Atherosclerosis and arteriosclerosis
Ischemic heart disease classification, clinical-morphological description. Myocardial infarction: causes, classification, dynamics of morpho-functional manifestations in myocardium.
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.
Hypertensive disease (HI) or essential hypertension is a chronic disease with increase of arterial pressure. Symptomatic (Secondary) hypertension occurs at diseases of the nervous system, kidneys and vessels. Types of secondary hypertension also distinguished are: kidney (nephrogenic, renal vasculitis), endocrine (disease/syndrome of Icenko-Cushing, primary aldosteronism, to pheochromocytoma), neurogenic (trauma, tumor, abscess, hemorrhage in a cerebrum, defeat of hypothalamus and barrel of brain), vascular (coarctation of aorta, other anomalies of vessels, polycytemia).
Etiology and pathogenesis of hypertensive disease is not fully known. That factor which needs to be considered as the starting one, as a result of whose action arterial pressure begins to exceed critical border – 140 and
All factors which are able to increase the cardiac output or peripheral resistance or both simultaneously can be considered as the etiologic factors of hypertensive disease. To the majority of them belong: the increase of the volume of plasma, the increase of the cardiac output, the hyperactivity of the sympathetic nervous system, the breach of kidney functions.
Sympathetic hyperactivity -is one of the strongest factors of the development of the essential hypertension. This state affects the functions of some organs which can be considered as the targets of the sympathetic influencing. Except for the heart, arterioles, veins and kidneys belong here.
The pathological anatomy of hypertensive disease depends on its course which can be of high quality and malignant. In the first case there are three clinical-morphological stages – the preclinical or transient stage, the stage of widespread changes of arteries, or organic stage, and the stage of the second changes, or organ stage.
The transient (functional) stage clinically occurs as a periodic brief increase of arterial pressure, and morphologically – by the hypertrophy of muscular layer and hyperplasia of elastic structures of arteriole, the spasm of arteriole and moderate compensative hypertrophy of the left ventricle of heart.
The stage of widespread changes of arteries is characterized by constantly increased arterial pressure. Walls of small arteries and arterioles are in a state of proof reduction and hypoxia. Their permeability increases. Plasma enters the structures of vascular walls (plasmorrhagia), and the latter are destroyed. The elements of destruction, and also protein and lipids of plasma are removed through the wall by resorbtion, but as a rule, is incompleted, which results in the development of hyalinosis and arteriolosclerosis. The vascular wall becomes thickened, and the lumen of arteriole becomes narrower.
Atherosclerosis of the renal arteries
In large arteries, unlike the changes of arteriole mentioned above, elastofibrosis develops and atherosclerosis. Elastofibrosis is a compensative process for hypertension as hyperplasia and the ruptureing up of the internal elastic membrane of vascular wall. The development of atherosclerosis is related to the destruction of the vascular wall, accumulation of cholesterol and increased arterial pressure.
The typical clinical-morphological display of this stage is hypertrophy of the left ventricle of heart, and also dystrophy and necrosis of cardiomyocytes.
The stage of the secondary or organ changes is characterized by the destructive, atrophic and sclerotic changes of internal organs. There is diffuse smallfocus cardiosclerosis in the hypertrophied heart, in kidneys arterial sclerotic nephrosclerosis develops or initially wrinkled kidneys which are symmetrically diminished and have a dense consistency, with small tuberositas on the surface and the thickening of the cortical layer on section. Microscopically, the bulge of the afferent arteriole appears which expresses hyalinosis, sclerous and hyalinous, glomerular tubules are obsolete and the stroma is scleroused.
For the malignant clinical course of hypertensive disease such characteristic as frequent hypertensive crisis is present (it is a acute increase of arterial pressure, which occurs as a result of the spasm of arteriole). The morphological sign of crisis is goffering and the destruction of basal membrane, location in endothelium of paling, plasmarrhagia, fibrinoid necrosis of walls of arteriole and thrombosis. Myocardiac infarctions and hemorrhages develop in internal organs.
Cause of myocardial infarction.
Thrombosis of coronary artery, microscopic
Depending on the predominance of structural alteration of vessels in a certain pool and relation to its clinical-morphological changes, there are kidney, cerebral and cardiac clinical-morphological forms of hypertensive disease.
The kidney form of hypertensive disease is characterized by acute and chronic displays. Before acute displays, which removes the main malignant character of the disease, occurs myocardiac infarction, arterionecrosis and capillarnecrosis of the glomerules of kidneys. The latter can cause acute kidney insufficiency. Sometimes arteriole– and capillarnecrosis are transitory (malignant is chronic).
Chronic displays are expressed by the development of the initially wrinkled kidney. Thus the majority of nephrons due to insufficient blood supply become atrophied and scleroused, those are the small areas of microcavities macroscopically. Other nephrons are compensately hypertrophied and appear above the surface of kidneys as grey–red granules. Kidneys become dense, their surface is fine-grained, the cortical layer is thin, and its capsule is taken off with difficulty.
The cerebral form of hypertensive disease forms the basis of cerebro–vascular diseases, and cardiac – togester with the cardiac form of atherosclerosis – ischemic heart diseases.
The causes of death of hypertensive disease can be hemorrhages in the cerebrum, myocardiac infarctions, malignant nephrosclerosis and excavation of aorta.
Ischemic heart diseases name the breach of the heart functions, as a result of absolute or relative insufficiency of coronary blood supply. In connection with large social meaningfulness of this pathology it is selected IHO in independent nosology unit*. Ischemic heart disease is revealed in arrhythmias, ischemic dystrophy of myocardium, myocardial infarction , cardiosclerosis. It occurs mostly in men above 50 years and occupies the first place in invalidisation and death rate of patients with cardio-vascular pathology. Ischemic heart disease pathogenetically is related to atherosclerosis and hypertensive disease and is basically the cardiac form of these diseases having the same risk factors. Other defects of the coronary arteries, in particular at rheumatism, periarteritis nodosa can lead to ischemic heart disease.
Etiology and pathogenesis, risk factors. Direct causes of ischemia of heart are more frequently spasm, thrombosis or embolism of coronal arteries, and also functional overload of the myocardium in the conditions of sclerotic occlusions of these vessels. But these are only local factors of ischemia and necrosis of cardiac muscle. In the origin of ischemic disease as a cardiac form of atherosclerosis and hypertensive disease an important role is played by the following conditions hyperlipidemia, arterial hypertension, obesity,hypodynamia, smoking, diabetes mellitus and gout, chronic emotional overstrain, inherited inclination. At combination for the same person during 10 of such factors, as hyperlipidemia, arterial hypertension, smoking and surplus mass, there will be ischemic heart diseases in the half of cases.
Ischemic heart diseases has undulating motion. In the background there is chronic (relative) insufficiency of coronal blood circulation, there are flashes of acute (absolute) insufficiency. That is why we distinguish the acute and chronic forms of ischemic heart diseases. The acute form shows up ischemic dystrophy of myocardium of –stenocardia (Angina Pectoris) and myocardiac infarction (by necrosis) of myocardium, chronic – cardiosclerosis. The latter is diffuse small– and largfocus and postattack largfocus. Sometimes cardiosclerosis is complicated with chronic aneurysm of heart.
Subendocardial myocardial infarction
It is known that providing of myocardium blood for a healthy man is carried out the system functionally eventual arteries. The diameter of anastomoses between right, middle and left coronal arteries does not exceed 40 mkm, collaterals are not developed. At the time of physical training blood supply of myocardium is provided due to hyperemia of intraorganic branches of coronal vessels. Hyperemia is caused by metabolits that appear during activating of tissue exchange. In addition, metabolic expansion of coronal arteries is combined with the oppression of sensitiveness of a-adrenoreceptors to the vasoconstrictors influencing. Due to these mechanisms the increase of volume speed of coronal blood flowing always answers the growings requirements of myocardium in oxygen.
Patients with the stenous sclerosis of coronal arteries have the continuous piling up of vasoactive metabolits in the focus of ischemia that exists permanent dilatation vessels of microcirculatory river-bed, which diminishes their functional reserve. These vessels are not able to provide the increase of volume speed of coronal blood flowing the physical training. For patients with atherosclerosis even in the conditions of rest there is a deficit of blood supply of myocardium. Morphologically it reminds a mosaic, built of normal cardiomyocytes and cardiomyocytes with changed structure and function (dystrophy and necrosis – in one, hyperplasia – in other places). Clinically it shows up such characteristic as pains and electrocardiography changes, however enzymemia (increase of activity of transaminase, lactatdehydrogenase and other enzymes in blood), which testifies to the presence of myocardiac infarction is absent. This state is called stenocardia (Angina Pectoris). We distinguish its unstable and stable forms.
