(BQ) Part 2 book Textbook of pathology presentation of content: The blood vessels and lymphatics, the heart, the respiratory system, the oral cavity and salivary glands, the gastrointestinal tract, the kidney and lower urinary tract, the male reproductive system and prostate, the female genital tract, the endocrine system, the musculoskeletal system,...and other contents.
390 Section III SYSTEMIC PATHOLOGY The Blood Vessels and Lymphatics Chapter 15 The blood vessels are closed circuits for the transport of blood from the left heart to the metabolising cells, and then back to the right heart The blood containing oxygen, nutrients and metabolites is routed through arteries, arterioles, capillaries, venules and veins These blood vessels differ from each other in their structure and function SECTION III ARTERIES NORMAL STRUCTURE Depending upon the calibre and certain histologic features, arteries are divided into types: large (elastic) arteries, medium-sized (muscular) arteries and the smallest arterioles Systemic Pathology Histologically, all the arteries of the body have layers in their walls: the tunica intima, the tunica media and the tunica adventitia These layers progressively decrease with diminution in the size of the vessels Tunica intima This is the inner coat of the artery It is composed of the lining endothelium, subendothelial connective tissue and bounded externally by internal elastic lamina Endothelium is a layer of flattened cells adjacent to the flowing blood Narrow junctions exist between the adjoining endothelial cells through which certain materials pass The integrity of the endothelial layer is of paramount importance in maintenance of vascular functions since damage to it is the most important event in the initiation of thrombus formation at the site Subendothelial tissue consists of loose meshwork of connective tissue that includes myointimal cells, collagen, proteoglycans, elastin and matrix glycoproteins Internal elastic lamina is a layer of elastic fibres having minute fenestrations Tunica media Tunica media is the middle coat of the arterial wall, bounded internally by internal elastic lamina and externally by external elastic lamina This layer is the thickest and consists mainly of smooth muscle cells and elastic fibres The external elastic lamina consisting of condensed elastic tissue is less well defined than the internal elastic lamina Tunica adventitia The outer coat of arteries is the tunica adventitia It consists of loose mesh of connective tissue and some elastic fibres that merge with the adjacent tissues This layer is rich in lymphatics and autonomic nerve fibres The layers of arterial wall receive nutrition and oxygen from sources: Tunica intima and inner third of the media are nourished by direct diffusion from the blood present in the lumen Outer two-thirds of the media and the adventitia are supplied by vasa vasora (i.e vessels of vessels), the nutrient vessels arising from the parent artery As the calibre of the artery decreases, the three layers progressively diminish Thus, there are structural variations in the three types of arteries: Large, elastic arteries such as the aorta, innominate, common carotid, major pulmonary, and common iliac arteries have very high content of elastic tissue in the media and thick elastic laminae and hence the name Medium-sized, muscular arteries are the branches of elastic arteries All the three layers of arterial wall are thinner than in the elastic arteries The internal elastic lamina appears as a single wavy line while the external elastic lamina is less prominent The media primarily consists of smooth muscle cells and some elastic fibres (Fig 15.1) Arterioles are the smallest branches with internal diameter 20-100 μm Structurally, they consist of the three layers as in muscular arteries but are much thinner and cannot be distinguished The arterioles consist of a layer of endothelial cells in the intima, one or two smooth muscle cells in the media and small amount of collagen and elastic tissue comprising the adventitia The elastic laminae are virtually lost Capillaries are about the size of an RBC (7-8 μm) and have a layer of endothelium but no media Blood from capillaries returns to the heart via post-capillary venules and thence into venules and then veins In the following pages, diseases of arteries are discussed under major headings: arteriosclerosis, arteritis (vasculitis) and aneurysms This is followed by brief account of diseases of veins and lymphatics, while the vascular tumours are described at the end of the chapter hyperplastic arteriolosclerosis and necrotising arteriolitis All 391 the three types are common in hypertension but may occur due to other causes as well Hyaline Arteriolosclerosis Hyaline sclerosis is a common arteriolar lesion that may be seen physiologically due to aging, or may occur pathologically in benign nephrosclerosis in hypertensives and as a part of microangiopathy in diabetics; the subject is discussed again in Chapter 22 MORPHOLOGIC CHANGES The visceral arterioles are particularly involved The vascular walls are thickened and the lumina narrowed or even obliterated Figure 15.1 The structure of a medium-sized muscular artery ARTERIOSCLEROSIS Senile arteriosclerosis is the thickening of media and intima of the arteries seen due to aging The changes are nonselective and affect most of the arteries These are possibly induced by stress and strain on vessel wall during life MORPHOLOGIC FEATURES The changes are as under: Fibroelastosis: The intima and media are thickened due to increase in elastic and collagen tissue Elastic reduplication: The internal elastic lamina is split or reduplicated so that two wavy layers are seen Eventually, the fibrotic changes result in age-related elevation of systolic blood pressure HYPERTENSIVE ARTERIOLOSCLEROSIS Hypertension is the term used to describe an elevation in blood pressure Pathology of forms of hypertension— systemic, pulmonary and portal, is discussed in detail with diseases of the kidneys (Chapter 22), lungs (Chapter 17) and liver (Chapter 21) respectively Arteriolosclerosis is the term used to describe morphologic forms of vascular disease affecting arterioles and small muscular arteries These are: hyaline arteriolosclerosis, Hyperplastic Arteriolosclerosis The hyperplastic or proliferative type of arteriolosclerosis is a characteristic lesion of malignant hypertension; other causes include haemolytic-uraemic syndrome, scleroderma and toxaemia of pregnancy MORPHOLOGIC FEATURES The morphologic changes affect mainly the intima, especially of the interlobular arteries in the kidneys Three types of intimal thickening may occur i) Onion-skin lesion consists of loosely-placed concentric layers of hyperplastic intimal smooth muscle cells like the bulb of an onion The basement membrane is also thickened and reduplicated (Fig 15.2, B) ii) Mucinous intimal thickening is the deposition of amorphous ground substance, probably proteoglycans, with scanty cells iii) Fibrous intimal thickening is less common and consists of bundles of collagen, elastic fibres and hyaline deposits in the intima Severe intimal sclerosis results in narrowed or obliterated lumen With time, the lesions become more and more fibrotic The Blood Vessels and Lymphatics SENILE ARTERIOSCLEROSIS PATHOGENESIS The exact pathogenesis is not known However, the following hypotheses have been proposed: i) The lesions result most probably from leakage of components of plasma across the vascular endothelium This is substantiated by the demonstration of immunoglobulins, complement, fibrin and lipids in the lesions The permeability of the vessel wall is increased, due to haemodyanamic stress in hypertension and metabolic stress in diabetes, so that these plasma components leak out and get deposited in the vessel wall ii) An alternate possibility is that the lesions may be due to immunologic reaction iii) Some have considered it to be normal aging process that is exaggerated in hypertension and diabetes mellitus CHAPTER 15 Arteriosclerosis is a general term used to include all conditions with thickening and hardening of the arterial walls The following morphologic entities are included under arteriosclerosis: I Senile arteriosclerosis II Hypertensive arteriolosclerosis III Mönckeberg’s arteriosclerosis (Medial calcific sclerosis) IV Atherosclerosis The last-named, atherosclerosis, is the most common and most important form of arteriosclerosis; if not specified, the two terms are used interchangeably with each other Microscopically, the thickened vessel wall shows structureless, eosinophilic, hyaline material in the intima and media (Fig 15.2,A) 392 Figure 15.2 Diagrammatic representation of three forms of arteriolosclerosis, commonly seen in hypertension SECTION III PATHOGENESIS The pathogenesis of hyperplastic intimal thickening is unclear Probably, the changes result following endothelial injury from systemic hypertension, hypoxia or immunologic damage leading to increased permeability A healing reaction occurs in the form of proliferation of smooth muscle cells with fibrosis Necrotising Arteriolitis Systemic Pathology In cases of severe hypertension and malignant hypertension, parts of small arteries and arterioles show changes of hyaline sclerosis and parts of these show necrosis, or necrosis may be superimposed on hyaline sclerosis However, hyaline sclerosis may not be always present in the vessel wall MORPHOLOGIC FEATURES Besides the changes of hyaline sclerosis, the changes of necrotising arteriolitis include fibrinoid necrosis of vessel wall, acute inflammatory infiltrate of neutrophils in the adventitia Oedema and haemorrhages often surround the affected vessels (Fig 15.2,C) MORPHOLOGIC FEATURES Medial calcification is often an incidental finding in X-rays of the affected sites having muscular arteries The deposition of calcium salts in the media produces pipestem-like rigid tubes without causing narrowing of the lumen Microscopically, Mönckeberg’s arteriosclerosis is characterised by deposits of calcium salts in the media without associated inflammatory reaction while the intima and the adventitia are spared (Fig 15.3) Often, coexistent changes of atherosclerosis are present altering the histologic appearance PATHOGENESIS Pathogenesis of this condition is not known but it is considered as an age-related physiologic change due to prolonged effect of vasoconstriction PATHOGENESIS Since necrotising arteriolitis occurs in vessels in which there is sudden and great elevation of pressure, the changes are said to result from direct physical injury to the vessel wall MÖNCKEBERG’S ARTERIOSCLEROSIS (MEDIAL CALCIFIC SCLEROSIS) Mönckeberg’s arteriosclerosis is calcification of the media of large and medium-sized muscular arteries, especially of the extremities and of the genital tract, in persons past the age of 50 The condition occurs as an age-related degenerative process, and therefore, an example of dystrophic calcification, and has little or no clinical significance However, medial calcification also occurs in some pathological states like pseudoxanthoma elasticum and in idiopathic arterial calcification of infancy Figure 15.3 Monckeberg’s arteriosclerosis (medial calcific sclerosis) There is calcification exclusively in the tunica media unassociated with any significant inflammation ATHEROSCLEROSIS Definition Atherosclerosis is a specific form of arteriosclerosis affecting primarily the intima of large and medium-sized muscular arteries and is characterised by fibrofatty plaques or atheromas The term atherosclerosis is derived from athero(meaning porridge) referring to the soft lipid-rich material in the centre of atheroma, and sclerosis (scarring) referring to connective tissue in the plaques Atherosclerosis is the commonest and the most important of the arterial diseases Though any large and medium-sized artery may be involved in atherosclerosis, the most commonly affected are the aorta, the coronary and the cerebral arterial systems Therefore, the major clinical syndromes resulting from ischaemia due to atherosclerosis pertain to the heart (angina and myocardial infarcts or heart attacks), and the brain (transient cerebral ischaemia and cerebral infarcts or strokes); other sequelae are peripheral vascular disease, aneurysmal dilatation due to weakened arterial wall, chronic ischaemic heart disease, ischaemic encephalopathy and mesenteric arterial occlusion TABLE 15.1: Risk Factors in Atherosclerosis I MAJOR RISK FACTORS II EMERGING RISK FACTORS A) Modifiable Environmental influences Dyslipidaemia Obesity Hypertension Hormones:oestrogen defi3 Diabetes mellitus ciency, oral contraceptives Smoking Physical inactivity B) Constitutional Stressful life Age Homocystinuria Sex Role of alcohol Genetic factors Prothrombotic factors Familial and racial factors Infections (C.pneumoniae, Herpesvirus, CMV) 10 High CRP MAJOR RISK FACTORS MODIFIABLE BY LIFE STYLE AND/OR THERAPY There are four major risk factors in atherogenesis—lipid disorders, hypertension, cigarette smoking and diabetes mellitus DYSLIPIDAEMIAS Virchow in 19th century first identified cholesterol crystals in the atherosclerotic lesions Since then, extensive information on lipoproteins and their role in atherosclerotic lesions has been gathered Abnormalities in plasma lipoproteins have been firmly established as the most important major risk factor for atherosclerosis It has been firmly established that hypercholesterolaemia has directly proportionate relationship with atherosclerosis and IHD The following evidences are cited in support of this: i) The atherosclerotic plaques contain cholesterol and cholesterol esters, largely derived from the lipoproteins in the blood ii) The lesions of atherosclerosis can be induced in experimental animals by feeding them with diet rich in cholesterol iii) Individuals with hypercholesterolaemia due to various causes such as in diabetes mellitus, myxoedema, nephrotic syndrome, von Gierke’s disease, xanthomatosis and familial hypercholesterolaemia have increased risk of developing atherosclerosis and IHD iv) Populations having hypercholesterolaemia have higher mortality from IHD Dietary regulation and administration of cholesterol-lowering drugs have beneficial effect on reducing the risk of IHD The concentration of total cholesterol in the serum reflects the concentrations of different lipoproteins in the serum The lipoproteins are divided into classes according to the density of solvent in which they remain suspended on centrifugation at high speed The major classes of lipoprotein particles are chylomicrons, very-low density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL) Lipids are insoluble in blood and therefore are carried in circulation and across the cell membrane by carrier proteins called apoproteins Apoprotein surrounds the lipid for carrying it, The Blood Vessels and Lymphatics Atherosclerosis is widely prevalent in industrialised countries However, majority of the data on etiology are based on the animal experimental work and epidemiological studies The incidences for atherosclerosis quoted in the literature are based on the major clinical syndromes produced by it, the most important interpretation being that death from myocardial infarction is related to underlying atherosclerosis Cardiovascular disease, mostly related to atherosclerotic coronary heart disease or ischaemic heart disease (IHD) is the most common cause of premature death in the developed countries of the world It is estimated that by the year 2020, cardiovascular disease, mainly atherosclerosis, will become the leading cause of total global disease burden Systematic large scale studies of investigations on living populations have revealed a number of risk factors which are associated with increased risk of developing clinical atherosclerosis Often, they are acting in combination rather than singly These risk factors are divided into two groups (Table 15.1): II Non-traditional emerging risk factors This includes a host of factors whose role in atherosclerosis is minimal, and in some cases, even uncertain Apparently, a combination of etiologic risk factors have additive effect in producing the lesions of atherosclerosis CHAPTER 15 Etiology I Major risk factors These are further considered under 393 headings: A) Major risk factors modifiable by life style and/or therapy: This includes major risk factors which can be controlled by modifying life style and/or by pharmacotherapy and includes: dyslipidaemias, hypertension, diabetes mellitus and smoking B) Constitutional risk factors: These are non-modifiable major risk factors that include: increasing age, male sex, genetic abnormalities, and familial and racial predisposition 394 TABLE 15.2: Fractions of Lipoproteins in Serum Classes Sites of Synthesis Normal Serum Levels Role in Atherosclerosis HDL cholesterol Liver, intestine > 60 mg/dl Protective LDL cholesterol Liver < 130 mg/dl Maximum VLDL triglycerides Intestine, liver < 160 mg/dl Less marked Chylomicrons Liver, intestine, macrophage SECTION III Systemic Pathology different apoproteins being named by letter A, B, C, D etc while their subfractions are numbered serially The major fractions of lipoproteins tested in blood lipid profile and their varying effects on atherosclerosis and IHD are as under (Table 15.2): i) Total cholesterol: Desirable normal serum level is 140-200 mg/dl, while levels of borderline high are considered between 200-240 mg/dl An elevation of total serum cholesterol levels above 260 mg/dl in men and women between 30 and 50 years of age has three times higher risk of developing IHD as compared with people with total serum cholesterol levels within normal limits ii) Triglycerides: Normal serum level is below 160 mg/dl iii) Low-density lipoproteins (LDL) cholesterol: Normal optimal serum level is 55 years) The prevalence of atherosclerotic IHD is about three times higher in men in 4th decade than in women and the difference slowly declines with age but remains higher at all ages in men The lower incidence of IHD in women, especially in premenopausal age, is probably due to high levels of oestrogen and high-density lipoproteins, both of which have anti-atherogenic influence GENETIC FACTORS Genetic factors play a significant role in atherogenesis Hereditary genetic derangements of lipoprotein metabolism predispose the individual to high blood lipid level and familial hypercholesterolaemia EMERGING RISK FACTORS As stated above, atherosclerosis is not caused by a single etiologic factor but is a multifactorial process whose exact pathogenesis is still not known Since the times of Virchow, a number of theories have been proposed Insudation hypothesis The concept hypothesised by Virchow in 1856 that atherosclerosis is a form of cellular proliferation of the intimal cells resulting from increased imbibing of lipids from the blood came to be called the ‘lipid theory’ Modified form of this theory is currently known as ‘response to injury hypothesis’ and is now-a-days the most widely accepted theory Encrustation hypothesis The proposal put forth by Rokitansky in 1852 that atheroma represented a form of encrustation on the arterial wall from the components in the blood forming thrombi composed of platelets, fibrin and leucocytes, was named as ‘encrustation theory’ or ‘thrombogenic theory’ Since currently it is believed that encrustation or thrombosis is not the sole factor in atherogenesis but the components of thrombus (platelets, fibrin and leucocytes) have a role in atheromatous lesions, this theory has now been incorporated into the response-to-injury hypothesis mentioned above Though, there is no consensus regarding the origin and progression of lesion of atherosclerosis, the role of four key factors—arterial smooth muscle cells, endothelial cells, blood monocytes and dyslipidaemia, is accepted by all However, the areas of disagreement exist in the mechanism and sequence of events involving these factors in initiation, progression and complications of disease Currently, pathogenesis of atherosclerosis is explained on the basis of the following two theories: Reaction-to-injury hypothesis, first described in 1973, and modified in 1986 and 1993 by Ross Monoclonal theory, based on neoplastic proliferation of smooth muscle cells, postulated by Benditt and Benditt in 1973 REACTION-TO-INJURY HYPOTHESIS This theory is most widely accepted and incorporates aspects of two older historical theories of atherosclerosis—the lipid theory of Virchow and thrombogenic (encrustation) theory of Rokitansky The original response to injury theory was first described in 1973 according to which the initial event in atherogenesis was considered to be endothelial injury followed by smooth muscle cell proliferation so that the early lesions, according to this theory, consist of smooth muscle cells mainly The modified response-to-injury hypothesis described subsequently in 1993 implicates lipoprotein entry into the intima as the initial event followed by lipid accumulation in the macrophages (foam cells now) which according to modified theory, are believed to be the dominant cells in early lesions The Blood Vessels and Lymphatics There are a number of nontraditional newly emerging risk factors for which the role in the etiology of atherosclerosis is yet not fully supported These factors are as under: Higher incidence of atherosclerosis in developed countries and low prevalence in underdeveloped countries, suggesting the role of environmental influences Obesity, if the person is overweight by 20% or more, is associated with increased risk Use of exogenous hormones (e.g oral contraceptives) by women or endogenous oestrogen deficiency (e.g in postmenopausal women) has been shown to have an increased risk of developing myocardial infarction or stroke Physical inactivity and lack of exercise are associated with the risk of developing atherosclerosis and its complications Stressful life style, termed as ‘type A’ behaviour pattern, characterised by aggressiveness, competitive drive, ambitiousness and a sense of urgency, is associated with enhanced risk of IHD compared with ‘type B’ behaviour of relaxed and happy-go-lucky type Patients with homocystinuria, an uncommon inborn error of metabolism, have been reported to have early atherosclerosis and coronay artery disease There are some reports which suggest that moderate consumption of alcohol has slightly beneficial effect by raising the level of HDL cholesterol Prothrombotic factors and elevated fibrinogen levels favour formation of thrombi which is the gravest complication of atherosclerosis Role of infections, particularly of Chlamydia pneumoniae and viruses such as herpesvirus and cytomegalovirus, has been found in coronary atherosclerotic lesions by causing inflammation Possibly, infections may be acting in combination with some other factors Pathogenesis CHAPTER 15 FAMILIAL AND RACIAL FACTORS: The familial predisposition to atherosclerosis may be related to other risk factors like diabetes, hypertension and hyperlipoproteinaemia Racial differences too exist; Blacks have generally less severe atherosclerosis than Whites 10 Markers of inflammation such as elevated C reactive protein, 395 an acute phase reactant, correlate with risk of developing atherosclerosis In man, two of the major risk factors which act together to produce endothelial injury are: haemodynamic stress from hypertension and chronic dyslipidaemia The role of haemodynamic forces in causing endothelial injury is further supported by the distribution of atheromatous plaques at points of bifurcation or branching of blood vessels which are under greatest shear stress 396 ii) Intimal smooth muscle cell proliferation Endothelial injury causes adherence, aggregation and platelet release reaction at the site of exposed subendothelial connective tissue and infiltration by inflammatory cells Proliferation of intimal smooth muscle cell and production of extracellular matrix are stimulated by various cytokines such as IL-1 and TNF-α released from invading monocyte-macrophages and by activated platelets at the site of endothelial injury These cytokines lead to local synthesis of following growth factors having distinct roles in plaque evolution: Platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) stimulate proliferation and migration of smooth muscle cells from their usual location in the media into the intima SECTION III Transforming growth factor-β (TGF-β) and interferon(IFN-γ) derived from activated T lymphocytes within lesions regulate the synthesis of collagen by smooth muscle cells Smooth muscle cell proliferation is also facilitated by biomolecules such as nitric oxide and endothelin released from endothelial cells Intimal proliferation of smooth muscle cells is accompanied by synthesis of matrix proteins—collagen, elastic fibre proteins and proteoglycans Systemic Pathology iii) Role of blood monocytes Though blood monocytes not possess receptors for normal LDL, LDL does appear in the monocyte cytoplasm to form foam cell by mechanism illustrated in Fig 15.5 Plasma LDL on entry into the intima undergoes oxidation The ‘oxidised LDL’ formed in the intima performs the following all-important functions on monocytes and endothelium: Figure 15.4 Diagrammatic representation of pathogenesis of atherosclerosis as explained by ‘reaction-to-injury’ hypothesis A, Endothelial injury B, Adhesion of platelets and migration of blood monocytes from blood stream C, Smooth muscle cell proliferation into the intima and ingrowth of new blood vessels Both these theories—original and modified, have attracted support and criticism However, following is the generally accepted role of key