digest on pathomorhology

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The iron required for hemoglobin synthesis is derived from 2 primary sources - ingestion of foods containing iron and recycling of iron from senescent red cells.

Iron is absorbed mainly in the duodenum and proximal jejunum. Iron from diet containing hem is better absorbed than non-hem iron.

Absorption of non-hem iron is enhanced by factors such as ascorbic acid (vitamin C), citric acid, amino acids, sugars, gastric secretions and hydrochloric acid.

Iron absorption is impaired by factors like medicinal antacids, milk, pancreatic secretions, phytates and tannates contained in tea.

Non-hem iron is absorbed almost exclusively as ferrous form. Iron balance in the body is maintained largely by regulating the absorptive intake by intestinal mucosal cells, so called mucosal block.

Pathogenesis

It is only after the tissue stores of iron are exhausted that the supply of iron to the marrow becomes insufficient for hemoglobin formation, iron deficiency anemia develops. One or more of the following factors may cause it:

1.Increased blood loss.

Uterine e.g. excessive menstruation in reproductive years, repeated miscarriages, at onset of menarche, postmenopausal uterine bleeding.

Gastrointestinal e.g. peptic ulcer, hemorrhoids, hookworm infestation, cancer of stomach and large bowel, oesophageal varices, hiatus hernia, chronic aspirin ingestion, ulcerative colitis, diverticulosis.

Renal tract e.g. hematuria, hemoglobinuria.

Nose e.g. repeated epistaxis.

Lungs e.g. hemoptysis.

2.Increased requirements.

Spurts of growth in infancy, childhood and adolescence.

Prematurity.

Pregnancy and lactation.

3.Inadequate dietary intake

Poor economic status.

Anorexia e.g. in pregnancy.

Eldery individuals due to poor dentition, apathy and financial constraints.

4.Decreased intestinal absorption.

Partial or total gastrectomy

Achlorhydria

Intestinal malabsorption such as in celiac disease.

Clinical features

Peripheral blood. Red cells are pale (hypochromic) and smaller than normal (microcytic).

Marrow. Hyperplasia of normoblasts, associated with loss of sideroblasts and absence of stainable iron in the reticuloendothelial cells.

Others organs. Alopecia, koilonychias, atrophies of the tongue and gastric mucosa. Esophageal webs may appear, completing the Plummer-Vinson triad of hypochromic microcytic anemia, atrophic glossitis, and esophageal webs. Chlorosis (called so because of pale greenish color of skin in this disease).

Megaloblastic anemia

There are two principal types of megaloblastic anemia:

1.Pernicious anemia, the major form of vitB12 deficiency anemia.

2.Folic acid deficiency anemia.

VitB12 and folic acid are necessary factors of hemopoiesis. VitB12 enters the organism through the intestinal tract. Absorbtion of vitB12 takes place in stomach, when it has the Castle‟s intrinsic factor. Additional cells of fundal glands of the stomach produce it. The connection of vitB12 and

Castle‟s intrinsic factor leads to formation of the complex of protein and vitamin. It is absorbed through mucosa of stomach and ileum. Entrance of vitB12 and active folic acid to bone marrow determines normal erythropoesis and activates maturation of red blood cells.

Pernicious anemia

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If the additional cells of fundal glands don’t product gastromucoprotein the anemia is called pernicious anemia (PA).

Addison and Birmer described it in 1868. It is catching hereditary. The additional cells are injured. They are involuated prematurely.

The autoimmunity injury of additional cells takes place in this case too. There are antibodies against the additional cells (gastric parietal cells).

As a result of deficiency of these cells the erythropoiesis is done in megaloblastic type.

The processes of destruction predominate on the processes of hemopoiesis in this case.

Megaloblastic and megalocytic disintegrate in bone marrow and in the focuses of extramedullar hemopoesis and in the blood vessels too.

Morphology

There is general hemosiderosis as a result of disintegration of red blood cells.

There is a fatty change in the parenchymatous organs as a result of hypoxia grows.

The major specific changes in PA are found in bone marrow, alimentary tract and central nervous system.