Morphologically stenocardia (Angina Pectoris) is characterized by ischemic dystrophy of myocardium. It is flabby, in the focus of ischemia, pale and filling out. Histologically we find out paresis of vessels, sometimes fresh blood clots, interstitial is swollen, red corpuscles stasis, the disappearance of transversal banding cardiomyocytes, diapedesis hemorrhages. Electronic – microscopic and histochemical changes are taken to diminish the amount of granules of glycogen, the swelling and destruction of chondriosome and tubules of sarcoplasmatic net. These changes are conditioned by the breach of the tissue breathing, the strengthening of anaerobic glycolysis, breaking up of breathing and oxidizing phosphorilation. In development of destructive changes of cellular organelles an important role is played by disengaged catecholamines and to the changed water-electrolyte exchange (loss of magnesium, potassium and phosphorus but piling up of sodium, calcium and water).
Long durated coronal spasm, thrombosis or occlusion of coronal vessels are causes of the transition of ischemic dystrophy of myocardium at the time of myocardiac infarction. Myocardial infarction is circulatory ischemic necrosis of cardiac muscle that is why, except for the changes of electrocardiogram, enzymemiya is typical for it. Morphologically it is ischemic myocardiac infarction with hemorrhagic crownom. It is classified by the time of origin, by localization, distribution and motion.
Complete necrosis of cardiomyocytes is formed within a day. At first myocardium in the pool of the damaged artery is flabby, unevenly vascularity. Histologically the accumulations of leucocytes appear in capillaries, emigration of them, diapedesis hemorrhages, relaxation of cardiomyocytes, the disappearance in the latter of glycogen and oxide restoration enzymes. During the following hours the outlines of fillings out cardiomyocytes become wrong, transversal banding disappears.
Macroscopically the area of a myocardiac infarction expressly appears only through 18-24 hours after the origin of disease. A necrotic area acquires grey-red color, it is limited by the ribbon of hemorrhage and something comes forward above the surface of section as a result of edema. The phenomenon of edema disappears in subsequent days, necrotic tissue falls back, becomes dense, yellow grey. On periphery a demarcation billow which consists of leucocytes is formed, fibroblasts and Macrophages. The latter take part in resorbtion of dead masses, lipids and tissue detritus accumulate in their cytoplasm. Fibroblasts take part in fibrinogenesis. The process of organization of myocardiac infarction lasts for 7-8 weeks. The connecting tissue germinates from the area of demarcation from the round of the stored tissue in the area of necrosis. Newformed connecting tissue at first is magnificent, as granulation, afterwards passes in rough fibrose. In it and round it islands of hypertrophied cardiomyocytes appear. Investigation of this process is the formation of a dense scar – the morphological basis of postattack largefocus cardiosclerosis.
The acute myocardial infarction has the most frequent complication as cardiogenic shock, fibrillation of ventricles, asystole, acute cardiac insufficiency, Myomalation, acute aneurysm and rupture of heart, parietal thrombosis and pericarditis.
There is melting of myocardium in the cases of predominance of autolisis of dead tissue – Myomalation. Myocardium in these cases is helpless to counteract interventricle pressure of blood. Wall of heart is thickeningand knobs outside, that results in formation of additional cavity – aneurysm of heart. Compensately parietaly blood clot appears in it. It covers the tears of endocardium and strengthens durability of wall. At insufficient thromboformation blood penetrates under endocardium and necrotic tissue what conduces hearts to the rupture. Blood is outpoured in the cavity of cardiac shirt (hemopericardium). Parietal blood clots arise up mainly at transmural and subendocardial myocardiac infarctions. They can be the source of embolism, for example, of kidney vessels.
At subepicardial and transmural myocardiac infarctions there is the reactive exudative inflammation – fibrinous pericarditis often enough
Cardiosclerosis makes the structural basis of chronic ischemic heart diseases. It can be atherosclerotic diffuse smallfocus or can be developed at hypertensive disease, and also postattack largfocus. The first form is related to hypoxia of myocardium. The connective tissue replaces the places of dystrophy, atrophy and dead cardiomyocytes, and also overgrows in perivascular spaces. Macroscopically such cardiosclerosis is presented as white perivascular layers and narrow ribbons in all layers of heart muscle.
The organization of myocardiac infarctions is completed by largefocus cardiosclerosis. Sometimes it is the vast fields of connecting tissue, which take all layer of wall of heart. In such cases it is thinned and knobs under pressure of blood – an aneurismatic sack appears.
At the time of chronic ischemic heart diseases constantly there are terms for development of the repeated myocardial infarction with all characteristic complications.
Cardiogenic shock, fibrillation of ventricles, asystole, acute cardiac insufficiency, come forward in the early period of myocardiac infarction direct causes of death. In the course of time the first place will be taken up by the rupture of heart and thromboembolia of vessels of cerebrum. At the time of chronic ischemic heart diseases death is caused by cardiac insufficiency, thromboembolic complications and rupture of wall of aneurysm.
Cardiomyopathy is an disease with the insufficient retractive function of cardiomyocytes as a result of dystrophic changes of myocardium, which are unconnected with coronal blood circulation or rheumatic defeats.
Classification. Cardiomyopathy is divided into primary (idiopathic): dillatation (congestive), hypertrophy (constrictive, obstructive), restrictive; but the second: intoxication (alcohol, salts of heavy metals, uremia)infectious, exchange inherited (amyloidosis, glycogenosis) and acquired (thireotoxicosis, gout, hyperparathireosis, avitaminosis), alimentary (malabsorption, cirrhosis of liver).
Dillatation cardiomyopathy is characterized by the considerable expansion of cavities of heart, hypertrophy and dystrophy of myocardium and decline of his retractive function. Often occurs after the carried viral infection (Koxaki), drinking of alcohol.
Hypertrophy cardiomyopathy is characterized by the expressed hypertrophy of myocardium as a result of the increased sensitiveness to catecholamines with the disorganization of Myofibrils and the diminishing of volume of cavities of heart.
Restrictive cardiomyopathy is characterized by the rigidity of walls of the ventricles of heart, which develops as a result of endoMyocardial fibrosis, fibroelastosis, fibroplastic eozinofil endocarditis. The cavities of ventricles can even be diminished, and the cavities of atriums broaden.
The second cardiomyopathy is characterized by the development of dystrophic changes in cardiomyocytes as a result of action of that or other etiologic factors that is why their displays can differ.
Complications of cardiomyopathies can be: sudden death, thromboembolic syndrome, chronic cardiac insufficiency.
Vasculitis is an inflammatory disease of vessels which is often accompanied by destructive changes in a wall.
Classification. We can distinguish local and system vasculitis. Depending on localization there are aortitis, arteritisis, arteriolitis, capillaritis, phlebitis. In addition, vasculitis can be endo-, mezo-, peri-, panvasculitis. Also, the infectious and immunodefensive vasculitis are distinguished.
Systemic vasculitis is revealed in different types of inflammatory reactions: alterative-exudative, productive, necrotic, destructively productive and granulematous. In the pathogenesis of the development of the morphological changes the basic process is the immune reactions of hypersensitivity.
Types: primary vasculitis:
– the vasculitis of aorta and its large branches by granulematous gigantcellular reaction (unspecific aortoarteritis or Takayasu arteritis, temporal arteritis or Horton’s arteritis);
– the vasculitis of the middle and small arteries with destructive productive reaction (periarteritis nodosa, allergic granulomatosis, systemic necrotic vasculitis, Wegener granulomatosis );
– the vasculitis of arteries of small caliber, capillaries, veins (thromboangitis obliterans or disease of Buerger);
secondary vasculitis:
– infectious (syphilis, tuberculosis, ricket, sepsis);
– the systemic diseases of connective tissue;
– the vasculitis of hypersensitiveness (serum sickness, malignant new formations).
Unspecific aortoarteritis (arteritis of Takayasu) or arteritis of young women appears as the productive granulematous inflammation in the wall of aorta, the cause of which can be different factors. The bulge of wall, the formation of aneurysm, parietal blood clots, the deformation of aorta is developed.
Periarteritis nodosa (disease of Kussmaulya-Mayera) is characterized by the development of necrotic imunnocomplex vasculitis in the arteries of middle and small sizes of every localization, but more frequent in kidneys, heart, the digestive system, the nervous system and skeletal muscles. The necrosis of media and intima with infiltration of the walls by lymphocytes, plasmatic cells and eosinophils are typical. Aneurysm of vessels, hemorrhages, thrombus and blood clots develop. In kidneys, immunocomplex arteriolitis and glomerulonephritis develop. Kidney failure and arterial hypertension are often the causes of death at periarteritis nodosa. The damage of coronary arteries predetermines the development of ischemic damage of myocardium. In the organs of the digestive system there are ischemic damages of guts at periarteritis nodosa, gangrene can also develop sometimes. There are myalgias in the skeletal muscles, artralgias and arthritis. Aneurysm which can be ruptured and can cause the fatal bleeding or insults of cerebrum develop in the vessels of cerebrum.