components involved in atherogenesis, diagrammatically illustrated in Fig 15.4 i) Endothelial injury It has been known for many years that endothelial injury is the initial triggering event in the development of lesions of atherosclerosis Actual endothelial denudation is not an essential requirement, but endothelial dysfunction may initiate the sequence of events Numerous causes ascribed to endothelial injury in experimental animals are: mechanical trauma, haemodynamic forces, immunological and chemical mechanisms, metabolic agent as chronic dyslipidaemia, homocystine, circulating toxins from systemic infections, viruses, hypoxia, radiation, carbon monoxide and tobacco products For monocytes: Oxidised LDL acts to attract, proliferate, immobilise and activate them as well as is readily taken up by scavenger receptor on the monocyte to transform it to a lipid-laden foam cell For endothelium: Oxidised LDL is cytotoxic Death of foam cell by apoptosis releases lipid to form lipid core of plaque iv) Role of dyslipidaemia As stated already, chronic dyslipidaemia in itself may initiate endothelial injury and dysfunction by causing increased permeability In particular, hypercholesterolaemia with increased serum concentration of LDL promotes formation of foam cells, while high serum concentration of HDL has anti-atherogenic effect v) Thrombosis As apparent from the foregoing, endothelial injury exposes subendothelial connective tissue resulting in formation of small platelet aggregates at the site and causing proliferation of smooth muscle cells This causes mild inflammatory reaction which together with foam cells is incorporated into the atheromatous plaque The lesions enlarge by attaching fibrin and cells from the blood so that thrombus becomes a part of atheromatous plaque 397 CHAPTER 15 Figure 15.5 Mechanism of foam cell formation The Blood Vessels and Lymphatics MONOCLONAL HYPOTHESIS This hypothesis is based on the postulate that proliferation of smooth muscle cells is the primary event and that this proliferation is monoclonal in origin similar to cellular proliferation in neoplasms (e.g in uterine leiomyoma, Chapter 8) The evidence cited in support of monoclonal hypothesis is the observation on proliferated smooth muscle cells in atheromatous plaques which have only one of the two forms of glucose-6-phosphate dehydrogenase (G6PD) isoenzymes, suggesting monoclonality in origin The monoclonal proliferation of smooth muscle cells in atherosclerosis may be initiated by mutation caused by exogenous chemicals (e.g cigarette smoke), endogenous metabolites (e.g lipoproteins) and some viruses (e.g Marek’s disease virus in chickens, herpesvirus) MORPHOLOGIC FEATURES Early lesions in the form of diffuse intimal thickening, fatty streaks and gelatinous lesions are often the forerunners in the evolution of atherosclerotic lesions However, the clinical disease states due to luminal narrowing in atherosclerosis are caused by fully developed atheromatous plaques and complicated plaques (Fig 15.6) FATTY STREAKS AND DOTS Fatty streaks and dots on the intima by themselves are harmless but may be the precursor lesions of atheromatous plaques They are seen in all races of the world and begin to appear in Figure 15.6 Schematic evolution of lesions in atherosclerosis the first year of life However, they are uncommon in older persons and are probably absorbed They are especially prominent in the aorta and other major arteries, more often on the posterior wall than the anterior wall 398 SECTION III Figure 15.7 Structure of a fully-developed atheroma The opened up inner surface of the abdominal aorta shows a variety of atheromatous lesions While some are raised yellowish-white lesions raised above the surface, a few have ulcerated surface Orifices of some of the branches coming out of the wall are narrowed by the atherosclerotic process Systemic Pathology Grossly, the lesions may appear as flat or slightly elevated and yellow They may be either in the form of small, multiple dots, about mm in size, or in the form of elongated, beaded streaks Microscopically, fatty streaks lying under the endothelium are composed of closely-packed foam cells, lipidcontaining elongated smooth muscle cells and a few lymphoid cells Small amount of extracellular lipid, collagen and proteoglycans are also present GELATINOUS LESIONS Gelatinous lesions develop in the intima of the aorta and other major arteries in the first few months of life Like fatty streaks, they may also be precursors of plaques They are round or oval, circumscribed grey elevations, about cm in diameter Microscopically, gelatinous lesions are foci of increased ground substance in the intima with thinned overlying endothelium ATHEROMATOUS PLAQUES A fully developed atherosclerotic lesion is called atheromatous plaque, also called fibrous plaque, fibrofatty plaque or atheroma Unlike fatty streaks, atheromatous plaques are selective in different geographic locations and races and are seen in advanced age These lesions may develop from progression of early lesions of the atherosclerosis described above Most often and most severely affected is the abdominal aorta, though smaller lesions may be seen in descending thoracic aorta and aortic arch The major branches of the aorta around the ostia are often severely involved, especially the iliac, femoral, carotid, coronary, and cerebral arteries Grossly, atheromatous plaques are white to yellowishwhite lesions, varying in diameter from 1-2 cm and raised on the surface by a few millimetres to a centimetre in thickness (Fig 15.7) Cut section of the plaque reveals the luminal surface as a firm, white fibrous cap and a central core composed of yellow to yellow-white, soft, porridgelike material and hence the name atheroma Microscopically, the appearance of plaque varies depending upon the age of the lesion However, the following features are invariably present (Fig 15.8): Superficial luminal part of the fibrous cap is covered by endothelium, and is composed of smooth muscle cells, dense connective tissue and extracellular matrix containing proteoglycans and collagen Cellular area under the fibrous cap is comprised by a mixture of macrophages, foam cells, lymphocytes and a few smooth muscle cells which may contain lipid Deeper central soft core consists of extracellular lipid material, cholesterol clefts, fibrin, necrotic debris and lipidladen foam cells In older and more advanced lesions, the collagen in the fibrous cap may be dense and hyalinised, smooth muscle cells may be atrophic and foam cells are fewer COMPLICATED PLAQUES Various pathologic changes that occur in fully-developed atheromatous plaques are called the complicated lesions These account for the most serious harmful effects of atherosclerosis and even death These changes include calcification, ulceration, thrombosis, haemorrhage and aneurysmal dilatation It is not uncommon to see more than one form of complication in a plaque 399 Figure 15.8 Histologic appearance of a fully-developed atheroma iii) Thrombosis The ulcerated plaque and the areas of endothelial damage are vulnerable sites for formation of superimposed thrombi These thrombi may get dislodged to become emboli and lodge elsewhere in the circulation, or may get organised and incorporated into the arterial wall as mural thrombi Mural thrombi may become occlusive thrombi which may subsequently recanalise iv) Haemorrhage Intimal haemorrhage may occur in an atheromatous plaque either from the blood in the vascular lumen through an ulcerated plaque, or from rupture of thin-walled capillaries that vascularise the atheroma from adventitial vasa vasorum Haemorrhage is particularly a common complication in coronary arteries The haematoma formed at the site contains numerous haemosiderin-laden macrophages v) Aneurysm formation Though atherosclerosis is primarily an intimal disease, advanced lesions are associated with secondary changes in the media and adventitia The changes in media include atrophy and thinning of the media and fragmentation of internal elastic lamina The adventitia undergoes fibrosis and some inflammatory changes These changes cause weakening in the arterial wall resulting in aneurysmal dilatation Clinical Effects Figure 15.9 Complicated atheromatous plaque lesion There is narrowing of the lumen of coronary due to fully developed atheromatous plaque which has dystrophic calcification in its core The clinical effects of atherosclerosis depend upon the size and type of arteries affected In general, the clinical effects result from the following: Slow luminal narrowing causing ischaemia and atrophy Sudden luminal occlusion causing infarction necrosis The Blood Vessels and Lymphatics ii) Ulceration The layers covering the soft pultaceous material of an atheroma may ulcerate as a result of haemodynamic forces or mechanical trauma This results in discharge of emboli composed of lipid material and debris into the blood stream, leaving a shallow, ragged ulcer with yellow lipid debris in the base of the ulcer Occasionally, atheromatous plaque in a coronary artery may suddenly rupture into the arterial lumen forcibly and cause thromboembolic occlusion CHAPTER 15 i) Calcification Calcification occurs more commonly in advanced atheromatous plaques, especially in the aorta and coronaries The diseased intima cracks like an eggshell when the vessel is incised and opened Microscopically, the calcium salts are deposited in the vicinity of necrotic area and in the soft lipid pool deep in the thickened intima (Fig 15.9) This form of atherosclerotic intimal calcification differs from Mönckeberg’s medial calcific arteriosclerosis that affects only the tunica media (page 392) 918 Dupuytren’s contracture, 170 Dura mater, 872 Durozier sign, 451 Dust diseases, lung, 487-93 Dwarfism, achondroplasia, 833 hypothyroid, 803 pituitary, 795 Dysenteries, 572-73 amoebic, 572-73 bacillary, 572 Dysfunctional uterine bleeding (DUB), 731-32 Dysgenetic gonads, 707 Dysgerminoma ovary, 747 Dyskeratosis, 769 Dyslipidaemia, 393-94, 661 Dysplasia, bronchopulmonary, 465 cervical, 271-72, 725-28 developmental, 256 fibromuscular, arteries, 409 fibrous, 837-38 mammary, 756-57 oral cavity, 525-26 renal cystic, 657 skeletal, 834 Dystraphic anomalies, 256, 873 Dystrophic calcification, 52 Dystrophy, muscular, 858-59 Dystrophy, vulval, 721, 722f D-xylose test, 574 E INDEX Ear, 513-15 cauliflower, 514 normal structure of, 513-14 tumours and tumour-like lesions of, 514-15 Ecchymoses, 107, 331 Eccrine hidradenoma, 786 Eccrine, poroma, 786 spiradenoma, 786 Eccrine tumours, 786 Echinococcosis, 187t, 616-17 Ectopia, 256 Ectopia vesicae (exstrophy), 698 Ectopic hormone production, 232, 502, 696 Ectopic tubal pregnancy, 739 Eczema, 770 Effusions, pleural, 505 cytology of, 273-74 Ehler-Danlos syndrome, 331 Ehrlich, Paul, 4f Elastic fibres, 170 Elastofibroma, 862 Electrical injury, 28, 242 Electrolytes, disturbances of, 93-94, 103 Electron microscope, 14-15 Electrophoresis, haemoglobin, 324, 383 Electrophoresis in myeloma, 383 Elephantiasis, 97, 411, 706 Elliptocytosis, hereditary, 293f, 315 Embden-Meyerhof pathway, 289, 317f Embolism, 119-24 air, 122-23 amniotic fluid, 123-24 arterial, 120f atheromatous, 124 classification of, 120t fat, 121-22 gas, 12-23 miscellaneous, 124 paradoxical, 119 pulmonary, 120-21 retrograde, 120 saddle, 120 systemic, 121 thromboembolism, 120-21 tumour, 124 venous, 120t Embolus, 119 Embryoma, 193, 637 Embryonal carcinoma testis, 710-11 Embryonal tumours, 206-07 Emigration, 134 Emphysema, 478-83 bullous, 480f centriacinar, 481 centrilobular, 481 classification of, 478t clinical features of, 480-81 etiopathogenesis of, 479-80 interstitial, 483 irregular, 482 morphologic features of, 480-82 morphology of individual types of, 481-82 overinflation, 482-83 panacinar, 481-82 paraseptal, 482 senile, 482 surgical, 483 versus predominant bronchitis, 479 Empty-sella syndrome, 794-95 Empyema, appendix, 579 gallbladder, 642 nasal sinus, 515 thoracis, 504 Enamel, 528 Encephalitis, 877-79 bacterial, 877 fungal, 879 HIV, 878 protozoal, 879 viral, 877-78 Encephalocele, 873 Encephalomalacia, 126 Encephalomyelitis, acute disseminated, 884 perivenous, 884 Encephalopathy, hepatic, 632 Encephalopathy, ischaemic-hypoxic, 879-80 Encephalopathy, spongiform, 878 Enchondroma, 844-45 Encrustation theory, 395 End-stage kidney, 674-75 Endarteritis obliterans, 400-01 Endocardial fibroelastosis, 455 Endocarditis, 444-49, 447t atypical verrucous, 444 bacterial, 445-48 cachectic, 444-45 infective, 445-49 Libman-Sacks, 444 Löeffler’s, 456 marantic, 444-45 nonbacterial thrombotic (NBTE), 444-45 rheumatic, 441 tuberculous, 448 Endocrine system, 791-829 Endodermal sinus tumour, ovary, 748 testis, 711 Endometrial carcinoma, 735-37 Endometrial hyperplasia, 733-34 Endometrioid tumours, ovary, 744-45 Endometriosis, 732-33 Endometritis, 732 tuberculous, 732 