In the alimentary system abnormalities are regularly found in the tongue and stomach. The tongue is shiny, glazed, and “beefy” (atrophic glossitis). The changes in the stomach are following: the mucosa is thin, plain; its wrinkles are smooth away. The glands are decreased. The epithelium is atrophied. These changes lead to sclerosis.

The liver increases in size, has a density consistence and a brown color (hemosiderosis). Pancreas has a density consistence too (sclerosis).

The principal alterations involve the spinal cord, where there is myelin degeneration of the dorsal and lateral tracts, sometimes followed by loss of axons. These changes give rise to spastic paraparesis, sensory ataxia, and sever paresthesias in lower limbs.

Folic acid deficiency anemia

Folic acid deficiency induces a megaloblastic anemia that is clinically and hematologically indistinguishable from that encountered in vitamin B12 deficiency. However, neurologic changes seen in the latter do not occur and gastric atrophy is absent.

Hypoplastic and aplastic anemias

Characterized by failure or suppression of multipotent myeloid stem cells and resultant neutropenia, anemia, and thrombocytopenia (pancytopenia). May be idiopathic or caused due to following factors:

Endocrine (hypothyroidism, thymus tumors).

Radiation lesions (x-rays, radium radiation, atomic energy).

Chemical (benzene, cytostatic preparations, etc.

Toxicoallergic (drugs).

Infectious.

Destruction of the bone marrow by cancer metastases.

Morphology

Hypocellular marrow.

Hematopoetic cells replaced by fat cells.

Secondary effects of granulocytopenia (infections) and thrombocytopenia (bleeding).

III.Anemia by increased rate of destruction of red blood cells (RBC) - hemolytic anemia.

The process of destruction is predominated.

There are general hemosiderosis and hemolytic jaundice.

As a result of hemolysis of erythrocytes there is hyperplasia of bone marrow. It has a pinkred color.

There are many foci of extramedullar hemopoesis in lymphatic nodules, connective tissue and spleen.

There are two groups of this type of anemia.

1.Hemolytic anemia with intravascular hemolysis predominates.

There are the following courses of this type such as hemolytic poisons, hard burns, malaria, sepsis, and complications after hemotransfusions and transfusion of incompatible blood groups. These anemias generate large amounts of free hemoglobin in circulation. Since this

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free hemoglobin can‟t be taken up fast enough by the phagocytic cells of the liver and spleen, it is excreted through the glomeruli, causing hemoglobinuria.

Hemoglobin in the primary glomerular filtrate is partially taken up by the proximal tubular cells and transformed into the hemosiderin inside the lysosome, causing renal hemosiderosis.

Acute hemolytic anemia develops in poisoning with hemolytic poisons (mushrooms, venom of snakes, phosphorus, etc.), in burns, sepsis, malaria, transfusion of incompatible blood, fetal erythroblastosis. The latter occurs due to Rh incompatibility of the mother‟s and fetus‟s blood.

2.Hemolytic anemia with extravascular hemolysis. Intrinsic defects (usually hereditary) are divided into three groups, such as

1)Defects of cell membrane. This group includes hereditary spherocytosis, elliptocytosis.

2)Defects of enzymes. Activity of enzymes decreases. And as a result of this erythrocytes are destructured

3)Defects of molecular structure of hemoglobin (hemoglobinopathies). In some hereditary disorders, the molecular structure of hemoglobin is abnormal.

It includes the following forms of the disease: congenital (family) spherical-cell anemia, sickle-cell anemia, thalassemia, or Cooley's anemia.

Spherical-cell anemia is characterized by congenital spherocytosis (erythrocytes are small, spherical, brightly colored, without light center, with decreased resistance). These abnormal erythrocytes are destroyed. The first sign of the disease is jaundice; it is followed by splenomegaly and anemia.