Wegener granulomatosis is the necrotizing of vessels of mainly the upper respiratory tracts, kidneys and other organs with the development of alterative, exudative and productive (granulematosis) inflammatory changes. Complication is hyalinosis, sclerosis, the formation of aneurysm in the wall of vessels and sclerosis and the deformation of organ. Mesangiocapillar glomerulonephritis often develops.
Thromboangitis obliterans (disease of Winiwarter -Buerger) is a productive inflammation of mainly small arteries and veins of lower limbs with the development of blood clots, the obliteration of vessels and gangrene of extremity. Microabscesses can develop with necrotic changes in tissues. More frequently it occurs in men who smoke.
Defects of heart are proof rejections in its structure and predetermine the breach of function. We distinguish the acquired and born defects.
The acquired defects develop as a complication of rheumatism, atherosclerosis, syphilis, bacterial endocarditis. The eventual link of pathogenesis of the acquired defects of heart is the sclerotic deformation of valves in connection with the chronic inflammation and the disorganization of connecting tissue. Hereupon there is the insufficiency of valve (it is not closed up fully) or its stenosis, more frequent there is the combined defect – the combination of stenosis and the insufficiency of that valve. After localization we distinguish the defects of mitral, aortic, three-leaved valves and valves of pulmonary artery. The acquired defects can be compensated and decompensated. The signs of general venous plethora develop at decompesated defects, that is morphological picture of chronic cardiac insufficiency which is often the cause of death of such patients.
Born defects of heart depending on the degree of hypoxia can be cyanotic and white. At dark blue defects circulation of blood is carried out by anomalous ways from right to left (general arterial barrel, complete transposition of pulmonary artery and aorta, stenosis and atresia of pulmonary artery or aorta, combined defects of Fallo). Blood flows around the small circle of blood supply or passes through it only partly. At the time of white defects hypoxia is absent. Blood circulation of is carried out from left to right. Depending on the breach of morphogenesis of heart all of defects are divided into three groups:
– Defects with the breach of the division of cavities of heart: partial or complete defect of interventricles partition, isolated defect of interatrial partition (wide oval opening). These are white defects; the three-chambered heart is often formed;
– Defects with the breach of the division of general arterial barrel: complete absence of division, transposition of pulmonary artery and aorta: aorta flows away from the right ventricle, and pulmonary artery from the left ventricle behind aorta;
– combined defects: triad (defect of interventricle membrane, stenosis of pulmonary artery and hypertrophy of right ventricle), (defect of interventricle membrane, stenosis of pulmonary artery, dextraposition of aorta and hypertrophy of right ventricle), (defect of interventricle membrane, stenosis of pulmonary artery, dextrapoition of aorta and hypertrophy of right ventricle, defect of interatrial membrane) of Fallo.
Myocarditis is a group of diseases which is characterized by the inflammation of cardiac muscle. According to etiology we select primary and secondary myocarditis. More frequent are secondary myocarditis: – infectious (viral, bacterial, mycotic and), infectiously allergic (at rheumatic diseases, gigantcellular arteriitis, Wegener granulomatosis , generalized sarkoidosis), toxic (uremia, diphtherial toxin, substances of phosphorus), medical.
Gigantcellular idiopathic myocarditis of Abramov- Fiedler is shown up by the focus of necrosis of cardiomyocytes, by diffuse inflammatory infiltration of myocardium with lymphocytes, eozinofils, plasmatic cells, giant cells and ends with cardiosclerosis.
Autoimmune Systemic Diseases of Connective Tissue . Rheumatism. Rheumatoid Arthritis. Systemic Lupus Erythematosus. Scleroderma. Dermatomyositis. Bechterew’s (Strumpell’s) disease
Rheumatic Diseases
Rheumatic diseases are a group of chronic diseases characterized by systemic lesion of connective tissue and blood vessels. In their etiology a significant role is played by a clinically apparent or latent streptococcic infection and the pathogenetic mechanisms mainly consist of allergic reactions of delayed and immediate type. There develops a progressive disorganization of connective tissue – a mucous edema, a fibrinoid edema and necrosis, cellular reaction (granulomatosis) and sclerosis.
Although the pathogenesis of rheumatic diseases is of a single-type, every nosologic form has its characteristic peculiarities. In rheumatism, for instance, the sensitizing factor is the antibodies against the β-hemolytic streptococcus of A-type that have affinity to antigens of cardiac connective tissue. That is why rheumatism usually affects the patient’s heart.
Rheumatoid arthritis mainly affects the connective tissue of articular capsules. The immune complexes where the antibodies are immunoglobulins of various types (Ig M, Ig G, Ig A) are important for the pathogenesis of the disease.
In systemic lupus erythematosus the DNA metabolism is disturbed and antibodies are produced against the components of the nucleus and the cytoplasm – DNA, RNA and nucleoproteins. This causes polymorphic changes in many organs and tissues but mainly in skin, vessels, kidneys and heart.
Visceral Manifestations of Rheumatic Diseases
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Rheumatism |
Arteritis, arteriolitis, capillaritis, endocarditis, myocarditis, pericarditis, serofibrinous polyarthritis, glomerulonephritis, erythema nodosum of skin, polyserositis, chorea minor, pneumonia, hypodermic nodes |
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Rheumatoid arthritis |
Arteritis, arteriolitis, progressive destructive polyarthritis, fibrous and bony anchylosis, osteoporosis, polyserositis, glomerulonephritis, pyelonephritis, renal amyloidosis, cardiosclerosis |
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Systemic lupus erythematosus |
Arteriolitis, capillaritis, vasculitis, intermediate inflammation of internal organs followed by sclerosis, periarterial bulbous spleen sclerosis, hyperproduction of immunoglobulins, DNA loss, appearance of lupous cells, erythema of skin (butterfly circuit), Libman-Sacks endocarditis, glomerulonephritis, polyarthritis without articular deformations |
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Scleroderma |
Arteriolitis, capillaritis, sclerosis, hyalinosis, skin atrophy (parchment-skin), sclerodermic heart (macrofocal cardiosclerosis), sclerodermic kidney (cortical necrosis), basal pneumofibrosis |
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Periarteritis nodes |
Vasculitis (destructive, destructive-and-productive, productive), infarcts and postinfarction sclerosis of internal organs, haemorrhage, glomerulonephritis |
Systemic scleroderma is characterized by sclerotic and atrophic changes of skin. Deranged synthesis of collagen is considered to be the decisive factor for scleroderma development.
Periarteritis nodosa is defined by a complex immune mechanism of arterial lesion of small and medium calibre which leads to secondary transformations of internal organs. It is considered that the fibrinoid necrosis of middle layer of blood vessels causes the development of proliferative reaction of cells in the external layer, which is followed by sclerosis and formation of nodes.
The group of rheumatic diseases is constantly growing owing to new nosologic forms included into it, whose pathogenesis is connected with systemic disorganization of connective tissue and blood vessels. Bechterew’s disease and dermatomyositis fall into this category. Bechterew’s disease is a chronic rheumatic disease consisting of lesion of articular-and-ligamentous apparatus of the spine that leads to bony anchylosis. Dermatomyositis is a rheumatic disease that manifests itself mainly in systemic lesion of transversely striated muscles and less in that of non-striated muscles.
Rheumatism is a chronic disease with prevailing lesion of heart and blood vessels. Its progression is undulating, periods of exacerbation alternating with remissions. Its development is associated with β-hemolytic streptococcus of A-type. However, rheumatism cannot be regarded as a simple streptococcic infection. Penetrating the body through the tonsils, streptococci releases toxins and causes cell destruction and inflammation in the places of invasion that usually manifests as tonsillitis. The toxins and cell destruction products are the antigens against which antibodies are produced. Recurrent exacerbation of tonsillitis serves as a starting point of the development of the disease.
It has been proven that some streptococcic products break up glucosamine-and-protein complexes in the connective tissue. As a result of immune response to streptococcic components and tissue destruction products, a wide range of antibodies and immune complexes appears in the blood which creates preconditions for autoimmune processes.
Four stages of connective tissue disorganization are observed in the development of rheumatism – mucous edema, fibrinoid changes, granulomatosis and sclerosis. Mucous edema is a surface and reverse disorganization of connective tissue characterized by intensified metachromatic reaction to glucosaminoglycanes and hydration of basal substance. For a clinician it is important to know that this phase is reversible. Early diagnosis and beginning of treatment may bring about complete recovery.
Fibrinoid changes (swelling and necrosis) are irreversible. They are characterized by homogenization of collagen fibres that get filled with plasma proteins, including fibrin.