Endometrium, 730-38 cyclic changes in, 730, 731f effects of hormones on, 730-31 in menopause, 731 normal structure of, 730 pregnancy changes in, 731 Endomyocardial biopsy, 459 Endomyocardial fibrosis, 456 Endophthalmitis, 508 Endoplasmic reticulum, 24 Endotoxin, 109, 175 Enteric fever, 571-72 Enterochromaffin cells, 561 Enterocolitis, infective, 569-73 ischaemic, 565 membranous, 564-65 necrotising, 565 pseudomembranous, 573 Enteropathy, protein-losing, 576 Environmental chemicals, 242 Environmental diseases, 236-43 Eosinophilia, 141, 350 Eosinophilia, pulmonary, 456, 494 Eosinophilic granuloma, 385 Eosinophils, 141, 350 Eotaxin, 134 Ependyma, 872 Ependymoma, 888-89 Epidermis, structure of, 768-69 Epidermodysplasia verruciformis, 224, 772 Epidermoid carcinoma, 192f cervix, 728-29 lung, 499-500 oesophagus, 541-42 oral cavity, 526-27 penis, 715-16 skin, 783-84 vulva, 723 Epidermolysis bullosa, 522 Epididymitis, 705 Epididymo-orchitis, 705 Epidural haematoma, 882, 883f Epispadias, 714 Epithelioid cells, 152-53 Epithelioid sarcoma, 869 Epstein-Barr virus, 183t, 225, 350, 377, 518 Epulis, 524 Erdheim’s medial degeneration, 36, 407 ER/PR, 765 Erythema marginatum, 443 Erythema multiforme, 777 Erythema nodosum and induratum, 771 Erythema nodosum leprosum (ENL), 160 Erythroblastosis foetalis, 76, 341 Erythrocytic sedimentation rate (ESR), 294 Erythrocytosis, 359 Erythroid series, development of, 287-88 disorders of, 287-326 Erythrophagocytosis, 571 Erythroplasia, 525 Erythroplasia of Queyrat, 715 Erythropoiesis, 287-88 Erythropoietin, 288 Esthesioneuroblastoma, 517 Ethanol, 38, 238-40, 619-21 Euchromatin, 23 Eumycetoma, 182 Evan’s syndrome, 312 Ewing’s sarcoma, 848-49 Ewing’s, James, Exanthemata, viral, 186, 713 Exfoliative cytology (see also under Cytology), 267-77 Exfoliative versus interventional cytology, 267t Exostosis, osteocartilaginous, 843 Exotoxin, 109, 175 Exstrophy (ectopia vesicae), 698 Extracellular fluid compartment, 93 Exudate versus transudate, 96t Exudation, 144 Eye, 507-13 congenital lesions of, 507-08 inflammatory conditions of, 508 metastatic, 513 miscellaneous conditions of, 510-11 normal structure of, 507 tumours and tumour-like lesions of, 511-13, 511t vascular lesions of, 508-10 F Flow cytometry, 18 Fluid compartments, 93 Fluorescent microscope, 14 Fluorochrome, 15 Fluorosis, skeletal, 837 FNAC, 277-83 Foam cell, 160, 397f, Focal glomerulonephritis, 672-74 Focal necrosis, liver, 604-05 Foetal alcohol syndrome, 256 Folate, 253, 304-06 Folin-Wu method, 827 Follicular adenoma, thyroid, 810-11 Follicular hyperplasia, lymph node, 343-44 Folliculitis, 179 Fontana-Masson, 13t, 788 Food poisoning, 181, 572 Foot process disease, 669-70 Fordyce’s granules, 522 Fracture healing, 171-72, 834 Franklin’s disease, 384 Franzen handle, 278f Free radicals, 32 Frost-bite, 242 Frozen section, 10-11 Fungal diseases, 181-83 Fungal infections, 181t lungs, 476-77 skin, 773-74 Fungal stains, 175t, 176f Furuncle, 145, 179 919 G Galactocele, 755 Galactorrhoea, 794 Galen, Claudius, Gallbladder carcinoma, 643-44 Gallstones, 638-41 Gamma glutamyl transpeptidase (g-GT), 595 Gamna-Gandy bodies, 106-07, 108f Ganglion cyst, 855-56 Ganglioneuroma, 801 Gangrene, 49-51 dry versus wet, 51t gas, 59 Gap junctions, 25 Gardner’s syndrome, 585-86 Gartner duct cyst, 723 Gastric acid, 544-45 Gastric analysis, 544-45 Gastric canal, 543 Gastric carcinoma, early (EGC), 556 Gastric lavage, 273 Gastric ulcer, 549-54 benign versus malignant, 557 versus duodenal ulcer, 551t Gastrin, 545 Gastrinoma, 829 Gastritis, 546-49 acute, 546-47 atrophic, 547, 548-49 autoimmune, 547 chronic, 547-49 chronic superficial, 548 classification of, 547 H pylori,547, 548f hypertrophic, 549 type A, 547 INDEX FAB classification, acute leukaemia, 362 myelodysplastic syndrome, 361 Fabricius, Fabry’s disease, 678 Facial clefts, 522 Faecolith, 578 Fallopian tube, 738-39 normal structure of, 738-39 Fallopius, Gabriel, Fallot’s tetralogy, 425 Familial Mediterranean fever, 37 Familial polyposis coli syndrome, 206, 585, 586 Fanconi’s anaemia, 325 Farmer’s lung, 493 FAS receptors, 48, 49f Fascitis, nodular, 862 Fast (combined) smear, 268 Fat aspiration, 88, 282f Fat embolism, 121-22 Fat necrosis, 45-46 breast, 755 Fat-soluble vitamins, 247-51 Fat stains, 12t, 38 Fatty change, 37-39, 621-22 Fatty infiltration, stromal, 39 Fatty liver, 37-39, 621-22 Favism, 316 Felty’s syndrome, 852 Fenton reaction, 32f Fernandez reaction, 159 Ferric-ferrocyanide, 41 Ferrireductase, 295 Ferritin, 300, 301 Ferroportin, 295 Feulgen, Robert, Fever, enteric, 571-72 dengue, 184 viral haemorrhagic, 183-84 yellow, 183-84 Fibril protein, 82-83 Fibrin-split products (FSP), 116, 330, 338 Fibrinogen, 116, 330, 338 Fibrinoid necrosis, 46, 79 Fibrinolysis, 331, 337-38 Fibrinolytic defects, 337 Fibrinolytic system, tests for, 331 Fibroadenoma, breast, 757-58 Fibrocystic change, breast, 755-57 Fibrocystic disease, pancreas, 645 Fibrohistiocytic tumours, 864-65 benign, 864 malignant, 864-65 Fibrolamellar carcinoma, liver, 635-36 Fibroma, ameloblastic, 532 cementifying, 532 chondromyxoid, 845 non-ossifying, 838 oral mucosa, 524 ovary, 749 renal, 694t soft tissue, 861-62 Fibromatosis, colli, 521 desmoid, 863 gingivae, 525 palmar and plantar, 862-63 retroperitoneal, idiopathic, 591 Fibromuscular dysplasia, arteries, 409 Fibronectin, 170 Fibrosarcoma, 863-64 Fibrosclerosis, multifocal, 591, 806 Fibrosis, idiopathic pulmonary, 495-96 Fibrous cortical defect, 838 Fibrous dysplasia of bone, 837-38 Fiedler’s myocarditis, 453 FIGLU test, 308 FIGO classification, cervical cancer, 730t endometrial carcinoma, 737t ovarian carcinoma, 751t vaginal carcinoma, 724t vulval carcinoma, 723t Filariasis, 97, 190 Fine needle aspiration cytology (FNAC), 277-83 advantages of, 278 applications of, 278 complications of, 281 contraindications of, 281 limitations of, 283 method of, 278-79 precautions in, 281 procedure of, 278-79 smear preparation, 279 Fish-mouth appearance, 441 Fissure, anal, 581 Fistula in ano, 581 Fistula, tracheo-oesophageal, 538 Fite-Faraco staining, 157 Fixatives in cytology, 276-77 Flagella, 24 Flavonoids, 254 Flea-bitten kidney, 666, 688 Floppy valve syndrome, 450 920 INDEX type AB, 547 type B, 547 Gastroenteropathy, haemorrhagic, 564-65 Gastrointestinal stromal tumour (GIST), 554-55 Gastrointestinal tract, 538-91 Gaucher’s disease, 262-63 G-cell tumour, 829 Genetic diseases, 256-63 Genetic disorders, 256-63 Genome, human, Germ cell tumours, 193 ovary, 745-48 testis, 709-13 Ghon’s complex, 153-54 GI bleeding, 591t Giant cell lesions of bone, 847-48 Giant cell tumour of bone, 846-48 Giant cell tumour of tendon sheath, 885 Giant cells, 143-44 foreign body, 143 Langhans’, 143 Touton, 143 tumour, 143-44 Gibbs-Donnan equilibrium, 94 Giemsa, 12t, 277 Gigantism, 793-94 Gilbert’s syndrome, 600 Gingivitis, 529 GIST (Gastrointestinal stromal tumour), 554-55 Gitter cells, 872 Glanzman’s disease, 334 Glaucoma, 510-11 Gleason’s staging, prostate, 720 Glial fibrillary acidic protein (GFAP), 24 Glioblastoma multiforme, 887-88 Gliomas, 886-90 Gliosis, 45, 881 Glisson’s capsule, 592 Global, hypoxic-ischaemic encephalopathy, 879-80 Globi, 158f Glomerular basement membrane (GBM), 650, 651f Glomerular diseases, 660-78 classification of, 660t clinical manifestations of, 660-62 contrasting features of, 676t definition of, 660 pathogenesis of, 662-65 specific types of, 665-78 Glomerular filtration rate (GFR), 653 Glomerular injury, pathogenesis of, 662-65 Glomerulonephritis (GN), 665-75 acute, 665-67 chronic, 674-75 crescentic, 667-69 distinguishing features of, 676t end stage, 674-75 focal, 672-74 IgA, 674 mechanisms of, 662-65 membranoproliferative, 671-72 membranous, 669-71 minimal change disease (lipoid nephrosis), 669 necrotising focal, 673 non-streptococcal, 667 oedema in, 661 post-streptococcal, 665-67 primary, 665-75 rapidly progressive, 667-69 secondary, 675-78 Glomerulosclerosis, collapsing sclerosis, 674 diffuse, 677 focal segmental, 673-74 nodular, 678 Glomerulus, structure of, 650 Glomus jugulare tumour, 515 Glomus tumour (glomangioma), 412-13 Glossitis, 523 Glucose tolerance test (GTT), 827f Glucose 6-phosphate dehydrogenase (G6PD) deficiency, 316-17 Glucosuria, 826-27 alimentary (lag storage), 827 renal, 827 Glutathione-S-transferase (GST), 597 Gluten-sensitive enteropathy, 575 Glycocalyx, 21 Glycogen stains, 12t, 40 Glycogen storage diseases, 261-62 Glycogenoses, 261t Glycolipids, 152 Glycophorine, 289 Glycoproteins, adhesive, 170 Glycosaminoglycans, 83, 170, 262 Glycosylated Hb (Hb A1C), 828 Goitre, 807-10 adenomatous, 808-10 colloid, 807-08 diffuse toxic, 806-07 endemic, 807 nodular, 808-10 simple, 807-08 sporadic, 807-08 Goitrogens, 807 Golgi apparatus, 24 Gomori’s methenamine silver, 12t, 175, 176f Gonadoblastoma, ovary, 750 testis, 713 Goodpasture’s syndrome, 494, 667-68 Gout and pseudogout, 853-55 G-proteins, receptors, 26, 212 Grading of tumours, 204-05 Graft rejection, 65-66 Graft versus host reaction, 66 Graft, vascular, 460 Gram Christian, Granular cell myoblastoma, 525, 869 Granular cell tumour, posterior pituitary, 796 Granulation tissue formation, 166-67 Granulocytes, 141, 345 Granuloma, 148-49 annulare, 774 apical, 529 eosinophilic, 385 caseating, 148-49 gravidarum, 412, 524 inguinale, 178-79 lethal midline, 380, 403, 517 non-caseating, 164-85 plasma cell, 384 pyogenicum, 412, 524 reparative, 816, 836 sarcoid, 164-65 spermatic, 705-06 Granulomatous inflammation, 150t actinomycosis, 163-64 examples of, 149-65 leprosy, 157-61 sarcoidosis, 164-65 skin, 774-75 syphilis, 161-63 prostate, 717 tuberculosis, 149-57 uveitis, 508 Granulopoiesis, 345-47 Granulosa cell tumour, ovary, 748-49 testis, 713 Granulosa-theca cell tumour, 749 Graves’ disease, 806-07 Grawitz tumour, 694-96 Grossing, 10 Ground glass nuclei, 813 Growth factors, 210-11 receptors for, 212 Growth, adaptive disorder of, 53-59 Guillain-Barre syndrome, 892 Gum hypertrophy, 363, 524 Gumma, 163f Gynaecomastia, 757 Gynandroblastoma, 749 H 5-Hydroxy tryptamine (HT), 136-37 H-substance, 339 Haber-Weiss reaction, 136 Haemangioblastoma, 414, 889 Haemangioendothelioma, 413-14 Haemangioma, 411-12 capillary type, 411-12 cavernous type, 412 granulation tissue type, 412 liver, 633 mouth, 524 nose, 517 Haemangiopericytoma, 414 Haematemesis, of gastric origin, 554 of oesophageal origin, 539-40 Haematin, 42 Haematocele, 706f Haematogenous spread of tumours, 201-02 Haematological neoplasms, 353-56 classification of, 353-54 etiology, 354-55 pathogenesis, 355-56 Haematological values, 901t Haematoma, 107 dissecting, 407-08 epidural, 882 subdural, 882-83 Haematopoiesis, 284-85 extramedullary, 285, 360 Haematopoietic stem cells, 285-86 Haematoxylin bodies of Gross, 79, 444 Haematuria, 661-62, 691, 696 Haemochromatosis, 42, 627 Haemodialysis-associated amyloid, 86-87 Haemodynamic disturbances, 104-29 Haemoglobin, 292 Haemoglobin disorders, 317-25 Haemoglobinopathies, 317-25 Haemoglobinopathy, unstable, 320 Haemoglobinuria, 311 by repair, 166-67 by second intention (secondary union), 168-69 complications of, 169-70 factors influencing, 170-71 fracture, 171-72 mucosal surfaces, 173 muscle, 172-73 nervous tissues, 172, 891-92 solid epithelial organs, 173 specialised tissues, 171-73 wound, 167-71 Health, definition of, Heart, 417-60 blood supply of, 418 brown atrophy of, 43 cardiac interventions, 459-60 congenital diseases of, 422-26 infarcts, (also see under Myocardial infarction), 429-36 malpositions of, 423 normal structure of, 417-18 transplant, 460 tumours of, 459 Heartburn, 434, 546 Heart failure, 100f, 105f, 419-22 Heart failure cells, 106 Heat-shock protein (HSP), 26 Heavy chain diseases, 384-85 Heberden’s nodes, 851 Heinz body anaemia, 317, 320 Heinz bodies, 311, 317, 320 Helicobacter pylori, 548, 550, 555 Henoch-Schonlein’s purpura, 331 Hepadenoviruses, 226, 606-07 Hepar lobatum, 163 Hepatic arterial obstruction, 604-05 Hepatic coma, 602, 613, 632, 692 Hepatic failure, 602-03 Hepatic tumours and tumour-like lesions, 632-37 Hepatic venous obstruction, 603-04 Hepatisation, lung, 468-70 Hepatitis, clinico-pathological spectrum of, 609-14 activity score, 612-13 acute, 610-11 autoimmune, 611, 629 carrier state, 609-10 chronic, 611-12 chronic active, 612 chronic persistent, 612 contrasting features of, 605 fulminant, 613-14 lupoid, 611 massive to submassive, 613-14 neonatal, 601-02 Hepatitis vaccines, 614 Hepatitis, viral, 605-14 A, 606 B, 606-07 classification of, 605 C, 608-09 D, 607-08 E, 609 G, 609 Hepatoblastoma, 637 Hepatocellular carcinoma, 633-36 Hepatolenticular degeneration, 628 Hepatorenal syndrome, 603 Hepatotoxicity, 617-18 Hephaestin, 295 Hereditary haemorrhagic telangiectasia, 331 Hereditary hyperbilirubinaemia, 600-01 Hereditary persistent of fetal haemoglobin, 322 Hernia, 562-63 hiatus, 538-39 incisional, 170 strangulated, 563 Herpes simplex virus, 186, 773 Herpes virus, 225 Herpes zoster, 186, 773 Herring-bone pattern, 