Sickle-cell anemia and thalassemia are hemoglobinopathies (conditions due to abnormal hemoglobin in the erythrocytes). The cause of sickle-cell anemia is congenital insufficiency of erythrocytes due to presence of S hemoglobin (S corresponds to sickle). The condition is characterized by presence of sickle-like erythrocytes revealed during crisis; they cause stasis, hemorrhages, and infarctions. Siderofibrosis caused by hemosiderin accumulation develops due to increased decay of sickle-like erythrocytes in the spleen. :

Thalassemia (target cell anemia, Cooley‟s anemia). It occurs in children and is characterized

DISEASES OF CARDIOVASCULAR SYSTEM

ATHEROSCLEROSIS

Atherosclerosis is a multifactorial disease that affects the intima of elastic arteries. The disease is characterized by intramural deposits of lipids, proliferation of vascular smooth muscle cells and fibroblasts, and accumulation of macrophages.

Basic lesion is the patchy deposition of yellow lipid in plaques deep in the intima with overlying fibrosis up to 1,5 cm in diameter, protruding into the vessels lumen. It is called atheroma, i.e. it is essentially an intimal disease.

The term AS derives from the combination of athero - („porrige‟), referring to the soft, lipidrich material in the center of a typical intimal plaque, and sclerosis (scarring),referring to the connective tissue components.

The major clinical syndromes are related with ischemia, which is produced by narrowing of the vascular lumen (coronary heart disease, peripheral vascular disease, cerebral infarction), or from weakening of the arterial wall leading to aneurysm.

Atherosclerosis begins early in life and develops progressively over years, it is rarely symptomatic in the first three decades, but thereafter the frequency of clinical atherosclerotic events increases logarithmically. Because of its prevalence, as can be considered epidemic in industrialized nations.

Every year approximately 1 million persons in the world experience either a myocardial infarct or sudden cardiac death. Nearly all of them are the result of atherosclerotic coronary disease.

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Background etiological factors influencing the rich of or susceptibility to atheroma are multiply and interrelated. The major background factors may be grouped into two main

categories:

I Endogenous (not modifiable) 1. Sex

Atherosclerotic coronary heart disease is predominantly a disease of men. Especially in younger ages; the prevalence in men in the fourth decade is three times that in women. Possible explanations for the sex differences include levels of estrogenic hormones and higher levels of highdensity lipoprotein, which is known to be antiatherogenic, in premenopausal women then in men.

2. Genetic factors (Heredity)

Evidenced in cases with clearly defined abnormalities of lipid metabolism. Apparent genetic roles in familial predisposition to AS may be related to genetic effects on other risk factors, especially hyperlipoproteinemia, hypertension and diabetes mellitus.

IIEnvironmental (modifiable)

1.Diet.

Many studies have demonstrated the specific effects of diet on lipid and lipoprotein levels, including the amount of dietary cholesterol ingested, the total number of calories from carbohydrates, protein and fat, and the intake of alcohol and concentrated sweets (anti-oxidants including red wine reduce the risk).

2. Metabolic diseases.

There are diabetes mellitus, myxedema, nephrosis, xanthomatosis, familial hyper cholesteronemia.

Hypertension.

Cigarette smoking.

The component of cigarette smoking responsible for the acceleration of atherosclerotic events is not known. It may be related to effects of the cigarette smoking on thrombosis or to increased concentration of carboxygemoglobin in the blood of smokers.

3.Lack of physical exercise.

4.Other risk factors.

Other risk factors suggested being associated with AS obesity, physical activity, hyperglycemia, stress, and coffee consumption.

These factors may act as increased blood lipids-cholesterol and lipoproteins. The risk is correlated with elevated low-density lipoprotein (LDL), formed from the catabolism of very-low- density lipoprotein (VLDL) to a cholesterol ester-protein core that carries some 70% of the total serum cholesterol. Atheroma is specifically associated with high blood low-density lipoprotein levels (as well as total cholesterol levels). Risk is inversely related to the high-density lipoprotein (HDL) levels, perhaps because HDL helps clear cholesterol from vessel lesion.

Pathogenesis of AS has three stages:

1.Endothelial injury is accompanied by the attachment of monocytes, platelets, and thrombus formation.

2.Macrophages in the intima phagocytise lipid and transform into foam cells. Macrophages also secrete growth factors that stimulate the proliferation of smooth muscle cells.