The stage of granulomatosis manifests itself morphologically in inflammatory reaction of cells. It was first described in the form of nodular masses in heart stroma by Aschoff (1904) and in 1930 V.Talalayev singled out three phases in the development of rheumatic granuloma – alterative-exudative, proliferative and sclerotic. Correlating them to clinical data he showed that the whole cycle of granuloma development lasts for 4-6 months.
The alterative-exudative phase is characterized by accumulation of macrophages around the fibrinoid necrosis focus, which transform into large cells with a hyperchromic nucleus. Such granuloma is called (“floriferous”). It indicates an acute process going on.
During the proliferative phase the cells become elongated, fibroblasts appear and the quantity of fibrinoid masses decreases. The “fading granuloma” develops. This indicates the attenuation of the process.
In the phase of sclerosis the fibroblasts substitute the fibrinoid necrosis zone, and reticular connective tissue fibres and collagen fibres are synthesized. The granuloma assumes the properties of a scar. This indicates the remission of the disease.
In typical progression of rheumatism the heart is affected first and foremost. Endocarditis, myocarditis, and less often – pericarditis develop there. Sometimes one can observe acute polyarthritis characterized by swelling of big joints, quick passage from one joint to another, and restoration of their functions during remission. Chorea, erythema annulare, formation of hypodermic nodes that used to be typical of rheumatism, is relatively rare nowadays.
According to localization, endocarditis can be valvular (valvulitis), chordal and parietal. In most cases the rheumatic process affects the mitral and the aortic valves. Depending upon the prevailing alterative or regenerative process, one can distinguish four types of rheumatic valvular endocarditis:
a) diffuse endocarditis characterized by diffuse mucous edema of connective tissue without endothelium lesion;
b) acute verrucous endocarditis defined by fibrinoid transformation of connective tissue and endothelium desquamation with accumulation of thrombotic masses in the form of warts in the places of lesion;
c) fibroplastic endocarditis that develops as a result of the above mentioned forms and is characterized by excrescence of the newly formed connective tissue, emboli of blood vessels and regeneration of epithelium; the valve is thickened and transformed by scars which causes its deficiency (acquired valvular disease);
d) recurrent verrucous endocarditis characterized by recurrent disorganization of the newly formed connective tissue, endothelium lesion and fibrin deposition due to sclerosis and hyalinosis of the valve; this process indicates a recurrent rheumatism attack.
Myocarditis is a constant manifestation of rheumatism. Three forms of it are singled out:
a) granulomatous, characterized by the presence of “floriferous”, “fading” and sclerotic rheumatic granulomas in perivascular connective tissue;
b) diffuse exudative interstitial myocarditis characterized by edema, hyperaemia and considerable infiltration of interstitium with lymphocytes, histiocytes, neutrophils and eosinophils, and solitary Aschoff-Talalayev granulomas;
Here is an Aschoff nodule at high magnification. The most characteristic component is the Aschoff giant cell. Several appear here as large cells with two or more nuclei that have prominent nucleoli. Scattered inflammatory cells accompany them and can be mononuclears or occasionally neutrophils.
c) focal exudative interstitial myocarditis that manifests itself in slight focal infiltration of interstitium with lymphocytes, histiocytes and neutrophils. Under favourable conditions myocardite develops into cardiosclerosis.
Pericarditis is a sort of serous, serofibrinous or fibrinous exudative inflammation. It often ends with the formation of adhesions. Obliteration of pericardial cavity and calcification of the formed connective tissue may also occur (stone heart).
The combination of endo- and myocarditis is referred to as rheumatic carditis, and that of endo-, myo- and pericarditis – as rheumatic pancarditis.
Vasculitis in of rheumatism is of systemic nature and is observed in all organs and tissues. Capillary permeability increases drastically, clinically manifests itself as nodular erythema. Often skin capillaries are wrapped in pericyte muffs and endothelium is in the state of proliferation. Eventually sclerosis develops around capillaries with the formation of rheumatic nodes.
Polyarthritis is usually of serofibrinous type in rheumatism. Articular cartilage is not damaged so there is articular deformation.
Chorea minor is a cerebral form of rheumatism. It occurs more often in children. Because of vasculitis dystrophic changes of nerve cells develop in the brain as well as destruction foci and haemorrhages that are the morphologic basis of clinical presentations.
Rheumatism complications are connected in most cases with heart lesions;valvular defects and embolisms in verrucous endocarditis, internal infarcts, encephalomalacia, limb gangrene, commissures and obliteration of pericardial cavity.
The most frequent cause of death of rheumatism is decompensated valvular defect and thromboembolic complications.
Rheumatoid arthritis is a chronic disease based on progressive disorganization of connective tissue of synovial membranes and articular cartilages. Its characteristic feature is the development of nonsuppurative proliferative synovitis followed by articular deformations. It often causes damage of the skin, blood vessels, heart, lungs, muscles and other organs and tissues. It affects mainly women. The disease is of unknown etiology, but there is genetic susceptibility to autoimmune reactions to collagen of Type 2. For that matter T-lymphocytes therefore release inflammatory mediators and lytic cytokines that destroy joints. Microbial infection, especially viruses, is often the starting point for the disease. The body produces antibodies to its own Ig G, which is the rheumatoid factor.
Morphologic changes mainly manifest themselves in the lesion of musculoskeletal system. Synovitis of three stages develops. The first stage is characterized by edema of the synovial membrane and villi with the development of disorganization of connective tissue: mucoid and fibrinoid intumescence, fibrinoid necrosis. The villi necrotize and there develops “rice body”. There are signs of inflammatory reaction of cells in tissues. The second stage manifests itself in the growth of villi and proliferation of synoviocytes, inflammatory cellular infiltration, formation of granulation tissue on the joint surface, erosions in articular cartilage, exposure of bone and epiphyses, and in osteoporosis. The granulation tissue narrows the joint space, decreases articular mobility and causes dislocations and subdislocations. The third stage manifests itself in fibrous and bony anchylosis and develops after long progression of the disease. It is defined by complete articular immobility, the formation of rheumatoid nodes around joints with signs of destructive changes in connective tissue.
The main visceral manifestations of rheumatoid arthritis are polyserositis, vasculitis in the lungs and heart with disorganization of connective tissue and inflammatory cellular infiltration with lymphocytes, plasmocytes and histiocytes. The heart may be affected by endocarditis with the development of valvular disease and the lungs – by pneumosclerosis.
One of the complications is renal amyloidosis with the development of uraemia which is often the cause of patient’s death.
Bechterew’s (Strumpell’s) disease (poker back) or spondylitis anchylosis, rheumatoid spondylitis is a chronic rheumatic disease characterized by the lesion of articular-and-ligamentous apparatus of spine that ends with its immobility. In its etiology and pathogenesis the main role is played by infectious and allergic factors, spinal trauma and heredity. More often it affects men. The pathologic anatomy is characterized by the development of destructive-inflammatory changes in the tissues of small spinal joints with the destruction of articular cartilage and the development of bony anchylosis. Similar transformations develop in intervertebral disks. The spine becomes completely immobile. It also damages internal organs: aorta, heart, lungs. Renal amyloidosis also develops, which is often the cause of death.
Systemic lupus erythematosus (SLE) (Libman-Sacks disease) is a systemic disease marked by autoimmunization that has acute or chronic progression and is characterized by the lesion of skin, vessels and kidneys. More often it affects young women. The cause of the disease is unknown. A nonspecific provoking factor is ultraviolet radiation and pregnancy. The disease may also develop after a viral infection. Hereditary factors also play an important role. In its pathogenesis a significant role is played by the imbalance of the function of T-suppressors and T-helpers with the formation of multiple organ antibodies (lupous factor – antinuclear antibodies). The pathologic anatomy is characterized by the development of fibrinoid changes in the walls of microcirculation vessels with the formation of vasculitis that ends with secondary ischemic changes in organs in the form of dystrophy and necrosis. The skin is affected by cheek erythema – “red butterfly” – due to proliferative-destructive vasculitis in the derma; edema and focal perivascular lymphohistiocytic infiltration. Kidneys are affected by lupous glomerulonephritis or mesangial proliferative glomerulonephritis. A characteristic peculiarity is the deposition of immune complexes and capillary thickening in the form of “wire loops”, fibrinoid necrosis foci, hematoxylin bodies, hyaline thrombi. Glomerulonephritis results in contraction of kidneys and the development of renal insufficiency which is often the cause of patient’s death. The patient’s heart is affected by nonbacterial verrucous Libman-Sacks endocarditis where hematoxylin bodies can be found in the necrosis foci. In contrast to rheumatism no mucoid or fibrinoid intumescence can be observed. In spleen one can find periarterial “bulbous sclerosis”. Among complications of SLE and causes of death are lupous nephritis and the development of renal insufficiency.