864 Hess capillary test, 329 Heterochromatin, 23 Heterophagy, 37 Heterophile antibody, 352 Heterotopia, 256 Heterotopia, pancreatic, 545, 554 Heterotopic calcification, 51-53 Hexose-monophosphate (HMP) shunt, 289, 317f Heymann’s nephritis, 663-64 Hibernoma, 865 Hidradenoma, 786 vulva, 722 Hippocrates, Hirano bodies, 884 Hirschsprung’s disease, 580 Histamine, 136-37 Histiocytes, 64, 143, 346, 385-86 cardiac, 440 Histiocytic neoplasms, 385-86 Histiocytoma, benign fibrous, 864 malignant fibrous, 864-65 Histiocytosis-X (Langerhans’ cell histiocytosis), 385-86 Histochemistry, 11-13 Histocompatibility leucocyte antigens (HLA), 64-65 Histoplasmosis, 476 HIV, structure of, 68-69 infection, see under AIDS, 67-73 lymphadenopathy, 716 HLA system, 64-65 Hodgkin cells, 370 Hodgkin’s disease, 369-73 classification of, 369 clinical features of, 371-72 etiopathogenesis of, 354-55 morphologic features of, 370-71 other laboratory findings in, 372 prognosis of, 373 staging of, 372 versus non-Hodgkin’s lymphoma, 373t Hodgkin, Thomas, Hollander’s test, 545 Homeostasis, 93-96 Homing receptor, 342 Homogentisic acid, 40-41 Honey-comb lung, 499t Hookah smoking, 237 Hordeolum, 508 Hormones in cancer, 207-08 Hormones, effect on endometrium, 730-31 Hour-glass deformity, 553 Howell-Jolly bodies, 293 H pylori, 176f, 222, 547, 548f, 549f Human genome project, Human herpes virus (HHV), 225, 226, 415 Human immunodeficiency virus (HIV), 67-73 Human leucocyte antigen (HLA), 64-65 921 INDEX cold, 313 march, 313 paroxysmal nocturnal (PNH), 314 Haemoglobinuric nephrosis, 679 Haemolysis, general features of, 310-11 Haemolytic anaemia, see under Anaemias, haemolytic, 310-24 Haemolytic disease of newborn (HDN), 340-41 Haemolytic uraemic syndrome, 331, 334, 689t Haemopericardium, 457 Haemophilia, 335-36 A, 335-36 B, 336 Haemoprotein-derived pigments, 41-43 Haemoptysis, causes of, 502t Haemorrhage, 107-08 intracerebral, 881-82 intracranial, 881-82 pulmonary, 121 subarachnoid, 882 Haemorrhagic diatheses (bleeding disorders), 328-38 coagulation disorders, 335-38 DIC, 337-38 investigations of, 328-31 platelet count disorders, 331-34 platelet function disorders, 334-35 vascular disorders, 331 Haemorrhagic disease of newborn (HDN), 340-41 Haemorrhagic fevers, viral, 183-84 Haemorrhagic gastroenteropathy, 564-65 Haemorrhoids, 581, 632 Haemosiderin, 41-42, 296 Haemosiderosis, 42, 627 Haemostasis, screening tests of, 329-31, 329t Haemostasis, vascular, 331 Haemostatic function, 328-31 Haemostatic disorders, laboratory findings in, 338t Haemothorax, 505 Hageman factor, 139, 320f Hair follicle, tumours of, 785-86 Hairy cell leukaemia, 378-79 Ham’s test, 311, 314 Hamartoma, 193 Hamartoma, pulmonary, 503-04 Hamartomas, vascular, 411 Hamman-Rich syndrome, 496 Hand-Schuller-Christian disease, 385-86 Hansen, GHA, 4, 157 Hapten, 61 Harrison’s sulcus, 249 Hashimoto’s thyroiditis, 804-05 Hashitoxicosis, 805 Hassall’s corpuscle, 388 Hay fever, 493, 515 Hay’s test, 594 Hb Barts’ hydrops foetalis, 321 Hb Constant Spring, 321 Hb D disease, 320 Hb Lepore syndrome, 323 Hb H disease, 321 HBsAg, 607 HBx Ag, 607 hCG, 709, 751-53 HDL, 83, 393-394 Head injury, 882-83 Healing, 165-73 by first intention (primary union), 168 by regeneration, 165-66 922 Human papilloma virus (HPV), 224-25, 270, INDEX 714, 722, 726-27, 771-72 Human T cell lymphotropic virus (HTLV), 68, 227 Hunner’s cystitis, 699 Hunter, John, Hurthle cells, 804-05, 810-11 Hutchinson’s teeth, 163 Hyaline, alcoholic, 35, 621-22 Hyaline change, 35 Hyaline membrane disease, 462-65 Hybridisation, in situ, 17 filter, 17-18 Hybridoma, monoclonal antibodies, 15, 383 polyclonal antibodies, 15, 383 Hydatid disease liver, 187t, 616-17 Hydatid sand, 617 Hydatidiform mole, 751-52 versus choriocarcinoma, 752t Hydrocele, 706 Hydrocephalus, 873-74 Hydrolytic enzymes, 30, 44-45, 348 Hydronephrosis, 692-93 Hydropericardium, 457 Hydropic change, 34-35 Hydrops foetalis, 321 Hydrostatic pressure, 95 Hydrothorax, 505 5-Hydroxytryptamine (5-HT), 137 Hyperadrenalism, 797-98 Hyperaemia, 105-07 active, 105 passive, 105-07 Hyperaldosteronism, 797-98 Hyperbilirubinaemia, 597-601 conjugated, 599-600 hereditary, 600-01 unconjugated, 598 unconjugated versus conjugated, 598t Hypercalcaemia, 53, 816-17 Hypercholesterolaemia, 393-94, 661 familial, 394 Hyperchromatism, 198 Hypercoagulability of blood, 117, 661 Hypereosinophilic syndrome, 494 Hypergastrinaemia, 545 Hyperglycaemia, 818, 821, 827 Hyperinsulinism, 828 Hyperkeratosis, 769 Hyperlipidaemia, 393-94, 661 Hypernephroma, 694-96 Hyperosmolar non-ketotic coma, 825 versus diabetic ketoacidosis, 825t Hyperparathyroidism, 816-17 Hyperphosphataemia, 816, 836 Hyperpigmentation, 40 Hyperpituitarism, 793-94 Hyperplasia, 56-57 atypical, 58 breast, epithelial, 756-57 denture, 524 endometrial, 733-34 focal nodular, liver, 633 microglandular, cervix, 725 prostate, nodular, 717-18 skin, pseudocarcinomatous, 56f, 57, 784 squamous, vulva, 732 thyroid, primary, 806-07 Hyperprolactinaemia, 794 Hypersensitivity reactions, 73-77 delayed type, 77 immediate type, 73-77 Hypersplenism, 387 Hypertension, portal, 630-32 Hypertension, pulmonary, 466-67 Hypertension, systemic, 685-88 atherosclerosis in, 394 classification of, 685t, 686t definition of, 685 effects of, 687-88 etiology, 686-87 in dissecting haematoma, 407 kidney in, 685-88 malignant, 685, 688 pathogenesis of, 686-87 renovascular, 686 Hypertensive heart disease, 437 Hypertensive retinopathy, 509-10 Hypertensive vascular disease, 391, Hyperthermia, 242 Hyperthyroidism, 802-03 Hypertrophic scar, 170 Hypertrophy, 55-56 asymmetric, septal, 454-55 cardiac, 55-56, 420-22 concentric, 421-22 eccentric, 421-22 SER, 37 Hyperuricaemia, 692, 854 Hyperviscosity, 359 Hypervitaminosis A, 248 Hypervitaminosis D, 250 Hyphema, 509f Hypoadrenalism, 798-99 Hypoaldosteronism, 799 Hypocalcaemia, 816, 836 Hypochromasia, 292, 299 Hypoglycaemia, 820, 825, 828 Hypoparathyroidism, 817 Hypopigmentation, 40 Hypopituitarism, 794-95 Hypoplasia, 256 Hypoprothrombinaemia, 337 Hypospadias, 714 Hypothalamus-pituitary axis, 792f hyperfunction of, 794 hypofunction of, 795 Hypothermia, 242 Hypothyroidism, 803-04 Hypoxic cell injury, 29-31 irreversible, 30-31 reversible, 29-30 Hypoxic-ischaemic encephalopathy, 879-80 I Icthyosis, 769-70 Idiopathic pulmonary fibrosis, 495-96 Idiopathic retroperitoneal fibrosis, 591 Idiopathic thrombocytopenic purpura (ITP), 322 IgA nephropathy, 674 Illness, definition of, Image analyser, 19 Immotile cilia syndrome, 484, 705 Immune complex disease, 76-77 kidney, 662-64 Immune complex reaction, 76-77 Immune system, organs of, 61-64 cells of, 61-64 Immunity, diseases of, 66-81 Immunodeficiency diseases, 67-73 Immunodeficiency syndrome, acquired, (AIDS), (also see under AIDS), 67-73 Immunofluorescence, 14 Immunoglobulins, serum, 383, 595, 899 Immunohistochemistry, 15-16 Immunologic lung disease, 493-95 Immunologic tissue injury, 28, 73-77 Immunology of tumours, 228-30 Immunosurveillance of cancer, 228-30 Immunopathology, 62-92 Immunoprophylaxis, hepatitis, 614 Immunotherapy, 230 Impaired glucose tolerance (IGT), 828 Impaired fasting glucose, 826t Impetigo, 771 Implantation cyst, 169 Inborn errors of metabolism, 260-63 Incompetence, valvular, 449-52 Incontinence, pigment, 769 Indian-file arrangement, 761, 762-63 Infarction, 126-29 definition, 126 etiology of, 126 morphology in organs, 126-29 pathogenesis of, 126 types of, 126 Infarcts, border zone, 880 brain, 45, 880-81 cerebral, 880-81 common sites, 127f heart, 429-36 intestine, 563-65 kidney, 127-28 liver, 128-29 lung, 126-27 myocardial, 429-36 retinal, 510 septic, 126, 146f spleen, 128 watershed, 880 Infections, 174-91 pulmonary, Infectious agent, 174 factors relating to, 174-75 identification of, 175t Infectious mononucleosis, 350-52 Infertility, male, 704-05 Infestations, 187t Infiltrations, 37 Inflammation, acute, 130-47 cardinal signs of, 130 causes of, 130 cellular events, 133-36 definition of, 130 factors determining variation in, 144 fate of, 147f fever in, 145 haemodynamic changes in, 130-31 healing, 146 inflammatory cells in, 141-45 leucocytosis in, 145-46 mediators of, 136-40 morphology of, 144-45 regulation of, 140-41 resolution of, 146 signs of, 130 systemic effects of, 145-46 types of, 144 vascular events in, 130-33 effects of, 125-26 etiology of, 124 factors determining, 125 myocardial, 428 Ischaemic bowel disease, 563-65 Ischaemic brain damage, 879-81 Ischaemic heart disease (IHD), 427-37 chronic, 436 coronary atherosclerosis in, 427 effects of, 428 etiopathogenesis of, 427-28 lesions in, 429-37 sudden cardiac death in, 436-37 Islet cell changes in diabetes, 822-23 Islet cell tumours, 828-29 Isochromosome, 259 Isograft, 65 Ito cells, 593, 618 J Jamshidi needle, 286 Janeway’s spots, 448 Jaundice, 42, 596-600 classification of, 597-98 conjugated hyperbilirubinaemia, 599-600 neonatal, 600-01 unconjugated hyperbilirubinaemia, 598 Jaw, lumpy, 163 cysts of, 529-31 Jenner, Edward, Jodbasedow disease, 802 Joints, disease of, 850-56 Joint mice, 851 Joint, normal structure of, 850 Jones’ criteria, revised, 443 Jugular paraganglioma, 515 Junctions, intercellular, 24-25 Juvenile melanoma, 787 Juvenile (retention) polyps, 582-83 Juvenile polyposis syndrome, 586 Juvenile rheumatoid arthritis, 852 Juxtaglomerular apparatus, 650-51 tumour of, 694 K Kallikrein, 140f Kangri cancer, 218, 783 Kaposi’s sarcoma, 225, 226, 415-16 Kartagener’s syndrome, 484, 705 Karyolysis, 30 Karyorrhexis, 30 Karyotypic abnormalities, 257-59 Karyotyping, 257 Kawasaki’s disease, 404 Keloid, 170 Keratoconjunctivitis, 508 Keratohyaline granules, 772 Keratoma, 514-15 Keratomalacia, 247 Keratosis follicularis, 770 Keratosis, solar, 782 Keratosis palmaris et plantaris, 770 Keratosis, smokers’, 525 solar, 782 Kerley lines, 101 Kernicterus, 42, 600-01 Ketoacidosis, diabetic, 825 versus non-ketotic coma, 825t Ketonuria, 827 Kidney, 649-98 adenocarcinoma of, 694-96 biopsy, 652 clearance tests, 653 concentration test, 652-53 congenital malformations of, 656-60 CVC, 107 cystic disease of, 656-60 dilution test, 652-53 end-stage, 674-75 flea-bitten, 666, 688 function tests, 652-53 horse shoe, 656 infarcts, 127-28 large white, 667 normal structure of, 649-52 papilla of, 649, 682 shock, 113, 679 small contracted, 687 stones, 690-92 tumours, 693-98 Kiel classification, 366 Killing, bacterial, 135-36 Kimmelstiel-Wilson lesions, 677-78 Kinin system, 139 Klinefelter syndrome, 258, 704 Knock knee, 249 Knudson two-hit hypothesis, 213 Koch’s bacillus, 149 Koch’s phenomenon, 152 Koch, Robert, KOH preparation, 183 Koilocytosis, 271-72 Korsakoff psychosis, 240, 252 Kraurosis vulvae, 721 Krukenberg tumour, 202-03, 750 Kulchitsky cells, 561 Kupffer cells,143, 593 Kussmaul’s respiration, 104 Kviem test, 165 Kwashiorkor, 246 L Laboratory values of clinical significance, 897-903 Lacis cells, 651 Lactate dehydrogenase (LDH), 30, 434-35 Laennec’s cirrhosis, 622-24 Laennec, RTH, Lambl’s excrescences, 444 Laminin, 170 Landsteiner, Karl, Langerhans’cells, 64, 143, 385-86 Langerhans’cell histiocytosis (histiocytosis-X), 385-86 Langhans’ giant cells, 143, 153 Laryngitis, 519 Larynx, 519-20 carcinoma of, 520 normal structure of, 519 oedema of, 519 papilloma, 519 polyp of, 519 tuberculosis of, 519 tumours of, 519 Laser microdissection, 19 Lateral aberrant thyroid, 812 Lateral vaginal smear, 267t, 268 Lavage, gastric, 273 923 INDEX Inflammation, chronic, 147-65 granulomatous, 149-65, 150t Inflammatory bowel disease, 565-69 Inflammatory cells, 141-44 Inflammatory response, factors determining, 144 Influenza viruses, 184-86 In situ hybridisation, 17 Insecticides, 219t, 242 Insufficiency, valvular, 449-52 aortic, 451 mitral, 450 Insulin metabolism, 819-20 Insulinoma, 826 Insulitis, 822 Integrins, 25, 203 Interferon, 25, 138-39 Interleukin, 25, 138-39 Intermediate filaments, 16, 23-24 Internal environment, 93-94 Interphase, 26 Interstitial cell tumour, testis, 713 Interstitial lung diseases (ILDs), 487t defintion of, 486 with connective tissue diseases, 495 with immunologic lung diseases, 493-95 with smoking, 496 Interstitial tumour, medullary, 694 Intestinal biopsy, 574-76 Intestinal obstruction, 562-63 Intestine, large, 579-90 normal structure of, 579 polyps, 581-86 Intestine, small, 560-71 atresia of, 561 adhesions of, 562 bands of, 562 biopsy, 574 malrotation of, 561 normal structure of, 560-61 obstruction of, 562-63 tumours of, 576-77 Intra-abdominal desmoplastic small cell tumour, 591 Intracellular accumulations, 37-40 of fat, 37-39 of glycogen, 40 of proteins, 39 Intracellular fluid compartment, 93 Intracerebral haemorrhage, 881-82 Intracranial haemorrhage, 881-82 Intraepithelial neoplasia, 207 breast, 760-61 bronchus, 498f cervix, 271-72, 725-28 skin, 782 vulval, 723 Intratubular germ cell neoplasia, 709 Intravascular haemolysis, features of, 311 Intrinsic factor (IF), 303, 308, 545 Intussusception, 563 Inversions, chromosomal, 259 