3.Ruptured atheromas release thrombogenic material into the circulation, causing thrombus for intimal ulceration.

Classification AS has the following microscopically stages (phases):

1.Pre-lipid stage is characterized by mucoid swelling of intima and accumulation of plasma proteins, and glycosaminoglycanes, the destruction of endothelium and elastic and collagen fibers of intima's basal membrane.

2.Stage of fatty stripes (lipoidois). Fatty stripes appear on intima due to its lipid infiltration, lipoproteins and proteins fixation. Lipids impregnate intima and are accumulated in macrophages. Macrophages that have accumulated lipid in their cytoplasm appear histologically as csantomic or foam cells. Elastic membranes become swollen, their destruction occurs,

3.Stage of liposclerosis. Macrophages secrete growth factors and cytokines, which recruit additional monocytes, macrophages and other cells. Cytokines and growth factors also

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Berry aneurysm. Spherical dilatation due to congenital wall weakness, generally less than 1.5 cm in diameter, typically in the circle of Willis.

Saccular aneurysm. Large spherical dilatation up to 20cm in diameter, often at least partially filled with thrombus. The etiology is usually atherosclerosis.

Fusiform (cylindroid) aneurysm. Gradual lumen dilatation generating a spindleshaped lesion up to 20 cm in diameter, and to the full length of the aorta. AS is the most common cause.

Dissecting aneurysm. Blood enters the arterial wall through a tear, usually in the aortic arch, and dissects the layers-typically between the middle and outer thirds of the media.

HYPERTENSION

In medically advanced countries, hypertension is the most common serious chronic disease, affecting about a half of the population over 50 years of age. Arterial hypertension is defined clinically as borderline when it riches 140/90 mm Hg and hypertensive when 165/95 mm Hg.

There is elevation of systolic pressure alone, (systolic hypertension) or elevation, of both systolic - and diastolic pressure (diastolic hypertension), both have an increased risk of serious complications, but diastolic hypertension is more dangerous.

Hypertension is classified into two types:

1.In 90-95% of all cases of hypertension, no cause can been established – such cases are called essential or idiopathic or primary.

2.In only 5-10% of all cases of hypertension is any disease, which may be associated with disturbance of these mechanisms detectable – such cases are secondary hypertension. Examples:

Kidney diseases.

Hyperfunction of adrenal cortex (Cushing „s syndrome – corticosteroid excess).

Tumor of adrenal medulla (pheochromocytoma) – catecholamine excess.

Hypertension occurs in toxemia of pregnancy.

This hypertension comprises 5-10% causes of disease.

If these causes of secondary hypertension were eliminated, hypertension disease would be

cure.

According to the clinical course, both types of hypertension may be benign or malignant.

1.Benign hypertension is moderate elevation of blood pressure and the rise is slow as the years pass. About 90% of patients of hypertension have benign disease.

2.Malignant hypertension is marked and rapid increase of blood pressure to 200/140 mm Hg or more and the patients have papilledema, hemorrhages and hypertensive encephalopathy.

All the above mechanisms are essentially vaso-constrictor. The possible roles of vaso-dilator mechanisms – for example the effect of nitric oxide on vascular smooth muscle – are being currently researched.

The increased peripheral resistance resulting in sustained hypertension may arise from:

1.Increased sympathetic tone.

2.Increased release of renin and generation of angiotensin.

3.The presence of vasoconstrictive substances in the circulation.

4.Increased sodium load and extracellular fluid load, and finally.

5.A postulated excessive responsiveness to the other factors.

Morphology

It is important to realize that the central lesion in most cases of hypertension is a decrease in the size of the lumen in small muscular arteries and arterioles, the resistance vessels that control the flow of blood through the capillary bed.

The lumen may be restricted by active contraction of the vessel wall, an increase in the structural mass of the vessel wall, or both.

The morphologic changes associated with moderate elevations of blood pressure are too subtle to be detected by simple histological studies. Small muscular arteries show segmental dilatation as a result of necrosis of smooth muscle cells.

The combination of cell necrosis and deposition of plasma proteins in the vessel wall is termed fibrinoid necrosis.