Systemic scleroderma (systemic sclerosis) is defined by the development of diffuse sclerosis and hyalinosis of connective tissue in various organs and tissues. The etiology and pathogenesis is unknown. Important for the disease development are viral infections and hereditary factors with autoimmunization. Pathologic anatomy. Major changes develop in the heart, kidneys, gastrointestinal tract, blood vessels and skin. In the heart there is sclerosis and contraction of mitral valve cusps, subendocardial cardiosclerosis with the development of cardiovascular collapse – “sclerodermic heart”. In coronary vessels one can often find concentric sclerosis and hyalinosis. Around vessels there is inflammatory infiltration with lymphocytes, macrophages and plasmatic cells. The skin is affected by diffuse or focal epidermal atrophy, sclerotic transformations and hyalinosis of connective tissue. In dermal vessels one can observe vasculitis and later reduction of bloodstream. Due to insufficient vascularization there appears necrosis and exulceration foci in the skin. The latter becomes dense, with foci of hyperpigmentation and hemangiectasia. The face becomes masklike. In the kidneys there develops progressive vasculitis, concentric thickening and thrombosis of interlobular arteries, cortical necroses and infarcts, parenchyma sclerosis with the development of renal insufficiency. In the lungs one can observe carnification due to diffuse fibrosis, thickening of alveolar septa, arteriolosclerosis. In the gastrointestinal tract one can observe sclerotic transformations of submucous and muscular layer, swallowing and absorption disturbance, slowing-down of motility and development of cachexy.
Dermatomyositis is characterized by the lesion of transversely striated muscles and less by that of non-striated muscles. More often it affects skeletal, pharyngeal, laryngeal, ocular and diaphragmatic muscles. Muscles undergo atrophic and dystrophic changes, lose their striation, their fermentative activity and glycogen supplies decrease and sometimes coagulatioecrosis occurs. Muscles are gradually substituted by connective tissue and fat masses. In the heart one can observe dystrophy of cardiomyocytes, intermediate myocarditis with productive vasculitis, edema of intercellular substance, and infiltration with lymphocytes, macrophages and plasmatic cells. The process ends with diffuse cardiosclerosis and atrophy of cardiomyocytes. In the lungs, alveolar septa are thickened. In the gastrointestinal tract one can observe atrophic and dystrophic transformations of muscular cells, perivascular lymphomacrophage infiltrations, sclerosis of mucous and submucous layer. Other organs undergo inflammatory and sclerotic changes.
The diseases of respiratory organs
Pneumonia is a disease, which by etiology, pathogenesis and morphological description unites the large group of various diseases of inflammations of respiratory compartment of the lungs. There are three ways of entrance of stimulants of pneumonia into the lungs – bronchogenic, hematogenic and lymphogenic. The first of them has a leading value. At first an inflammatory process occurs in the bronchiole, and then spreads to the parenchyma of the lungs (bronchopneumonia). If inflammation has mostly productively exudative character, it passes on to the interalveolar septa, known as interstitial pneumonia. Next to it, there is an independent infectious disease, which shows up in that among a complete health sharply catches a fire fibrinous inflammation of parenchyma of lungs is parenchymatos (lobar pneumonia) pneumonia.
Lobar pneumonia – in 95 % of cases is caused by s Fraenkel’s pneumococcus, or rarer by Friedländer’s diplobacillus, by streptococcus, staphylococcus, and Pfeiffer’s bacillus. A cold which decreases the immunobiological reactivity acts as a provoking factor. Disease often arises in persons with alcoholism, avitaminosis, cardiac insufficiency, and chronic overstrain. Morphological changes in lobar pneumonia occur in a certain sequence, which distinguishes a few stages of the process (К.Rokitansky) – stage of congestion (from 12 hours to 3 days), stage of red hepatization (1-3 days), stage of grey hepatization (2-6 days), and stage of resolution.
Pneumonia begins with a small of inflammation in the posterior or postero-lateral segments of the lungs round the colonies of pneumococcus. Inflammation spreads by contact and quickly absorbs one or few pulmonary substance. In the stage of congestion, the lung is megascopic in volume, with exudates in its tissue and is sanguineous. In the stage of red hepatization, the exudate is enriched with fibrin and red corpuscles. The lungs, under close view look the liver, and is crimson coloured on section. The color of the phlegm is rusty. On the 4-6th day, the composition of the exudate changes – red corpuscles disappear, but the number of neutrophils which phagocyte the pneumococcus increases. The surface of the lungs is grey color on section (stage of grey grained detritus it is possible to find remains of fibrins hepatization). During the period of convalescence exudate resolves.
The cut surface of this lung demonstrates the typical appearance of a bronchopneumonia with areas of tan-yellow consolidation. Remaining lung is dark red because of marked pulmonary congestion. Bronchopneumonia (lobular pneumonia) is characterized by patchy areas of pulmonary consolidation. These areas become almost confluent in the left lower lobe on the bottom left of the photograph.The areas of consolidation are firmer than the surrounding lung.
Here is another example of a bronchopneumonia. The lighter areas that appear to be raised on cut surface from the surrounding lung are the areas of consolidation of the lung
At higher magnification, the pattern of patchy distribution of a bronchopneumonia is seen. The consolidated areas here very closely match the pattern of lung lobules (hence the term “lobular” pneumonia).A bronchopneumonia is classically a “hospital acquired” pneumonia seen in persons already ill from another disease process. Typical bacterial organisms include: Staphylococcus aureus, Klebsiella, E. coli, Pseudomonas.
This bronchopneumonia is more subtle, but there are areas of lighter tan consolidation. The hilum is seen at the lower right with radiating pulmonary arteries and bronchi.Many bronchopneumonias follow an earlier viral pneumonia, particularly in older persons in the winter months when influenza is more common.
This is a lobar pneumonia in which consolidation of the entire left upper lobe has occurred. This pattern is much less common than the bronchopneumonia pattern. In part, this is due to the fact that most lobar pneumonias are due to Streptococcus pneumoniae (pneumococcus) and for decades, these have responded well to penicillin therapy so that advanced, severe cases are not seen as frequently. However, pneumoccoci, like most other bacteria, are developing more resistance to antibiotics. Severe pneumococcal pneumonia still occurs, even in young to middle aged persons (not just the very young and the very old) and has a mortality rate of 20%!
Complications of lobar pneumonia are divided into pulmonary and extrapulmonary. The first group consists of carnification, empyema of the pleura, abscess formation, and gangrene. Extrapulmonary complications are pneumococcal inflammatory processes in different organs (lymphadenitis, meningitis, peritonitis, arthritis, etc.). The term “ bronchopneumonia” unites different primary inflammations of the lungs with localization of primary process in bronchial tubes. From here inflammation spreads to the pulmonary tissue and can be limited to the acini, by a particle, segment or particle. Bronchopneumonia occurs more frequently, than lobar. As children and people have an independent disease for years. Bronchopneumonia is complicated by acute respiratory and viral diseases (flu, measles). It can occur at insufficiency of circulation of blood, especially on a background of the stagnant pneumonia in lungs (stagnant pneumonia), at the protracted confinement to bed for heavy and weakened patients (hypostatic pneumonia), and in postoperation period.
In most cases, the cause of bronchopneumonia is aerogenic infection, but hematogenic and lymphogenic ways of transmission are also possible. The process begins in the bronchiole and spreads to the alveolar sacs. Bronchitis can be accompanied by peribronchitis. From peribronchial tissue infection spreads to the nearby alveolar tree (peribronchial pneumonia). Inflammation of alveolar tissue quite often is preceded by the collapse of alveolar passages. It could be a consequence of compression from outside or obstruction of the bronchial tube with exudates followed by suction of air from the alveolar ways which have lost connection with the respiratory passages.
A closer view of the lobar pneumonia demonstrates the distinct difference between the upper lobe and the consolidated lower lobe. Radiographically, areas of consolidation appear as infiltrates.
The pleural surface at the lower left demonstrates areas of yellow-tan purulent exudate. Pneumonia may be complicated by a pleuritis. Initially, there may just be an effusion into the pleural space. There may also be a fibrinous pleuritis. However, bacterial infections of lung can spread to the pleura to produce a purulent pleuritis. A collection of pus in the pleural space is known as empyema.
Atelectasis is an active slump of the pulmonary tissue, which can occur due to shortage of surfactant, while collapse is a passive slump under pressure of exudate, air or tumor. The exception of part of alveolar ways from a respiratory function causes the development of vicarious (compensate) emphysema. Exudate at bronchopneumonia is composed of serous liquid with the admixture of leucocytes, desquamated cells of the alveolar epithelium, red corpuscles, and at times fibrin. That is why serous, purulent, desquamation, hemorrhagic and fibrinous pneumonia are distinguished.