Involucrum, 832 Ionising radiation, 34, 221 Iron cycle, 296f Iron metabolism, 295-96 Irreversibility of shock, 112 Irreversible cell injury, 30-31 Ischaemia, 124-26 brain, 879-81 definition of, 124 924 LE cell phenomenon, 79 INDEX Lead poisoning, 240-41 Lecithin, 639 Leeuwenhoek, von, Legionnaire’s disease, 474 Leiomyoblastoma, 559 Leiomyoma, 737 epithelioid cell, 559 Leiomyosarcoma, 559, 737-38 Leishman, Sir William, Lentigo, 40, 787 Leonardo da Vinci, Lepra reaction, 159-60 Lepromin test, 159 Leprosy, 157-61 bacterial index (BI) in, 158 borderline, 160-61 causative organism of, 157 classification of, 159 clinical features of, 161 histopathology of, 160-61 immunology of, 158-59 incidence of, 158 indeterminate, 161 lepromatous, 160 lepromatous versus tuberculoid, 159t multibacillary, 158 nose, 517 paucibacillary, 158 reactions in, 159-60 Ridley-Jopling classification, 159 Leptocytosis, 293 Leptomeninges, 872 Lesions, definition of, Lethal midline granuloma, 380, 403, 517 Letterer Siwe disease, 386 Leucocytes in health and disease, 347-50 Leucocytoclastic vasculitis, 403, 404 Leucocytosis, 145, 147-51, 348 Leucodema, 522 Leucoderma, 40 Leucodystrophy, progressive multifocal, 878 Leucoerythroblastic reaction, 326 Leucopenia, 347-51 Leukaemias-lymphomas, classifcation of, 353-54 etiology of, 354-55 general aspects, 353-56 pathogenesis of, 355-56 Leukaemia, lymphoid, 354 acute (ALL), 373-74 ALL versus AML, 375t chronic lymphoid (CLL), 375-77 etiology of, 354-55 FAB classification of, 366t hairy cell (HCL), 378-79 pathogenesis of, 355-56 WHO classification of, 368t Leukaemia, myeloid, 354 acute (AML), 362-65 AML versus ALL, 375t chronic myeloid (CML), 357-59 classification of AML, 362t etiology of, 354-55 FAB classification of, 362t pathogenesis of, 355-56 WHO classification of, 357t Leukaemoid reaction, 352-53 lymphoid, 353 myeloid, 353 versus CML, 354 Leukoplakia, 525-26, 714, 721-22 Leukotrienes, 138 Lewis experiment, 134 Lewy bodies, 885 Leydig cell tumour, 713, 749 Leydig cells, 703 Libman-Sack endocarditis, 444-45 Lichen planus, 778-79 Lichen sclerosis et atrophicus, 714, 721-22, 775 Li-Fraumeni syndrome, 213, 759, 860 Ligandin, 597 Line of separation, 49, 50 Lines of Zahn, 117 Linitis plastica, 557, 559f, 560f Lipid cell tumour, ovary, 749-50 Lipiduria, 661 Lipoblast, 866 Lipodystrophy, intestinal, 576 Lipofuscin, 43 Lipogranuloma, 39, 621 Lipoid nephrosis, 669-70 Lipoma, 865-66 Lipooxygenase pathway, 137-38 Lipopolysaccharides, 110 Lipoproteins, 339-40 HDL, 394 LDL, 394 VLDL, 394 Liposarcoma, 866-67 Liver, 592-637 abscess, 614-15 biopsy, 596 chemical and drug injury, 617-18 coagulation disorders, 336-37 CVC, 106-07 fatty change, 37-39, 621-22 metastasis in, 637 normal structure of, 592-93 tumours and tumours-like lesions, 632-37 Liver cell necrosis, types of, 604-05 bridging, 612 piecemeal, 611 Liver function tests, 593-96, 594t Lobar pneumonia, 468-71 Lobule, liver, 592 Lock jaw, 180 Löeffler’s endocarditis, 456 Löeffler’s syndrome, 494 Loose bodies, joints, 851 Lordosis, 249 Ludwig’s angina, 517 Lukes-Collins classification, 366 Lung, 461-504 abscess, 475-76 CVC, 106 fungal infections, 476-77 normal structure of, 461-62 oedema, 100-01 paediatric disease, 462-65 shock, 113 tuberculosis, 155-57 tumours, 496-504 Lupus erythematosus (LE) cell, 79 Lupus nephritis, 80t, 675-77 Lupus vulgaris, 774 Lupus, nose, 517 Luteal phase defect, 732 Lymph nodes, 342-85 metastatic tumours, 385 structure of, 342 Lymphadenitis, reactive, 343-45 acute, 343 chronic, 343-45 Lymphadenopathy, angioimmunoblastic, 344 angiofollicular, 343-44 dermatopathic, 344 HIV-related, 344-45 Lymphangioma, 412, 521 Lymphangiosarcoma, 414 Lymphangitis, 97, 410 Lymphatic obstruction, 97, 410 Lymphatic spread of tumours, 200-01 Lymphatics, 410-11 Lymphoblast, 347 Lymphoblast versus myeloblast, 347t Lymphocytes, 61, 142, 349 atypical, 352 differences between T and B, 62t subpopulations of, 61-64 Lymphocytosis, 142, 179, 349 Lymphoedema, 97, 410, 706 Lymphogranuloma venereum (LGV), 186 Lymphoid hyperplasia, 343-44 angiofollicular, 343-44 follicular, 342 Lymphoid neoplasms, 365-84 classifications, 365-68 general comments, 368-69 Hodgkin’s disease, 369-73 peripheral (mature) B cell malignancies, 374-79 peripheral (mature) T cell malignancies, 379-80 precursor (immature) B and T cell leukaemia-lymphomas, 373-74 Lymphoid series, 347 Lymphokines, 138 Lymphomas, general, 353-56 adult T cell (ATLL), 227-28, 379-80 bowel, Burkitt’s, 225, 377-78 classifications, 353-54, 365-68, 368t CNS, 889 contrasting features of, 373t cutaneous T cell, 379 etiology, 354-55 gut, 559-60 Hodgkin’s, 369-73 nasopharynx, 380 non-Hodgkin’s (NHL), 373-80 pathogenesis, 355-56 staging of, 372t, 380 testis, 713 WHO classification of, 368t Lymphopenia, 349 Lymphopoiesis, 347 Lyon hypothesis, 257 Lysosomal components, 138 Lysosomal storage diseases, 261-62 Lysosomes, 24, 37 changes in, 37 M M-band, 383 MacCallum’s patch, 441 Macrocytes, 292, 306 Macroglossia, 522 Macrophage, alveolar, 106, 143 Macular degeneration, retina, 510 uveal, 512 versus nevus, 788 versus retinoblastoma, 513 Melanosis coli, 40 Membrane attack complex (MAC), 76, 139-40 Membrane damage, cell, 30 Membrane filter, 134 Membranous colitis, 181, 565, 580t Memory cells, 62 MEN syndrome, 206, 829 Mendelian disorders, 259-60 Ménétrier’s disease, 549 Meningioma, 890-91 Meningitis, 874-76 CSF in, 876t Meningocele, 873 Meningomyelocele, 873 Mercury chloride nephropathy, 680 Merkel cells, 769 Mesangial cells, 650 Mesonephroid tumour, ovary, 745 Mesothelioma, 505-06, 591 Metachromasia, 87-88 Metamyelocyte, 345 Metaphyseal fibrous defect, 838 Metaplasia, 57 cartilaginous, 58 bronchus, 57, 498f cervix, 57, 269, 725 columnar, 57 epithelial, 57 intestinal, 57, mesenchymal, 58 oesophagus, 57-58 osseous, 58 squamous, 57, 269, 497 Metastasis, 200-04 biology of, 203-04 haematogenous, 201-02 lymphatic, 200-01 mechanisms of, 203-04 prognostic markers in, 204 retrograde, 201-02 routes of, 200-03 skip, 200 transcoelomic, 202-03 Metastatic calcification, 51, 53 Metatypical carcinoma, 785 Michaelis-Gutmann bodies, 699 Microalbuminuria, 687 Microangiopathy, thrombotic, 689 Microarrays, 7, 19 Microcytes, 292, 299, 323 Microfilaments, 23 Microfilaria, 190 Microglia, 872 Microglossia, 522 Microorganisms, identification of, 175t MicroRNAs in cancer, 216 Microsatellite instability mechanism, 587 Microscopy, basic, 13-14 light, 13-14 electron, 14-15 fluorescent, 14 Microtubules, 24 Microvilli, 23 Mikulicz syndrome, 81, 511 Miliaria, 771 Milk spots, 458-59 Milk-alkali syndrome, 53 Milroy’s disease, 97, 410 Minimal change disease, 669 Mitochondrial changes, 37 Mitosis, 26-27, 165-66 Mitotic counts, 18 Mitotic figures, 198 Mitral stenosis and insufficiency, 450-51 Mitral valve prolapse, 451-52 Mitsuda reaction, 159 Mixed salivary tumour, 534-35 malignant, 537 MMTV, 207, 227, 760 Mole, hydatidiform, 751-53 Molecular genetics, cancer, 208-16 Molecular pathology, 17-18 Molluscum contagiosum, 773 Mönckeberg’s arteriosclerosis, 52, 392 Moniliasis, 182, 270, 723 Monoblast, 346 Monoclonal gammopathy, 380-85 of undetermined significance (MGUS), 384-85 Monoclonal hypothesis, 397 Monoclonality of tumours, 208 Monocyte-macrophage series, 64, 143, 346 Monocytes, 349-50 Monocytosis, 350 Monokines, 139, 143, 346 Mononuclear phagocyte system, 64, 143, 346 Mononucleosis cells, 352 Monosomy, 258 Morphometry, 19 Morgagni, Giovanni, Mostofi classification, 701 M-protein, 383 Mucinous tumours of ovary, 743-44 Mucocele, appendix, 579 gallbladder, 641 oral cavity, 524 sinus, 515 Mucocutaneous syndrome lymph node, 404 Mucoepidermoid carcinoma, 536-37 Mucoid degeneration, 35-36 Mucopolysaccharidoses, 262 Mucormycosis, 176f, 181t Mucoviscidosis, 645 Multifactorial inheritance, 263 Multiple endocrine neoplasia (MEN), 206, 829 Multiple myeloma, 86, 380-84 Multiple (isseminated) sclerosis, 883-84 Mumps, 533 Munro abscess, 778 Muramidase, serum, 364 Muscle, skeletal, diseases of, 856-59 Muscular dystrophies, 858-59 Mushroom-workers’ lung, 494 Mutagenesis, 220, 222-24 Mutations, 208-09, 259-60 Mutator gene, 215 Myasthenia gravis, 857 Mycetoma, 182 Mycobacteria, atypical, 72, 149-51 Mycobacteriosis, 72, 149 Mycobacterium, avium intracellulare, 72, 151 Mycobacterium leprae, 157 Mycobacterium tuberculosis, 72, 149 Mycosides, 152 Mycosis fungoides, 379, 790 Mycosis, superficial, 183, 773-74 925 INDEX Madura foot, 182 Maffucci’s syndrome, 844 Major histocompatibility complex, 64-65 Malabsorption syndrome, 573-76 classification of, 573 Malakoplakia, 699 Malaria, 188-89, 313 Malformations, 256-57 arteriovenous, 413 Malignant melanoma, skin, 787-88 uveal, 512 Malignant peripheral nerve sheath tumour (MPNST), 894-95 Mallasez cells, 529 Mallory hyaline, 35, 621-22 Mallory Weiss syndrome, 540 Malpighi, Marcello, MALT, 61, 142, 342 Malt-workers’ lung, 494 MALToma, 378 small intestine, 576 stomach, 559-60 Mammary duct ectasia, 755 Mammary dysplasia, 755-57 Mantoux test, 152 Maple-bark disease, 494 Mapping, human genome, Marasmus, 245f Marble bone disease, 834 Marek’s disease virus, 225 Marfan syndrome, 36, 331, 407, 451 Margination, 116, 133 Marjolin’s ulcer, 207, 783 Markers in hepatitis B, 607 Masson, Pierre, Mast cells, 136, 141-42, 350 Mastitis, 755 granulomatous, 755 plasma cell, 755 Masugi’s nephritis, 664 Matrix, extracellular, 170 Maturation index (MI), 269t M avium-intracellulare, 72, 151, 155 May-Grunwald, McArdle’s disease, 262 McClintock, Barbara, MCH, 289, 901t MCHC, 289, 901t MCV, 289, 901t Meckel’s diverticulum, 561 Medial calcific sclerosis, 392 Medial necrosis, cystic, Erdheim’s, 36, 407 Mediators of inflammation, 136-40 Medullary sponge kidney, 658-59 Medullary, definition of, 199 Medulloblastoma, 889 Megacolon, 569, 580 Megakaryocyte, 327 Megakaryopoiesis, 327 Megaloblasts, 307 Megamitochondria, 37 Meigs’ syndrome, 505, 749 Meissner’s corpuscle, 769 plexus, 561, 579 Melaena, 554, 591t Melanin, 40 Melanocytic tumours, 787-89 Melanoma, 787-89 oesophagus, 542 skin, 787-89 926 Mycotoxin, 219, 222, 634 INDEX MYC gene, 211t, 212 Myelin figures, 31f Myeloblast, 345 Myeloblast versus lymphoblast, 347t Myelocele, 873 Myelocyte, 345 Myelodysplastic syndrome (MDS), 361-62 FAB classification of, 361 WHO classification, 361 Myelofibrosis, 325-26 Chronic idiopathic, 360-61 Myelogram, 287t Myeloid metaplasia, 360-61 Myeloid neoplasms, 356-65, 357t acute myeloid leukamia, 362-64 chronic idiopathic myelofibrosis, 360-61 chronic myeloid leukaemia, 357-59 essential thrombocytosis, 360 myelodysplastic syndromes, 361-62 polycythaemia vera, 359 Myeloid series, 345-46 Myelolipoma, 800 Myeloma, 380-84 kidney, 382, 684 multiple, 380-84 neuropathy, 382 Myeloma cells, 382f Myeloproliferative disorders, 357-61 Myoblastoma, granular cell, 525, 869 Myocardial blood supply, 418 Myocardial depressant factor (MDF), 112 Myocardial infarction, 429-38 changes in early, 434 chemical and histochemical, 434 changes in, 431-34 clinical features of, 434-35 complications of, 435-36 CK in, 434 diagnosis of, 434-35 ECG changes in, 434 electron microscopic changes in, 434 enzyme determination in, 434-35 etiopathogenesis of, 429-30 gross changes in, 431-33 incidence of, 429 LDH in, 434-35 location of, 430-31 myoglobin in, 435 morphologic features of, 431-33 serum cardiac markers in, 434-35 transmural versus subendocardial, 430t troponins in, 435 types of, 430 Myocardial ischaemia, non-infarct effects of, 429f Myocarditis, 452-54 classification of, 452t Fiedler’s, 453 granulomatous, 453 idiopathic, 453 in connective tissue diseases, 453 infective, 453 miscellaneous types of, 453-54 rheumatic, 441-42 Myofibroblast, 167, 396 Myoglobin, 435 Myometritis, 732 Myometrium, 730-38 normal structure of, 730 Myopathies, 858-59 Myositis ossificans, 869-70 Myxoedema, 803-04 Myxoma heart, 459 Myxoma, odontogenic, 532 Myxomatosis, 226 Myxomatous degeneration of cardiac valves, 451-52 N Naevi, naevocellular, 41f, 787 Naevus sebaceus, 785 Nail-patella syndrome, 678 Nasopharyngeal carcinoma, anaplastic, 225-26, 518-19 Natural killer (NK) cells, 64, 230, 368, 380 Neck, 520-21 cysts of, 520-21 tumours in, 521 Necrosis, 44-46 avascular, bone, 833-34 bridging, 611-12 caseous, 45, 155 centrilobular, haemorrhagic, 106 coagulative, 45 colliquative, 45 cortical, renal, 690 fat, 45-46 fibrinoid, 46 liquefactive, 45 liver cells, 604-05 massive, 613-14 piecemeal, 611 submassive, 613-14 types of, 45-46 versus apoptosis, 48t Necrotising enterocolitis, 181, 565 Necrotising papillitis, 678, 682 Negri bodies, 186 Neonatal hepatitis, 601-02 Neoplasia, (also see under Tumours), 192-235 characteristics of, 194-205 classification of, 193t clinical aspects of, 228-35 definition of, 192 diagnosis of, 232-35 epidemiology of, 205-08 etiology of, 208-28 intraepithelial, 207 pathogenesis of, 208-28 Neoplastic cells, 196-99 Neovascularisation, 167, 199, 215 Nephritic syndrome, 99, 660 versus nephrotic syndrome, 662t Nephritic