The period of acute injury is rapidly followed by smooth muscle proliferation and a striking increase in the number of layers of smooth muscle cells, which yields the so-called onionskin appearance. Taken together, these changes are labeled malignant arteriosclerosis or malignant arteriolosclerosis, depending on the size of the vessels affected.

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Clinical-morphological stages

1.Subclinical stage occurs by hypertrophy of muscular layer and elastic structures of arterioles and small-sized arteries, spasm of arterioles. At this stage the hypertrophy of the left ventricle of heart begins.

2.A stage of general changes of arteries begins as arterial pressure increases. Arteriolar walls permeability is increased, it results in plasmatic impregnation and hyalinosis. Elastic, muscular-elastic and muscular arteries walls undergo elastofibrosis and atherosclerosis. Elastofibrosis is characterized by a hyperplasia and breaking of internal elastic membrane and spreading of connective tissue. Atherosclerotic changes in case of hypertension are more extensive, the process reaches small-sized arteries of muscular type, plaques are more often circular, that cause acute mechanical stenosis of the vessel.

3.The stage of secondary changes of organs is developed in connection with changes of arteries and insufficiency of the intraorganic blood circulation. These changes develop slowly, that results in atrophy of parenchyma and sclerosis (it’s characteristic of benign hypertension), quickly (spasm, thrombosis, fibrinoid necrosis) and causing infarctions and hemorrhages (it’s characteristic of malignant hypertension).

The main clinical-morphological forms of essential hypertension

1.Cardiac form

Hypertensive heart disease or hypertensive cardiomyopathy is the disease of the heart resulting from systemic hypertension of prolonged duration and manifesting by left ventricular hypertrophy.

Often hypertension predisposes to atherosclerosis. The arterial changes and vascular complications increase with the severity and duration of the hypertension, but are modified by genetic factors, environmental factors, sex (females tolerate hypertension better), and associated diseases.

Macroscopically, the most significant finding is marked hypertrophy of the heart, especially of the left ventricle. Weight of heart reaches 1 kg, thickness of left ventricle walls is up to 3 cm, the papillary muscles are rounded and prominent, and the cardiac chamber is small (concentric hypertrophy). But when decompensation and cardiac failure develop, there is eccentric hypertrophy (myogenic dilation) with thinning of the ventricular wall and dilation of the left ventricular and atrial cavities.

There may be dilatation and hypertrophy of right heart as well. Heart is called “cor bovinum”.

2.Cerebral form (Cerebrovascular diseases.

It is characterized first of all as impairment of cerebral blood circulation. This hypertension can result in two main types of parenchymal diseases of the brain:

1)Ischemic brain damage (hypoxic encephalopathy and cerebral infarction).

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.

Cerebral infarction may be anemic or hemorrhagic.

Macroscopically, an anemic infarct becomes evident 6 - 12 hours after its occurrence. The affected area is soft and swollen and there is blurry of junction between gray and white matter. Within 2-3 days, the infarct 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.

2)Intracranial hemorrhage (intracerebral and subarachnoid hemorrhage).

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Hemorrhage into the brain of patient with hypertension is intracerebral hemorrhage, which is usually of hypertensive origin due to rupture of microaneurysm.

The common sites of hypertensive intracerebral hemorrhage are the region of the basal ganglia, medulla and cerebellum 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. Patients can be paralyzed.

3.Renal form

Renal form is characterized by chronic arteriolo-sclerotic nephrosclerosis.

Kidneys have a term “primary shrunken kidneys”.

Macroscopically, both kidneys are affected equally and are reduced in size and weight, often weighting about 6 gm. The capsule is connected densely to the cortical surface. The surface of the kidney is finely granular and shows V-shaped areas of scarring. The cut surface shows firm kidney and narrowed cortex.

Microscopically, there are primary diffuse vascular changes, which produce parenchymal changes and secondary as a result of ischemia. There is variable degree of atrophy of parenchyma; these include glomerular shrinkage, deposition of collagen in Bowman's space, periglomerular fibrosis.