Macroscopically, there are inflammatory focuses which correspond to the collapsed bronchial tubes or particles which appear in lungs. They burst above the surface of cut, have yellow grey, grey or red color, are dense by touch, and sink in water. A turbid liquid which does not contain the blisters of air flows down during their squeezing. From the bronchiole, mucus-purulent exudate is pressed out.
Seen here are two lung abscesses, one in the upper lobe and one in the lower lobe of this left lung. An abscess is a complication of severe pneumonia, most typically from virulent organisms such as S. aureus. Abscesses are complications of aspiration, where they appear more frequently in the right posterior lung.
Seen here are lung abscesses grossly in which the purulent exudate has drained following sectioning to reveal the abscess cavities. Abscesses can be a source for septicemia and are difficult to treat.
Bronchopneumonia mostly ends with convalescence, but complications – gangrene of lungs and carnification are possible. Interstitial (intermediate) pneumonia spreads mainly on intermediate tissue, in lumen of alveolar ways.
This is an abscessing bronchopneumonia in which several abscesses with irregular, rough-surfaced walls are seen within areas of tan consolidation. Lung abscesses, if large enough, will contain liquefied necrotic material and purulent exudate that often results in an air-fluid level by chest radiograph in the abscess
Intermediate pneumonia belongs to the atypical forms. It occurs in viral infections and lobar pneumonia. The process begins with bronchitis and spreads by lymphatic ways (lymphangitis) or hematogenously (system red lupus). Productive inflammation prevails at times (measles). Frequently is purulent lymphangitis. Distinguished types are peribronchial, interlobular and interalveolar pneumonia. Macroscopically, yellow ribbons which separate particles from induration are seen. Sometimes at purulent inflammation, the intervals of **sequestrum** and particles become separated. Such pneumonia supports the development of interstitial emphysema. Complications are abscess formation, empyema and mediastinitis.
Pneumonia of children has some features:
a) Inflammatory process develops mainly in the respiratory parts of lungs;
b) Infection occurs intrauterine or through aspiration of amniotic waters;
c) Hyaline membranes appear as a result of increased permeability of blood vessels;
d) infection is more frequent than in adults and spreads outside lungs – to kidneys, liver, cerebrum.
Bronchitis is divided into acute and chronic bronchitis (bronchitis acuta, bronchitis chronica). Among the etiologic factors of the acute inflammation of bronchial tubes, of important are viruses and bacteria which cause respiratory diseases. Among physical factors are the pathogenic action of dry or cold air, dust; and chemical factors are inhalation of tobacco smoke, steams of chlorine, oxides of nitrogen etc. The inherited impairment of barrier mechanisms of mucus, insufficiency of cellular and humoral (IGA) protective factors of local importance supports the development of bronchitis. In reply to the pathogenic influence on the gland and goblet cells of mucus membrane of bronchial tubes, production of mucus increases. It results in shedding of ciliary the prismatic epithelium, baring of mucus and penetration of infection through the wall of bronchial tube.
At the left the alveoli are filled with a neutrophilic exudate that corresponds to the areas of consolidation seen grossly with the bronchopneumonia. This contrasts with the aerated lung on the right of this photomicrograph.
Acute bronchitis can be of independent nosology or the secondary sign of a series of other diseases (lobar pneumonia, uremia and so on). In the mucus membrane of the bronchial tubes almost all forms of catarrhal inflammation are developed – serous, purulent, fibrinous, fibrinous-hemorrhagic, and mucus. Destruction of the mucus membrane is sometimes possible with the development of ulcers. In such cases it is known as destructively ulcerous bronchitis. Predominance of this or other forms of catarrh depends on the pathogenic factor and resistance of the organism. Inflammation begins from the mucus membrane (endobronchitis), then spreads to the muscular layer (endomesobronchitis) and in the terminal phase affects all the layers (panbronchitis). Certainly, an inflammatory process can be stopped at the development on a certain layer.
Existing of acute bronchitis can be complicated with bronchopneumonia or peribronchial by intermediate pneumonia. Bronchopneumonia is mostly as a result of aspiration of infected mucus in the respiratory compartment of the lungs. Peribronchial intermediate pneumonia occurs as a result of transition of inflammatioot only on peribronchial but also on interstitial tissue.
Serous and mucus catarrh quickly ends with convalescence. Purulent, fibrinous and fibrinous-hemorrhagic catarrh, and also an ulcerous-destructive bronchitis have the protracted course and often progresses to the chronic form or pneumonia.
Chronic inflammation of bronchial tubes is revealed in the following forms:
а) Chronic mucus or purulent catarrh with atrophy of mucus membrane, by the cystous regeneration of glands and metaplasia of prismatic epithelium into stratified squamous epithelium;
b) Chronic productive inflammation is with formation of polyposis from granulation tissue (polyposis chronic bronchitis);
c) deformation of bronchial tube at maturation of granulation tissue, outgrowth of connective tissue in a muscular layer, sclerosis and atrophy of mucus (deforming chronic bronchitis).
Chronic bronchitis with the protracted course, except sclerotic changes, is accompanied by dystrophy of elastic, muscular and cartilaginous frameworks. That is why during cough, when intrabronchial pressure increases sharply, in the areas of the least resistance the wall of bronchial tube broadens and bursts. So, saccular bronchiectasis appear. At diffuse expansion of the bronchial tubes, they have a cylindrical form. Chronic bronchitis is always accompanied by the impairment of drainage function of bronchial tubes, which causes an increase in the period of timemucus spends in the lower parts, closing of airways of bronchiole and the development of bronchiolung complications (obstructive emphysema, chronic pneumonia, pneumofibrosis).
At higher magnification can be seen a patchy area of alveoli that are filled with inflammatory cells. The alveolar structure is still maintained, which is why a pneumonia often resolves with minimal residual destruction or damage to the lung.
Bronchiectasis is inherited and acquired expansions of bronchial tubes in cylindrical or saccular forms. Inherited bronchiectasis occurs in connection with impairment of formation of the bronchial tree. They are marked with the chaotic location of structures of walls of bronchial tubes. Sometimes bronchioles are closed blindly in the parenchyma of lungs and cysts appear. In such cases, it known as cystous lung. Bronchiectasis is acquired with relation to the acute bronchitis, pneumonia, and collapse of lungs.
According to the form of expansion of bronchial tubes, saccade bronchiectasis (local thrusting out of wall) and cylinder bronchiectasis (diffuse expansion of airways of bronchial tube) are distinguished. Expansions of shallow bronchial tubes are known as bronchioloectasis. Lungs in such cases have a cellulous kind (pulmo сisticus).
At bronchiectasis there are the phenomena of chronic inflammation in the wall of bronchial tubes, metaplasia of prismatic epithelium into stratified squamous, dystrophic changes of elastic fibres, cartilaginous tissue and leiomyocyte and sclerosis. In the cavities of bronchiectasis mucus and purulent exudates accumulate. Based on this, abscesses, perifocal purulent pneumonia, perifocal fibrous, obstructive emphysema occur. Sclerosis develops in vessels in the presence of plural bronchiectasis and emphysema results in the development of hypertension in the lesser blood circulation and hypertrophy of the right ventricle of the heart. The symptoms of hypoxia appear with the disorder of trophism of tissues that follows. A very typical sign is the bulging of the distal phalanges of fingers and toes as “drumsticks”.
A combination of changes in the lungs and complications (pulmonary heart, general amyloidosis, hypoxic signs, sclerosis, etc.) at presence of bronchiectasis examined as new nosology is bronchiectatic disease.
At high magnification, the alveolar exudate of mainly neutrophils is seen. The surrounding alveolar walls have capillaries that are dilated and filled with RBC’s. Such an exudative process is typical for bacterial infection. This exudate gives rise to the productive cough of purulent yellow sputum seen with bacterial pneumonias.
Emphysema of lungs is the pathological state of the pulmonary tissue, characterized by the increased presence of air in it. Vesicular, diffuse obstructive, chronic, focus, compensating, primary panacinar, senile and interstitial types of emphysemas are distinguished. Development of vesicular emphysema is related to chronic bronchitis, bronchiolitis and by their consequences – plural bronchiectasis. It has been discovered, that there is a deficit of inhibitors of protease – elastase, collagenase in these diseases. Insufficiency of the important inhibitor; )1–antitrypsin can be genetically conditioned. Activation of elastase and collagenase causes the destruction of interalveolar septa leading to bigger cavities.