versus nephrotic oedema, 99t, 662t Nephritis, hereditary, 678 Nephritis, tubulointerstitial, 680-85 Nephroblastoma, 696-98 Nephrocalcinosis, 53f, 684-85, 816 Nephrolithiasis, 690-92 Nephroma, mesoblastic, 694 Nephron, structure of, 649-52 Nephronophthiasis-medullary cystic kidney disease complex, 659 Nephropathy, analgesic (phenacetin abuse), 681t diabetic, 677-78 IgA, 674 lupus, 675-76 mercuric chloride, 680 myeloma, 382, 684 reflux, 682 Nephrosclerosis, 687-89 benign, 687-88 malignant, 688-89 Nephrotic syndrome, 99, 660 versus nephritic syndrome, 662t Nerve sheath tumours, 893-95 Nervous system, 871-95 central, 871-91 healing of, 172, 891-92 normal structure of, 871-72 peripheral, 891-95 Neurilemmoma, 893 versus neurofibroma, 895t Neuroblastoma, 517, 800-01, 886t Neuroendocrine system, 791-829 Neurofibrillary tangles, 884 Neurofibroma, 893-94 plexiform, 894 versus schwannoma, 895t Neurofibromatosis, 206, 893 Neurofibrosarcoma, 894-95 Neurofilaments, 16, 23-24 Neuroglia, 871-72 Neurohypophysis, 793 Neuronophagia, 872 Neuroma, acoustic, 515, 893 traumatic, 893 Neuromuscular diseases, 857-59 Neuropathy, peripheral, 892-93, 826 Neuropeptide, 137 Neuropil, 871 Neurosyphilis, 163 Neutropenia, 141, 348 Neutrophil alkaline phosphatase (NAP), 353, 358 Neutrophilia, 141, 348 Neutrophils, 64, 141, 347-49 toxic granules in, 349f vacuoles in, 349f Nexus, 25 Niacin, 253 Niemann-Pick disease, 262-63 Nissl substance, 871 Nitric oxide mechanism, 139 Nitrosamines, 219, 555 NK cells, 64, 230, 368, 380 Nodular fascitis, 862 Nodule, vocal, 519 Noma, 523 Non-Hodgkin’s lymphomas (NHL), 373-380 adult T cell (ATLL), 379-80 anaplastic large cell (ALCL), 380 Burkitt type, 377-78 CD markers in, 367f classification of, 365-68 etiology of, 354-55 pathogenesis of, 355-56 extranodal, 378 follicular, 377 maltoma, 378 marginal zone, 378 mycosis fungoides, 379-80 mantle cell, 378 mature B cell type, 374-79 mature T cell type, 379-80 monocytoid, 379 periperal B cell type, 374-79 peripheral T cell type, 379-80 precursor B and T cell type, 377-78 splenic margina;l zone, 379 SLL/CLL, 375-77 staging of, 380 versus Hodgkin’s disease, 373t working formulations for clinical usage, 366 WHO classification, 367-68, 368t Noncirrhotic portal fibrosis, 629-30 Nondisjunction, 258 Nonossifying fibroma, 838-39 Normal values, 896-903 in clinical chemistry, 898-900 in haematology, 901-03 other body fluids, 900-01 weights and measurements of organs, 896-97 Normoblastaemia, 292 Normoblasts, 287-88 Nose and paranasal sinuses, 515-17 carcinoma of, 517 inflammatory conditions of, 515-17 normal structure of, 515 tumours of, 517 Notochord, 849 Nucleocytoplasmic ratio, 197-98, 271 Nucleolar organiser regions (NORs), 198 Nucleolus, 23 Nucleotides, 23 Nucleus, structure of, 22-23 Nutmeg liver, 106-07 Nutritional diseases, of brain, 886 O Osteosarcoma, 841-43 central, 841-43 central versus surface, 844t juxtacortical, 843 medullary, 841-43 surface, 843 periosteal, 843 parosteal, 843 telangiectatic, 842 Otitis media, 514 Otic polyp, 514 Otosclerosis, 514 Ovalocytosis, 315 Ovarian tumours, 740-51 clinical features of, 741 classification of, 742t etiopathogenesis of, 740-41 germ cells, 745-48 metastatic, 750 miscellaneous, 749-50 sex cord stromal, 748-49 staging of, 751t surface epithelial, 741-45 Ovary, 739-51 non-neoplastic cysts of, 740 normal structure of, 739-40 tumours of, 740-51 Overhydration, 102-03 Overinflation, lung, 482-83 Oxygen dissociation, 290f Oxygen-derived radicals, 31-33, 139 Ozone, 236 927 P Paan, in oral cancer, 206 Pacinian corpuscles, 769 P-component, 83, 88 Paediatric diseases, 263-65 Paediatric lung disease, 462-65 Paediatric tumours, 206-07, 263-64 Paget’s disease, of bone, 837 of nipple, 764-65 of vulva, 722 Pancarditis, rheumatic, 440-42 Pancoast’s syndrome, 502 Pancreas, 644-48 carcinoma, 647-48 cystic fibrosis of, 645 endocrine, 818-29 exocrine, 644-48 fat necrosis of, 45-46 heterotopia, 545 normal structure of, 644-45 pseudocyst of, 647 Pancreatitis, 646-48 acute, 646 chronic, 646-47 Pancytopenia, 325t Panhypopituitarism, 794-95 Panniculitis, 771 Pannus formation, 852 Papanicolaou, George, 5, 266 Papanicolaou’s (Pap) smear, 268-72, 275-76 stain, 277 Papillitis, necrotising (papillary necrosis), 678, 683 Papilloedema, 511 INDEX Oat cell carcinoma, lung, 500 Obesity, 243-44 Occupational lung diseases (also see under Pneumoconiosis), 43, 487-93 Ochronosis, 40-41 Odontogenic tumours, 531-32 Odontomas, 532 Oedema, 96-102 angioneurotic, 76, 97, 770 cardiac, 99-100 cerebral, 101-02 definition and types of, 96 dependent, 99 hepatic, 102 high altitude, 101 inflammatory, 97 morphology of, 99-102 nephritic, 99, 660 nephrotic, 99,660 nephritic versus nephritic, 99t pathogenesis of, 96-99 pitting versus non-pitting, 99 postural, 97 pulmonary, 100-01 nutritional, 102 renal, 99 Oesophagitis, 540-41 Barrett’s, 540-41 infective, 541 reflux (peptic), 540 Oesophagus, 538-43 atresia of, 538 cancer, 541-43 congenital anomalies of, 538 diverticula of, 539 muscular dysfunctions of, 538-39 normal structure of, 538 rings of, 539 rupture of, 540 tumours of, 541-43 varices, 539-40 webs of, 539 Oestrogen, 207, 731 Oligodendrocytes, 872 Oligodendroglioma, 882 Oliguria, 654, 679f Ollier’s disease, 844 Omega-3 fatty acids, 394 Oncocytoma, 37, 535-36, 694 Oncofoetal antigens, 234, 709 Oncogenes, 209-12 versus anti-oncogenes, 214 Oncogenesis, (also see under Carcinogenesis), 208-28 Oncogenic viruses, 222-28 DNA, 224t RNA, 227t Oncology, 192 Oncomirs in cancer, 216 Oncotic pressure, 95, 96-97 Ontogenesis, 264 Opportunistic infections, 72f, 181, 449, 523t Opsonins, 135 Opsonisation, 135 Oral soft tissues, 522-27 developmental anomalies of, 522 normal structure of, 522 tumours of, 523-27 white lesions of, 522 Orchitis, 705 granulomatous, 705 tuberculous, 705 Organelles, 23-24 Organoid pattern, 814 Ormond’s disease, 591 Osler’s nodes, 448 Osler-Weber-Rendu disease, 331, 525, 860 Osmolality, 94 Osmolarity, 94 Osmotic fragility, 315, 324 Osmotic pressure, 95 colloid, 95 crystalloid, 95 Ossification, 839 Osteitis deformans, 837 Osteitis fibrosa cystica, 835-36 Osteoarthritis, 850-51 Osteoblast, 830 Osteoblastic tumours, 840-43 Osteoblastoma, 841 Osteochondroma, 843-44 Osteoclastoma, 846-48 Osteocyte, 830 Osteodystrophy, renal, 836-37 Osteogenesis, 831,842 Osteogenesis imperfecta, 834 Osteoid osteoma, 841 Osteoma, 841 Osteomalacia, 250 Osteomyelitis, 831-33 pyogenic, 831-33 tuberculous, 833 Osteonecrosis, 833-34 Osteopetrosis, 834 Osteophytes, 851 Osteoporosis, 835 928 Papilloma, 193t INDEX breast, intraductal, 759 choroid plexus, 889 juvenile, 224 larynx, 519 mouth, 524 nose and paranasal sinuses, 517 skin, 780 urinary bladder, 701 Papilloma viruses, 224-25 Papillomatosis, florid, 224, 757 Papovaviruses, 224-25 Pappenheimer bodies, 300 Paradoxical embolus, 119 Paraganglioma, extra-adrenal, 801 Parakeratosis, 769 Paranasal sinuses, 515-17 Paraneoplastic syndrome (PNS), 231-32, 502 Paraphimosis, 714 Paraproteinaemias, 380-85 Parasitic diseases, 187-91 Parasitism, 174 Parathormone, 816 Parathyroid gland, 815-18 normal structure of, 815-16 tumours of, 817-18 Parkinsonism, 884-85 Paronychia, 182 Paroxysmal cold haemoglobinuria (PCH), 313 Paroxysmal nocturnal haemoglobinuria (PNH), 314 Partial thromboplastin time with kaolin (PTTK), 330 Pasteur, Louis, Patent ductus arteriosus (PDA), 424 Patent truncus arteriosus, 425 Pathology, definition of, evolution of, 1-7 history of, 1-7 subdivisions of, 7-8 Paul-Bunnel test, 352 Pavementing, 116, 133 Pelger-Huet anomaly, 349 Pellagra, 253 Pelvic inflammatory disease (PID), 738-39 Pelvis, kidney, 649 tumours of, 700-02 Pelviureteric junction (PUJ) obstruction, 690t, 692 Pemphigoid, 777 Pemphigus, 776-77 Penis, 714-16 carcinoma of, 715-16 normal structure of, 715 Pepsin, 545 Peptic ulcer, 549-54 acute (stress), 550 benign versus malignant, 557 chronic duodenal versus gastric, 551 duodenal, 550-54 gastric, 550-54 Pericardial fluid accumulations, 456-57 Pericardial plaques, 458-59 Pericarditis, 457-59 Periodontal disease, 529 Periodontal tissue, normal structure of, 527-28 Peritoneal bands and adhesions, 562-63 Peritoneum, 590-91 tumors, 591 Peritonitis, 590-91 Permeability factors, 136-40 Permeability, vascular, 131-33 Pertussis, 178 Petechiae, 107, 329, 331 Peutz-Jeghers syndrome, 582 Peyronie’s disease, 170 p53 gene, 213 pH of blood, abnormalities of, 103-04 Phagocytes, 64, 143 Phagocytosis, 64, 134-36, 143 Phagolysosome, 135f Phagosome, 135f Pharynx, 517-19 Phase reactant proteins, 83, 140 Pheochromocytoma, 79-800 Philadelphia chromosome, 199, 353, 355, 356f, 358 Phimosis and paraphimosis, 714 Phlebothrombosis, 409 Phlebotomy, 359 Phlegmasia, 410 Phocomelia, 256 Phosphatidylserine, 48 Phthisis bulbi, 510 Phyllodes tumour, 758-59 Physaliphorous cells, 849 Physical carcinogenesis, 220-22 Physical injury, 28, 34, 242-43 Pica, 298 Pickwickian syndrome, 244-45 Pigmented villonodular synovitis, 855 Pigments, 40-44 malarial, 42 wear and tear, 43 Piles, 581 Pilomatricoma, 785 Pinguecula, 510 Pinocytosis, 143 Pituitary gland, 792- 96 normal structure of, 792-93 tumours of, 795-96 Placenta, 751-53 normal structure of, 751 Plague, 175-77 Plaque, bacterial, 528 Plaque, pericardial, 458-59 Plaques, atheromatous, 398-99 Plasma cell, 63, 142-43, 349, 380 granuloma, 384 Plasma cells, disorders of, 380-84 Plasmacytoma, localised, 384 Plasmacytosis, reactive, 382 Plasmin, 116f, 139, 141f, 330f Platelet, 327-28 activating factor (PAF), 138 adhesion, 115, 328 aggregation, 115, 328 release reaction, 115, 327 tests for, 329 Pleomorphic adenoma, salivary gland, 534-35 Pleomorphism, 197 Pleura, 504-06 tumours of, 505-06 Pleuritis, (pleurisy), 504-05 Plummer-Vinson syndrome, 298, 526, 539, 541 Pneumoconiosis, 487-93 asbestos disease, 492-93 berylliosis, 493 Caplan, 490 classification of, 488t coal-workers’, 488 rheumatoid, 490 silicosis, 490-91 Pneumocytes, 461-62 Pneumonia, 467-75 aspiration, 474-75 atypical, 472-74 bacterial, 468-71 broncho (lobular), 471-72 caseous, 156 classification of, 468t hypostatic, 475 Legionella, 474 lipid, 475 lobar, 468-71 lobar versus bronchopneumonia, 473t lobular, 471-72 pathogenesis of, 467-68 Pneumocystis carinii, 474 primary atypical, 472-74 viral and mycoplasmal, 472-74 Pneumonitis, 467-75 allergic, 493-94 hypersensitivity, 493-94 interstitial, 472-74 rheumatic, 443 Pneumothorax, 505 Podocytes, 650, 669 Poikilocytosis, 292 Poisoning, aluminium phosphide, 242 carbon monoxide, 241 cyanide, 242 lead, 240-41 mercuric chloride, 680 organophosphate, 242 Pollutants, 236-37 Polyarteritis nodosa (PAN), 402 Polyarthritis, 442-43, 851 migratory, 442-43 Polychondritis, relapsing, 514 Polychromasia, 292 Polyclonal, 15, 383 Polycystic kidney disease, 657-58 adult, 657-58 infantile, 658 Polycystic ovary disease, 740 Polycythaemia vera, 359 Polyembryoma, 711, 742t Polyglandular autoimmune syndromes, 829 Polymerase chain reaction (PCR), 6, 18 Polymorphonuclear neutrophils (PMN), 64, 141, 347-49 Polymyositis-dermatomyositis, 81, 495 Polyol mechanism in diabetes, 825 Polyoma virus, 225 Polyploidy, 258 Polyps, adenomatous, 584 antrochoanal, 515-16 aural, 514 cervical, 725 colorectal, 582-86 endometrial, 735 fibroepithelial, 722, 780 gastric, 554 hamartomatous, 554, 582 hyperplastic, 554, 582 inflammatory, 583 juvenile, 582, 586 lymphoid, 583 retention, 582 Pseudocartilage, 535 Pseudocyst of pancreas, 647 Pseudogout, 855 Pseudolymphoma, 81, 560 Pseudomembrane, 181, 565 Pseudomembranous inflammation, 144 Pseudomyxoma peritonei, 203, 579, 743 Pseudopolyp, 568 Pseudotumour, inflammatory, 511 Pseudoxanthoma elasticum, 31 Psoriasis, 778-79 PTEN gene, 759, 787 Pterygium, 510 Ptyalism, 533 Pulmonary embolism, 120-21 Pulmonary eosinophilia, 456, 494 Pulmonary fibrosis, idiopathic, 495-96 Pulmonary hypertension, 466-67 Pulmonary oedema, 100-01 Pulmonary tuberculosis (see under Tuberculosis), 149-57 Pulmonary valve, atresia, 426 stenosis, 426 Pulpitis, 529 Pulseless disease, 404 Punctate basophilia, 292 Pure red cell aplasia, 326 Purines, 23 Purpura, 107, 331-34 Henoch-Schonlein, 331 idiopathic thrombocytopenic (ITP), 332-34 thrombotic thrombocytopenic (TTP), 334 Pus, 145 Putrefaction, 49 Pyaemia, 145 Pyelitis, 681 Pyelonephritis, 680-84 acute, 680-82 chronic, 682-84 diabetic, 678 obstructive, 682 tuberculous, 684 xanthogranulomatous, 683 Pyknosis, 30 Pyknotic index, 269 Pyloric stenosis, 546 Pyogenic granuloma, 412, 524 Pyonephrosis, 682 Pyorrhoea, 529 Pyridoxine, 253 Pyruvate kinase (PK) deficiency, 317 Q Quality control in histopathology, 11 Quick’s one stage method, 330 Quinacrine banding, 257 Quinsy, 518 R Rabies, 186 Rachitic rosary, 249 Radiation carcinogenesis, 34, 220-22, 242 Radicals, free, 31-33, 139 Radioautography, 18 Radiolysis, 34f Ranula, 524 Rappaport classification, 365 RAS gene, 210-11 Ray fungus, 164 Raynaud’s disease and phenomenon, 405 RB gene, 213 REAL classification, 366-67 Recessive inheritance, 260 