Clinical features are variable, elevation of the blood pressure with headache, dizziness, and palpitation.

Renal failure and uremia may occur.

In case of malignant hypertension can develop as hypertonic crisis - acute increase of arterial pressure in communication (connection) with spasm of arterioles.

Morphological appearance of hypertonic crisis: plasmatic impregnation or fibrinoid necrosis of arteriolar walls.

The causes of death among hypertensive patients are the following:

Congestive heart failure.

Coronary artery disease.

Cerebrovascular accidents.

Uremia.

Causes unrelated to hypertension. The cardiac complications therefore account for 36% of the death.

ISCHEMIC HEART DISEASE

Ischemic heart disease (IHD) is the generic designation for a group of closely related syndromes resulting from ischemia – an imbalance between the supply and demand of the heart for oxygenated blood. Ischemia comprises not only insufficiency of oxygen (hypoxia, anoxia) but also reduced availability of nutrient substrates and inadequate removal of metabolites. Because coronary artery narrowing or obstruction owing to atherosclerosis underlies myocardial ischemia in the vast majority of cases, IHD is often termed coronary artery disease (CAD) or coronary heart disease (CHD).

The etiology and pathogenesis

Etiology of IHD is identical to the one of atherosclerosis and hypertension. Direct reasons of development of the myocardial infarctions are spasms of vessels, thrombosis or thromboembolism of coronary arteries of heart. Pathogenic factors (factors of risk) are:

1.Hyperlipidemia;

2.Arterial hypertension;

3.Steatosis;

4.Hypodynamia;

5.Smoking;

6.Impairments of tolerance to carbohydrates;

7.Diathesis;

8.Genetic predisposition;

9.Sex-binded.

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Depending on the rate of development and ultimate of the arterial narrowing and the myocardial response, four ischemic syndromes may result:

1.Angina pectoris.

2.Myocardial infarction.

3.Sudden cardiac death.

4.Chronic ischemic heart disease.

Acute Ischemic Heart Disease (AIHD)

Angina pectoris

It is a symptom complex of IHD characterized by paroxysmal attacks of substernal or pericordial chest discomfort (variously described as constricting, squeezing, choking, or knife-like) caused by transient (15 sec. to 15 min.) myocardial ischemia that falls short of inducing the cellular necrosis that defines infarction.

There are three somewhat distinctive patterns of angina pectoris, differentiated on the basis of the provocation and severity of the pain:

1.Stable (typical) angina pectoris appears to be reduction of coronary perfusion to a critical level by chronic stenosing coronary atherosclerosis; this renders the heart vulnerable to further ischemia whenever there is increased demand, such as that produced by physical activity, emotional excitement, or any other cause of increased cardiac workload.

2.Prinzmetal’s variant refers to a pattern of episodic angina that occurs at rest and has been documented to be due to coronary artery spasm.

3.Unstable angina refers to a pattern of pain that occurs with progressively increasing frequency, is precipitated with progressively less effort, often occurs at rest, and tends to be of prolonged duration. This syndrome is sometimes referred to as preinfarction or acute coronary insufficiency. Unstable angina is induced by fissuring, ulceration, or rupture of an atherosclerotic plaque with superimposed partial thrombosis and possibly embolization or vasospasm.

Acute myocardial infarction (MI)

Acute myocardial infarction also known as “heart attack”, is overwhelmingly the most important form of IHD in industrial nations.

Pathogenesis. At least 90% of transmural acute MI are caused by an occlusive intracoronary thrombus overlying an ulcerated or fissured stenotic plaque. Occlusion of a major coronary artery results in ischemia throughout the anatomic region supplied by that artery, most pronounced in the subendocardium. The function becomes strikingly abnormal within 1 min after ischemia, but myocardial coagulation necrosis occurs only after 20 to 40 min of severe ischemia.

Classification of Myocardial infarction

I. According to localization: left ventricle, right ventricle, and right atrium, left atrium.

Infarctions are most frequently located in the left ventricle. Besides it may be located in other parts of heart, but this is observed rarely. The region of infarction depends upon the area of obstructed blood supply by one or more of the three coronary arterial trunks:

1)Stenosis of the left anterior descending coronary artery is the most common (40-50%) - the infarctions of the anterior wall of left ventricle near apex or anterior two-thirds of interventricle septum.