Diffuse obstructive emphysema (emphysema pulmonum obstructium diffusum chronicum) occurs at chronic diffuse bronchitis. Its development is by valvular mechanism. It happens because air accumulates in the alveolar ways during inhalation and remains even after exhalation due to the presence of mucus clots in shallow bronchial tubes and bronchioles. Air is accumulated in the acinus, which becomes broadened as a result of the deficiency of elastic and collagen fibres. Huge dilation of the respiratory bronchiole and acinus result in centriacinar emphysema, while dilation of the large bronchial tubes and acinus result in panacinar emphysema. Stretching of walls of acinus results in thinning of interalveolar septa, expansion of interalveolar sac and formation of vesicular blisters. The capillary net of partitions empties. Thus, there is the considerable diminishing of the area of gaseous exchange and a ventilatory function of lungs is impaired. The damage of the capillary network of alveolar ways together with the sclerosis of interalveolar capillaries leads to the development of pulmonary hypertension and hypertrophy of the right ventricle of heart (pulmonary heart).
More virulent bacteria and/or more severe pneumonias can be associated with destruction of lung tissue and hemorrhage. Here, alveolar walls are no longer visible because there is early abscess formation. There is also hemorrhage.
Chronic focus emphysema (emphysema pulmonum focale chronicum) occurs as a result of the expansion of acini and respiratory bronchiole round the old sites of tuberculous inflammation or post atack scars. Confluence of a few bullae results in bullous emphysema. Bullae (sub pleural blebs), which are located under the pleura, can break through the pleura cavity and cause spontaneous pneumothorax. This type of emphysema is not accompanied by pulmonary hypertension, as a capillary network is damaged in a limited area of lungs.
Compensating emphysema (emphysema pulmonum vicarum s. compensatorium) is also called vicarious emphysema. It occurs after the surgical removal of part lungs or one of lungs. This type of emphysema is accompanied by compensatory hypertrophy and hyperplasia of the remaining structures of the lungs. The cause of primary (idiopathic) emphysema is unknown. It has such typical signs a atrophy of walls of alveolar ways, reduction of capillary wall, and pulmonary
Development of senile emphysema, more precisely are emphysemas in old men, related to age-old involution of lungs.
At higher magnification, early abscessing pneumonia is shown. Alveolar walls are not clearly seen, only sheets of neutrophils.
Interstitial emphysema (emphysema pulmonum interstetiale) is characterized by the penetration of air into the interstitial tissue. The cause of such phenomenon is the destruction of alveolar ways at strong coughing motions. Through the cells of the root of the lungs, air gets into the intercellular spaces of the mediastinum (pneumomediastinum), subcutaneous cells of the neck, thorax and head (hypodermic emphysema). At pressure on the skin of the areas of increased air, a characteristic crunch (crepitation) can be heard.
This more focal abscess containing a neutrophilic exudate as well as dark blue bacterial colonies suggests aspiration or hematogenous spread of infection to the lung. Aspirated material from the oral-pharyngeal region contains bacterial flora. Hematogenous spread of infection to lungs could occur from septicemia or from infective endocarditis involving the right side of the heart.
Bronchial asthma is a chronic disease of allergic nature, which is characterized by the attacks of expiratory dyspnoea. There are two main forms of bronchial asthma– atopic and infectiously allergic. Atopic form occurs at influence of allergens of uninfectious origin on the respiratory tracts. . In the half of the cases, the disease is predefined by a dusty room in the complement of which high-allergic carbohydrates – products of disintegration of cellulose enter from a cotton plant. In addition to a dusty room the special type of allergin which causes the bronchial asthma in childhood is found. From among other allergens such, as vegetable pollens, epidermis and wool of animals, medications (acetylsalicylic acid, morphine), domestic chemicals (detergents, varnishes) are important. The infectiously allergic form of bronchial asthma develops in patients with broncho-pulmonary pathology, caused by infectious agents – viruses, bacteria and mushrooms. Pathogenesis of both forms of bronchial asthma is similar. Immunological, pathochemical and patophysiological stages are selected. In the atopic form the immunological stage is characterized by the hyperproduction and accumulation of ІgЕ. These antibodies are adsorbed in the cells of bronchiole and at the repeated introduction of antigen in respiratory tracts, interact with it by the mechanism of anaphylaxis. The reaction of immediate type is formed; the attack of dyspnoea occurs in a few minutes after the action of the antigen. At infectiously allergic bronchial asthma the immunological stage is of the mechanism of hypersensitiveness of slow type, where the leading role is played not by antibodies, but by sensibilised lymphocytes. The dyspnoea appears in 12-36 hours after a contact with the allergen.
During the pathochemical stage under the action of an antigen-antibody complex active substances- histamine acetylcholine, prostaglandin, leukotriene are released. They disturb the function of target cells in the walls of the bronchiole, – leyomiocytes, goblet and other cells. It results in bronchiospasm, hypersecretions of mucus and edema of bronchiole. Eventually ventilation functions are strongly limited affecting exhalation mainly, when due to the additional tension of respiratory muscles high intrapulmonary pressure is created. Bronchiole adhere together, and exhalation is affected or generally becomes impossible. Disorder of respiration in patients with bronchial asthma is revealed as repeated attacks of dyspnoea. During an attack there is infiltration of walls of bronchiole by eosinophiles, neutrophiles, labrocytes, and T-lymphocytes. There is an edema of mucus and submucus layers, obturation of bronchiole by mucus in which eosinophiles appear and epithelium shedding . In pulmonary tissue acute obstructive emphysema develops with the focus of atelectasis. Respiratory insufficiency which can lead to death of the patient during an attack, comes as a result. Before the chronic signs of bronchial asthma are the phenomena of diffuse chronic bronchitis, inflammation and hyalinosis of the basal membrane of bronchiole, sclerosis of intraalveolar partitions, chronic obstructive emphysema of lungs, pulmonary hypertension, hypertrophy of right ventricle of heart.
There is a localized foreign body giant cell response to the aspirated material seen here at high magnification. Aspirated material may also produce inflammation from chemical irritation, as with gastric contents.
Interstitial diseases of lungs are characterized by the primary inflammatory process in intraalveolar connective tissue (pneumonitis), also called fibrosing alveolitis. They end up with the development of diffuse pneumofibrosis.
Three nosology forms of fibrous alveolitis are distinguished:
1) idiopathic pulmonary fibrosis/chronic fibrosing alveolitis;
2) extrinsic allergic alveolitis (lung „farmer”, „poultry farmer”, „cattle-breeder”, „textile worker”, „pharmaceutist”;
3) toxic fibrous alveolitis.
Causes:
1) viral, bacterial, mycosis infection;
2) dust with the antigens of animal and vegetable origin;
3) medical preparations:, immunosuppressors, antitumor antibiotics, antidiabetic preparations and so on.
In pathogenesis the basic role is played by the immunocomplex damages of capillaries between alveolar partitions and stroma of lungs followed by cellular immune cytolysis.
Pathological anatomy is presented by three stages:
1) diffuse or granulomatous alveolitis with infiltratioeutrophiles, lymphocytes, plasmatic cells;
2) disorganization of alveolar structures and pneumofibrosis;
3) forming of cellular lungs with the development of the alveolar-capillary block, panacinar emphysema, bronchiolectasis, pulmonary hypertension, hypertrophy of the right ventricle.
The syndrome of Hamman-Rich is an acute form of fibrous alveolitis, that occurs at systemic diseases of connective tissue and active viral hepatitis.
Pneumofibrosis is a chronic process in lungs, which develops after the previous diseases of pulmonary tissue or interstitia. It is characterized by outgrowth of connective tissue, deep alteration of microcirculations, the development of pulmonary hypertension followed by hypertrophy of the right ventricle and pulmonary heart, hypoxia of pulmonary tissue, its alteration and deformation.
Almost the entire middle lobe of this right lung is involved by a chronic abscess as seen here on section. The area of abscess is yellow tan, and it was very firm.The infectious agent responsible here was Nocardia, which is known to produce chronic abscessing inflammation.
This is a microscopic appearance of chronic abscessing inflammation with large areas of pink necrotic tissue present on the left that are bordered by granulation tissue with numerous prominent capillaries filled with blood.
Here is the microscopic appearance of a viral pneumonia with interstitial lymphocytic infiltrates. Note that there is no alveolar exudate. Thus, the patient with this type of pneumonia will probably not have a productive cough. The most common causes for viral pneumonia are influenza, parainfluenza, adenovirus, and respiratory syncytial virus (RSV appears mostly in children).
Cytomegalovirus can appear in immunocompromised hosts.
This is respiratory syntytial virus (RSV) in a child. Note the giant cells which are part of the viral cytopathic effect. The inset demonstrates a typical giant cell with a round, pink intracytoplasmic inclusion. RSV accounts for many cases of pneumonia in children under 2 years, and can be a cause for death in infants 1 to 6 months of age or older.
Here is the gross appearance of a lipid pneumonia in which there is an ill-defined, pale yellow area on the left. This yellow appearance explains the term “golden” pneumonia. There are two main types of lipid pneumonia: endogenous and exogenous.
