesions of the right coronary artery give rise to inferior (pos-teroapical) and posterior myocardial infarcts. Lesions of the left circumflex coronary artery give rise to lateral myocardial infarcts.

Healed Myocardial Infarcts

Acute myocardial infarction may result in death due to pump failure or ventricular fibrillation. If the patient survives, the infarct undergoes organization and healing. During the first 2 to 3 weeks, the necrotic myocardium is gradually replaced by granulation tissue; during the next 2 to 3 months, the granulation tissue is converted to fibrous scar. This illustration shows various patterns of healed myocardial infarcts. During healing, the thinned infarcted wall may expand to form a ventricular aneurysm. Mural thrombi can form over the infarct and give rise to systemic emboli.

 

 

 

Causes of Hypertension

Increase of systemic arterial pressure greater than the normal values of 120 mm Hg systolic and 80 mm Hg diastolic leads to a constellation of changes known as hypertensive cardiovascular disease. The pathophysiologic basis of HTN is excessive arteriolar constriction leading to increased peripheral vascular resistance. This may be exacerbated by factors promoting increased cardiac output. The fundamental etiology of HTN is unknown in most patients, although genetic predisposition and certain environmental influences, particularly high sodium intake, are known to be important factors. This condition is known as essential, idiopathic, or primary HTN. In approximately 10% of patients, HTN is secondary to a recognizable lesion or disease. Parenchymal renal disease and renovascular disease are the most common of these entities that are amenable to surgical treatment. Endocrine disorders and coarc-tation of the aorta are less common by amorphous eosinophilic material

 

The Kidneys in Hypertension: Benign and Malignant

 

The natural history of HTN follows 2 general patterns. Benign HTN is characterized by mild to moderate increase of blood pressure and an asymptomatic period of several years before the inevitable onset of symptoms and end-organ damage (hence, the condition is not truly benign). Malignant HTN is characterized by marked increase of blood pressure and rapid progression over a few weeks to end-organ failure. Most patients with essential HTN follow the benign pattern, although it may accelerate to malignant HTN. The characteristic vascular lesion of benign essential HTN is widespread hyaline arteriolosclerosis manifest by thickening of the walls of the small arteries and arterioles composed of degenerated smooth cells and deposited plasma proteins. Hyaline arteriolosclerosis with associated small cortical scars (hyaline arteriolonephrosclerosis) is commonly seen in the kidneys. Hyperplastic arteriolosclerosis, marked luminal narrowing by cellular intimal proliferation in a lamellar, “onionskin” pattern, is the characteristic lesion of malignant HTN. In severe malignant HTN, fibrinoid necrosis of the glomerular arterioles occurs. An associated ischemic injury develops rapidly, leading to petechial hemorrhages in multiple organs, including the kidneys (hyperplastic arteriolonephrosclerosis).

 

The Heart in Hypertension: Concentric Hypertrophy,

Hypertension, even of moderate degree, leads rapidly to cardiac hypertrophy, a compensatory increase of mass of the LV. The typical pattern of concentric hypertrophy of the LV, characterized by a thick wall and a relatively small chamber volume, is produced by a pressure load (afterload) on the ventricle. The heart s silhouette is relatively normal, but the ECG shows increased voltage. When the limits of compensation are reached, the patient may have progressive cardiac decompensation accompanied by cardiac dilation. Cardiac hypertrophy is an independent risk factor for ventricular arrhythmias and sudden cardiac death.

 

Pathophysiology of Heart Failure

 

Heart failure is a state in which the heart fails as a pump to provide sufficient volume of circulating blood to meet the metabolic demands of the body. Because the dominant symptoms usually result from pulmonary or systemic venous congestion, the condition is termed congestive heart failure (CHF). Most commonly, heart failure is of the low cardiac output variety, but some conditions, including thiamine deficiency (beriberi), thyrotoxicosis, and severe anemia, produce cardiac failure with an increased circulating blood volume (high output cardiac failure), as shown here. The failure may be left-sided, right-sided, or combined left- and right-sided heart failure. This illustration shows the major manifestations of failure of the left and right ventricles. Cardiac transplantation or an artificial heart is the last therapeutic option. The most common conditions necessitating cardiac transplantation are end-stage ischemic heart disease (ischemic cardiomyopathy) and dilated (congestive) cardiomyopathy.

 

 

Left-Sided Heart Failure: Eccentric Hypertrophy

Most cases of CHF result from diseases that affect the LV initially or primarily, most commonly HTN and CAD. In response to chronic stress, the affected part of the heart undergoes compensatory hypertrophy. When the heart reaches a critical weight of 550 g, reserve is lost and progressive cardiac decompensation ensues. Heart failure results in progressive ventricular dilatation superim- posed on the hypertrophy, which produces a pattern of so-called eccentric hypertrophy, as shown here. A severe acute load on the heart can produce failure and cardiac dilatation without previous hypertrophy. Stress of the atria can result in atrial fibrillation and formation of mural thrombi. The frequent coexistence of HTN and CAD can result in myocardial infarction of the hypertrophied LV.

issecting Aneurysm of the Aorta

The effects of HTN with excessive hemodynamic trauma on a weakened aortic wall can lead to the formation of a hematoma in the media. The hematoma dissects longitudinally to split the media, which creates a dissecting hematoma or a dissecting aneurysm, a double-barreled aorta with true and false lumens. In most cases, a proximal intimal tear allows blood to enter the false lumen under systemic pressure. In type A dissections, the proximal intimal tear is in the ascending thoracic aorta, whereas in type В dissections, the proximal intimal tear is in the aortic arch or the descending thoracic aorta. Type A dissections, which are prone to external rupture into the mediastinum or pericardial cavity, necessitate surgical intervention. Some dissections develop distal tears and become chronic with the potential for late rupture. Blood pressure control is key in the treatment of any aortic dissection.