2)Stenosis of the right coronary artery is the next most frequent (30-40%) - interior/posterior wall of left ventricle; posterior one-third of interventricular septum, posterior right ventricular free wall in some cases.

3)Stenosis of the left circumflex coronary artery is seen least frequently (15-20%) - lateral wall of left ventricle.

II. According to the anatomic region of the left ventricle: anterior, posterior, lateral, septal and circumferential.

III. According to the degree of thickness of the ventricular wall:

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1.Full-thickness or transmural, in which the ischemic necrosis involves the full or nearly full thickness of the ventrical wall in the distribution of a single coronary artery. As a result the rupture of cardiac wall, endocarditis with thrombus and fibrinous pericarditis can develop.

2.Subendocardial or lamina constitutes an area of ischemic necrosis limited to the inner onethird or at most one-half of the ventricular walls, often extending laterally beyond the perfusion territory of a single coronary artery.

3.Subepicardial is rare infarction. In region of it fibrinous inflammation of pericardium

develops. It is called reactive pericarditis. IV. According to the duration of infarctions:

1.Acute myocardial infarction develops in the first time (during 8 weeks from beginning of ischemic necrosis).

2.Repeated myocardial infarction develops after 8 weeks of acute infarction.

3.Recurring (recidivic) myocardial infarction develops during 8 weeks of acute infarction.

Morphology

The macroscopic and microscopic changes in the myocardial infarction correspond to the age of the infarct.

In 6-12 hours the lesion may have a slight pallor but may be inapparent; however, changes in as early as 3 to 6 hours may be accentuated by use histochemical techniques.

By 18-24 hours infracted tissue is pale to cyanotic.

During first week the lesion becomes progressively more sharply defined, the color of infarction is charged from cyanotic red to bright yellow or yellow-green. The consistency of infarct in this period is soft.

A circumferential rim of hyperemic granulation tissue that progressively expends may be seen by 7 to10 days.

Fibrous scar is well established by 6 weeks. It is thin, gray-white, hard, shrunken fibrous scar.

Microscopically, within one hour of ischemic injury, there is intercellular edema, and myocytes become wavy and buckled. This is attributable to stretching of noncontractile dead fibers by adjacent viable contracting myocytes. In addition, border-zone viable cells show fine lipid droplets and large cytoplasmic vacuoles called vacuolar degeneration or myocytolysis. At this stage, typical coagulative necrosis is not yet evident.

In 12 to 72 hours a neutrophilic infiltrate into necrotic tissue with progressive evolution of characteristic eosinophilic coagulative necrosis can occurs.

Between 3 and 7 days dead myocytes begin to disintegrate and are resorbed by macrophages and enzyme proteolysis.

At 7 to 10 days granulation tissue appears and progressively replaces necrotic tissue, ultimately generating a dens fibrous scar.

In fourth to sixth week increased fibrous tissue, decreased blood supply, fewer pigmented macrophages, lymphocytes and plasma cells are seen.

Complications of infarction

Complications of infarction depend on the size and location of the necrosis, as well as the reserve of functional myocardium.

1.Arrhythmias are the most common form of complication in acute myocardial infarction (75 to 95%).

2.Left ventricular congestive failure and mild-to-severe pulmonary edema (60%).

3.Cardiogenic shock (10%).

4.During the first weak the heart rupture may develop, which is often fatal. Rupture of the free wall causes pericardial hemorrhage and tamponade. Rupture of the septum produces a left-to right shunt with right heart volume overload.

5.Fibrinous pericarditis appears on the second day of myocardial infarction.

6.About 3 - 4% of patients who suffered from acute myocardial infarction develop postmyocardial infarction syndrome, which is characterized by pneumonitis.

7.Mural thrombosis and thromboembolism from intracardiac thrombi and thrombosis in the leg veins is observed in 15-45% cases of acute myocardial infarction.