This is the microscopic appearance of an exogenous lipid pneumonia in which lipid vacuoles appear, mainly along airways, accompanied by an inflammatory response that can contain foreign body giant cells. The term exogenous refers to the origin of the lipid material outside the body. This material is aspirated into the bronchial tree.
Here is the gross appearance of a lung with tuberculosis. Scattered tan granulomas are present, mostly in the upper lung fields. Some of the larger granulomas have central caseation. Granulomatous disease of the lung grossly appears as irregularly sized rounded nodules that are firm and tan. Larger nodules may have central necrosis known as caseation–a process of necrosis that includes elements of both liquefactive and coagulative necrosis).
On closer inspection, the granulomas have areas of caseous necrosis. This is very extensive granulomatous disease. This pattern of multiple caseating granulomas primarily in the upper lobes is most characteristic of secondary (reactivation) tuberculosis. However, fungal granulomas (histoplasmosis, cryptococcosis, coccidioidomycosis) can mimic this pattern as well.
This cast of the bronchial tree is formed of inspissated mucus and was coughed up by a patient during an asthmatic attack. The outpouring of mucus from hypertrophied bronchial submucosal glands, the bronchoconstriction, and dehydration all contribute to the formation of mucus plugs that can block airways in asthmatic patients.
Between the bronchial cartilage at the right and the bronchial lumen filled with mucus at the left is a submucosa widened by smooth muscle hypertrophy, edema, and inflammation (mainly eosinophils). These are changes of bronchial asthma. The peripheral eosinophil count or the sputum eosinophils can be increased during an asthmatic attack.
A closer view demonstrates the focal area of dilated bronchi with bronchiectasis. Bronchiectasis tends to be localized with disease processes such as neoplasms and aspirated foreign bodies that block a portion of the airways. Widespread bronchiectasis is typical for patients with cystic fibrosis who have recurrent infections and obstruction of airways by mucus throughout the lungs.
This photomicrograph shows a bronchus with increased numbers of chronic inflammatory cells in the submucosa. Chronic bronchitis does not have characteristic pathologic findings, but is defined clinically as a persistent productive cough for at least three consecutive months in at least two consecutive years. Most patients are smokers. Often, there are features of emphysema as well. Since chronic bronchitis and emphysema often overlap, the term ‘chronic obstructive pulmonary disease’ (COPD) can be applied.
Professional diseases of lungs
Silicosis and anthracosis belong to the group of pneumoconiosis – professional diseases which are caused by the action of industrial dust.
The cause of silicosis is protracted inhalation of dust which contains the dioxide of silicon – SiO2. The crystalline oxide of silicon in a tissue fluid slowly dissolves and develops into colloid solution of silicic acid. The latter damages the tissue of lungs and initiates a fibrous process.
The same role in the pathogenesis of silicosis is played by the damage of the wall of lysosomes by the particles of quartz, as a result of which hydrolytic enzymes are emptied in the cytoplasm of macrophages. The products of autolysis of macrophages stimulate the proliferative activity of fibroblasts.
The course of silicosis is mostly chronic. In mucus and submucus membranes of the nose, larynx, trachea, interstitial of lungs and lymphatic nodes the phenomena of atrophy, sclerosis and formation of silicotic nodules appear. They have a round or polygonal form with grey or grey black color. In some cases silicotic nodules are built from concentric located hyaline of connective tissue cells, in other – from the wrong directed collagenase bunches. In both cases a free dust or dust appears in macrophages. They are called as dustcontaining cells– coniophagocytes.
Three forms of silicosis are distinguished. At a miliary form shallow nodes prevail by a size from millet corn. At a tumor form silicotic nodules are large, resemble a tumor and occupy the greater part of pulmonary fate or and all of fate. The diffusely sclerotic form is characterized by the negligible quantity of miliary nodes and the predominance of diffuse outgrowth of connective tissue after motion of bronchial tubes, vessels and intraalveolar partitions***
During all forms of silicosis the development of chronic bronchitis, pneumosclerosis, pulmonary hypertension, hypertrophy of right ventricle of heart are observed. Sometimes silicotic nodules can be disintegration with the formation of silicate cavity. In the formation of cavities of importance is the instability of newly formed connective tissue. In particular, it is less steady to collagenosis. Tuberculosis often accompanies silicosis. In such cases the disease is called silicotuberculosis.
Anthracosis occurs at the protracted inhalation of coal dust. The disease is characterized by the development of connective tissue in the areas of the deposition of the coal dust – in intraalveolar partitions, bronchial tubes and vessels. Connective tissue overgrows round the accumulations of dust, not shown out coniophagocytes through a bronchial tree or lymphatic vessels. Such nodes are called anthracotic.
At the infiltration of lymphatic nodes by coal dust and their sclerosis there is the stagnation of lymph, hypoxia and acidosis of the stroma of lungs. This leads to black induration of lungs is developed.
Anthracosis is accompanied by chronic bronchitis, emphysema, pulmonary hypertension and bronchopneumonia. As a result of the disorders of blood circulation and direct influencing of coal dust sometimes there is necrosis and softening of pulmonary tissue with the formation of cavities. This form of anthracosis is accompanied by haemoptysis and, resembles secondary tuberculosis, through called black consumption.
The cancer of lungs occupies the first position among malignant tumors in men and the second – in women. The death rate for it is 26 %.
The cancer of bronchial tubes occurs mainly in smokers (90%). Of important role are the carcinogenic substances which penetrate blood and lymph.
To the precancer states belong chronic bronchitis, bronchiectasis,, and to the precancer changes – hyperplasia, displasia and metaplasia of the epithelium.
As a rule, the cancer of lungs develops from the epithelium of bronchial tubes (bronchogenic, central cancer), rarely – from the epithelium of bronchiole and alveolar epithelium (pneumogenic, peripheral cancer). Pathogenesis of central cancer is related to such precancer changes, as basal-cellular hyperplasia, dysplasia and squamous cellular metaplasia of the epithelium of bronchial tubes. For the morphogenesis of peripheral cancer, the main characteristic is a wider spectrum of pre-tumor changes. Foremost, they are related to the development of pneumosclerosis after inflammation, to heart attack and so on. Substances which are instrumental in malignant transformation are created in the scar, namely the deposition of carcinogens, local immunosuppression, disorder of intercellular connections.
According to А.І.Strukov classification of cancer of lungs foresees a division after localization, character of growth, macroscopic form and microscopic kind.
According to localization the following forms are selected:
1) periapical (central) cancer which developes from an epithelium a barrel lobular and initial part of bronchial tube, grows as a node or polypus of white color and dense consistency;
2) peripheral cancer which developes from the peripheral part of bronchial tube and its branches, and also from alveolar epithelium, exophiticaly grows for a long time and often developes in the area of scar;
3) the mixed (massive) cancer reveals itself as soft tissue of white color, which can occupy part or all of lung.
According to character of growth endophitic (endobronchial) and exophitic (exobronchial and peribronchial) cancers are distinguished.
According to macroscopic form a cancer is plague-like, polypus, endobronchial diffuse, ramified and nodal ramified cancer.
According to microscopic structure squarmous cellular (epidermoid) cancer, undifferentiated, anaplastic caner (finecellular, largecellular, oastmealcellular), golden-flatcellular cancer, of bronchial glands – adenoidno-cystous and mucoepidermoid are distinguished.
Metastasis outside an organ is a characteristic of a central cancer. At endophitic growth it spreads to the tissue of mediastinum, pericardium and pleura. Peripheral and mixed cancers spread within the limits of the organ, germinating tissue of the bronchial tubes and pleura. The cancer of lungs metastases by lymphogenic and hematogenic ways. Lymphogenic metastases occur in the peribronchial, bifurcational, neck and other lymphatic nodes, hematogenic – to the cerebrum, bones (mainly vertebrae), and adrenal glands. For central cancer, lymphogenic metastases are typical, for peripheral – hematogenic. First clinical sign of peripheral cancer, which developes in the area of scar and has a small sizes (microcarcinoma), related to the plural hematogenic metastases.
Permanent complication of cancer of lungs, especially central, is the development of atelectasis. Pneumonias, abscesses, bronchiectasis, bleeding which mask the course of cancer, develops as a result of the disorder of the drainage function. The distribution on the pleura causes the development of serous-hemorrhagic and hemorrhagic pleuritis, and also to carcinom of the pleura. Cachexia during the cancer of lungs develops later than during the cancer of the stomach.
The pleuritis is the inflammation of pleura which frequently occurs as the complication of some of visceral pathologies. Often occurs at diseases of the lungs: pneumonias, ischemic heart disease, cancer, tuberculosis etc., at rheumatism and other system diseases of connective tissue (allergic pleuritis), and also diseases of kidneys (pleuritis of uremia). According to the character of inflammations pleuritis serous, fibrinous, sero-fibrinous, purulent, hemorrhagic types are distinguished.