Red blood cells, 287-326 Red cell membrane, 289 hereditary abnormalities of, 314-15 Red line response, 131 Reed-Sternberg (RS) cell, 369-70 Reflux nephropathy, 682 Regeneration, 165-66 Regurgitation, valvular, 449-51 Reid index, 478 Reidel’s struma, 805-06 Reinke’s crystals, 703 Reiter’s syndrome, 81-82, 699 Rejection reactions, 65-66 Renal cell carcinoma, 694-96 Renal clearance tests, 653 Renal cortical necrosis, 690 Renal cysts (also see under Cysts, kidney), 656-60 Renal dysplasia, 657 Renal failure, 653-56 acute (ARF), 654 chronic (CRF), 654-56 Renal function tests, 652-53 Renal osteodystrophy, 836-37 Renal pelvis, tumours of, 702 Renal vascular disease, 685-90 Renin-angiotensin-aldosterone mechanism, 98, 686-87, 796 Reninoma, 694 Repair, 166-73 Reperfusion injury, 31-33 in myocardial infarction, 433 Residual bodies, 24, 43 Resistance, 66 Respiratory burst, 135 Respiratory distress syndrome (RDS), 462-65 adult, 462-65 neonatal, 462-65 Respiratory syncytial virus (RSV), 472 Response-to-injury hypothesis, 395-97 Reticulocyte, 288 Reticuloendothelial system (RES), 64, 143 Retinal detachment, 510 Retinitis pigmentosa, 507 Retinoblastoma, 512-13 versus malignant melanoma, 513t Retinol, 247-48 Retinopathy, diabetic, 508-09, 826 hypertensive, 509-10 prematurity, 507 Retrolental fibroplasia, 507 Retroperitoneal fibromatosis, 591 Retroviruses, 183, 227-28 Reversible cell injury, 29-30 morphology of, 34-36 Reye’s syndrome, 38, 602 Rhabdomyoma, 455, 867 Rhabdomyosarcoma, 867-68 embryonal, 867 Rhesus system, 339 Rheumatic fever and RHD, 438-44 acute stage, 440 cardiac lesions in, 439-42 causes of death in, 443-44 chronic stage, 441 clinical features of, 443-44 929 INDEX nasal, 515-16 neoplastic, colorectal, 583-85 Peutz Jeghers, 582 stomach, 554 stromal, 722, 780 Polyribosomes, 24 Polyserositis, 458 Pompe’s disease, 262 Porcelain gallbladder, 642 Pores of Kohn, 462 Porphyria, 42-43 Porphyrins, 42-43 Porta hepatitis, 592 Portal hypertension, 630-32 Portal venous obstruction, 604 Portwine stain, 411 Post-myocardial infarction syndrome, 436 Pott’s disease, 833 Pott, Sir Percival, Poxviruses, 186, 226 PPD test, 152 Precocious puberty, 794, 838 Predisposing factors in tumours, 205-08 Pregnancy tumour, 412, 524 Preleukaemic syndrome, 361-62 Premalignant lesions, 207 Pre-proinsulin, 819 Pressure gradients, 94-95 Primary complex, 153-55 Primitive neuroectodermal tumour (PNET), 836t Prinzmetal’s angina, 429 Prion proteins, 83, 174, 878 Probe, 17, 18 Procallus, 171-72 Proerythroblast, 287 Progeria, 60 Progestrogen, 208, 731 Progressive massive fibrosis, 489-90 Progressive multifocal leucoencephalopathy (PML), 878 Progressive systemic sclerosis, 80-81 Proinsulin, 819 Prolapse, mitral valve, 451-52 Promyelocyte, 345 Pronormoblast, 287 Properdin, 664 Prostacyclin, 137 Prostaglandins, 137 Prostate, 716-20 acid phosphatase (PAP), 720 carcinoma, 718-20 cytology of, intraepithelial neoplasia (PIN), 719 nodular hyperplasia, 717-18 normal structure of, 716-17 specific antigen (PSA), 720 Prostatitis, 716-17 granulomatous, 717 Protease inhibitor, 479-80, 628 Protease-antiprotease hypothesis, 479-80 Protein, serum, 595 Protein-energy malnutrition (PEM), 245-46 Proteinuria, 99t, 652, 660-61 highly selective, 660, 669 non-selective, 660, 671 Proteoglycans, 83, 170, 262 Prothrombin time, 330 Prothrombotic factors, 114 Prussian blue reaction, 13t, 41, 301 Psammoma bodies, 52, 813, 890 930 definition of, 438 endocarditis, 441 etiopathogenesis of, 438-39 extra-cardiac lesions in, 442-43 incidence of, 438 morphologic features of, 439-43 myocarditis in, 441-42 pericarditis in, 442 pleuritis, 443 pneumonitis, 443 stigmata of, 443 valvulitis in, 440-41 vasculitis in, 443 vegetations in, 441, 442f, 447t Rheumatoid arthritis, 78t, 851-53 Rheumatoid factor, 851 Rheumatoid nodules, 852 Rheumatoid pneumoconiosis, 490 Rheumatoid spondylitis, 853 Rhinitis, 515 Rhinoscleroma, 516 Rhinosporidiosis, 181t, 516 Riboflavin, 253 Ribosomes, 24 Rickets, 249 Ridley-Jopling classification, 159 Ring chromosome, 259f RNA oncogenic viruses, 227t Rodent ulcer, 784-85 Rokitansky’s protuberance, 746 Rokitansky, Carl F, Rokitansky-Aschoff sinus, 642 Romanowsky, DL, Rosettes, 62t Rotor’s syndrome, 601 Rouleaux formation, 382 Round cell tumours, 848, 861 RS cell marker, 369, 371f Russell bodies, 35, 382 Rye classification, 371 INDEX S Sacrococcygeal teratoma, 264t Saddle nose deformity, 163 Saddle thrombus, 120 Salah bone marrow needle, 287f Salivary glands, 533-37 normal structure of, 533 tumours of, 534-37 tumours of minor, 534t Salmonellosis, 176t, 572 Salpingitis, 738-39 tuberculous, 739 Salt deficiency, 103t Saponification, 46 Saprophytism, 174 Sarcoidosis, 164-65 Sarcoma, botryoides, 519, 724, 867, 868f Sarcoma, definition of, 192 SARS, 185 Scab, 169 Scar, hypertrophic, 170 Schaumann bodies, 165 Schiller Duval body, 748 Schiller’s test, 727 Schilling test, 308, 545,901t Schistocytosis, 293 Schistosomiasis, 222, 700, 722 Schwann FT, Schwannoma, 893-95 acoustic, 515, 893 versus neurofibroma, 895t Scirrhous tumours, 199, 557, 762 Scleroderma (systemic sclerosis), 80-81 Sclerosing adenosis, breast, 757 Scotomas, 509 Scurvy, 251-52 Sebaceous gland tumours, 785-86 Seborrheic keratosis, 780, 781f Seed-soil theory, 201 Selectin, 25, 134 Semen examination, 703, 900t Seminoma, spermatocytic, 710 Seminoma, classic, 709-10 Senile keratosis, 782 Senile plaques, 87, 884 Sentinel lymph node, 765 Septicaemia, 145 Sequestration, bronchopulmonary, 462 Sequestrum, 832 Serotonin, 137 Serous tumours of ovary, 742-43 Sertoli cell tumour, 713, 749 Severe acute respiratory syndrome (SARS), 185 Sex chromatin, 23, 257f, 275 Sex chromosomes, 23, 257 Sex cord-stromal tumours, ovary, 748-39 testis, 713 Sezary syndrome, 379, 790 Sheehan’s syndrome, 794 Shift-to-left, 348, 353 Shift-to-right, 307, 348-49 Shigella, disentery, 176t, 572 Shingles, 185, 773 Shock, 108-13 adrenal in, 113 anaphylactic, 73, 109 brain in, 112-13 cardiogenic, 109, 110 clinical features of, 113 compensated (reversible), 111-12 complications of, 113 decompensated (irreversible), 112-13 definition of, 108 etiology and classification of, 109 hypovolaemic, 109 inflammatory mediators of, 111f kidney in, 113 lungs in, 113 morphologic features in, 112-13 neurogenic, 109 pathogenesis of, 109-11 septic, 109, 110-11 stages of, 111-12 true, 108 Shock, kidney, 113, 679 Shock, lung, 113 Shunts, heart, 423-26 left to right, 423-24 right to left, 424-26 Sialadenitis, 533-34 Sialolithiasis, 533 Sialorrhoea, 533 Sicca syndrome, 81, 533 Sickle cell syndrome, 318-19 Sideroblasts, 300-01 ring, 300f Siderocytes, 301 Siderofibrotic nodule, 106-07, 108f Siderosis, 42, 627 Sigmoid curve, 289 Signal transduction proteins, 212, 216f Signet ring carcinoma, 557, 560f Silicosis, 490-91 Silo-filler’s disease, 494 Simmond’s syndrome, 794 Simple cyst, bone, 839-40 Single gene defect, 259-60 Sinus histiocytosis, 344 Sinusitis, 515 Sipple syndrome, 829 Sjögren’s syndrome, 81, 533 Skeletal muscles, structure of, 856-57 tumours, 867-68 Skeletal system, 830-56 Skin, 768-90 dermatoses, 769-79 normal structure of, 768-69 tumours of, 779-90 Slow releasing substance of anaphylaxis (SRS-A), 137 Slow transforming viruses, 227 Sludge, biliary, 639f Small cell carcinoma lung, 500-01 versus non-small cell carcinoma, 500t Small cell tumour, desmoplastic, 591 Smog, 236 Smoking, 218, 237, 480f, 497-98 passive, 237 Sodium and water, 94, 687 deficiency of, 103 retention of, 97 Soft tissue tumours, 860-70 classification of, 860 diagnostic criteria of, 860-61 etiology and pathogenesis of, 860 general features of, 860 staging and grading of, 861 Solar keratosis, 782 Soldiers’ spots, 459 Solitary cyst, bone, 839-40 Solitary rectal ulcer syndrome, 581 Somogyi effect, 825 Sorbitol mechanism, 824-25 Southern blot, 17 Special stains, 11-13 Spectrin, 289, 314-15 Speech recognition system, 19 Spermatic granuloma, 705-06 Spherocytosis, 314-15 Spina bifida, 256, 873 Spinal cord defects, 256, 873 Spiradenoma, 786 Spleen, 386-88 CVC of, 106 normal structure of, 386 Splenectomy, effects of, 387-88 Splenic rupture, 388 Splenic tumour, acute, 388 Splenitis, 388 Splenomegaly, 387t congestive, 387 Splenosis, 388 Spondylitis, 853 Spongiform encephalopathy, 878 Spongiosis, 769 Spread of tumours, 200-03 Sprue, 575 Sputum examination, 272, 275-76 Squamocolumnar junction, 724 Sydney classification, gastritis, 548 Symbiosis, 174 Sympathetic ophthalmia, 508 Sympathicoblastoma, 800 Synovial sarcoma, 868-69 Synovioma, benign, 855 Synovitis, villonodular, 855 Syphilis, 161-63 aortitis, 401 cardiovascular, 163 causative organisms of, 161 congenital, 163 immunology of, 161-62 mode of transmission of, 162 nose, 163 primary, 162 secondary, 162 stages of, 162-63 tertiary, 162-63 Syphilitic aortitis versus aortic atheroma, 402t Syringobulbia, 873 Syringomyelia, 873 Syringomyelocele, 873 Syrinx, 873 Systemic lupus erythematosus (SLE), 78-80, 495, 675-77 heart in, 444 Systemic sclerosis, 80-81, 495 T Tabes dorsalis, 163 Tabes mesenterica, 154, 570 Takayasu’s arteritis, 404 Tamm-Horsfall protein, 382, 652 Target cell, 293 Tart cell, 79 Tattooing, 44 Teare’s disease, 454-55 Teeth, normal structure of, 527-28 Telepathology, 19-20 Telomerase, 215 Telomere, 59 Tenascin, 170 Tenosynovitis, nodular, 855 Teratogens, 256 Teratology, 256 Teratoma, of ovary, 746-47 of testis, 711-12 sacrococcygeal, 264t Testicular tumours, 706-13 Testis, 703-13 normal structure of, 703 torsion of, 706 tumours of, 706-13 Tetanus, 180 Tetralogy of Fallot, 425 Thalassaemias, 320-24 alpha, 321 anaemia in, 320 beta, 322-24 classification of, 321t definition of, 320 Thalidomide malformations, 256 Thecoma, 749 Thermal injury, 34, 242 Thiamine, 252 Thioflavin, 88 Thrombasthenia, 334 Thrombin time, 320, 329t Thromboangiitis obliterans (Buerger’s disease), 404 Thrombocytopenias, 332-34 drug-induced, 332-34 heparin-induced, 332 immune, 332-34 thrombotic, 334 Thrombocytosis, 334 essential, 360 Thromboembolism, 120-21, 435 Thrombogenesis, 114-17 Thrombogenic theory, 395 Thrombolytic therapy, 433 Thrombomodulin, 114 Thrombophlebitis, 409-10 migrans, 410 Thrombopoiesis, 327-28 Thrombopoietin, 327 Thrombosis, 113-19, clinical effects of, 119 coronary, 430 definition of, 113-14 fate of, 118-19 morphology of, 117-18 pathophysiology of, 114-17 predisposing factors in, 117 Thrombospondin, 328 Thrombotic microangiopathy, 689 Thrombotic thrombocytopenic, purpura (TTP), 334 Thromboxane, 137 Thrombus, 113 antemortem versus postmortem, 118t arterial versus venous, 118t ball valve, 118 morphology of, 117-18 Thrush, oral, 182, 523 Thymocytes, 388 Thymoma, 388-89 Thymus, 388-89 Thyroglossal cyst, 520 Thyroid cancer, 811-15 etiolopathogenesis of, 812 follicular, 813 medullary, 813-14 papillary, 812-13 undifferentiated (anaplastic), 814-15 Thyroid gland, 801-15 function tests, 802 functional disorders of, 802-04 normal structure of, 801-02 tumours of, 810-15 Thyroiditis, 804-06 autoimmune, 804-05 deQuervain’s, 805 granulomatous, 805 Hashimoto’s, 804-05 infectious, 805 lymphocytic, 805 Riedel’s, 805-06 Thyrotoxicosis (hyperthyroidism), 802-03 Tinea, 773-74 Tissue tension, 95 TNM staging, 205, 861 Tobacco smoking, 218, 237, 480f, 497-98 Tocoferol, 250-51 Tolerance, immune, 77 Tongue, lesions of, 522-23 Tonsillitis, 517-18 Tooth, 527-32 diseases of, 528-32 normal structure of, 527-28 931 INDEX Squamous cell carcinoma, 192f cervix, 728-29 lung, 499-500 oesophagus, 541-42 oral cavity, 526-27 penis, 715-16 skin, 783-84 vulva, 723 Squamous intraepithelial lesions (SIL), H-SIL, 271 L-SIL, 271 Squamous metaplasia, 57, 269, 497 Staghorn stone, 691 Staging of tumours, 205, 861 AJC, 205, 861 Enneking’s, 861 TNM, 205, 861 Staphylococcal infections, 179-80 Starling’s hypothesis, 420 Starvation, 245 Stasis, vascular, 131 Steatocystoma multiplex, 782 Steatohepatitis, alcoholic, 37-39, 621-22 non-alcoholic (NASH), 629 Steatorrhea, 574 Steatosis, 37-39, 621-22 Stein-Leventhal syndrome, 740 Stem cells, haematopoietic, 285 Stem cell research, Stenosis, valvular, 425-26, 449-51 aortic, 426, 450-51 mitral, 449-50 pulmonary, 426 tricuspid, 425-26 Stevens-Johnson syndrome, 522, 777 Stitch abscess, 168 Stomach, 543-60 acute dilatation of, 546 cancer of, 555-60 normal structure of, 543-44 rupture of, 546 tumours and tumour-like lesions of, 554-60 Stomatitis, 522-23 Stomatocytosis, 316 stomatin in, 316 Stones, gallbladder, 638-41 Stones, kidney, 690-92 Storage diseases, 260-63 neuronal, 885 Storage iron, 295 Storiform pattern, 860, 864-65 Stout, AP, Streptococcal infections, 180-81 Stroke syndrome, 400, 879 Stromal fatty infiltration, 39 Struma ovarii, 747 Struvite (staghorn) stone, 691 Sty, 508 Subarachnoid haemorrhage, 882 Subependymoma, 889 Sudden cardiac death, 429f, 436-37 Sulfur granules, 164 Suppuration, 145 Surfactant, 462 Surgical pathology, protocol, 9-11 Sushruta, Suture tracks, 168 Sweat gland tumours, 786 Swine flu, 185-86 932 Tophi, 854f INDEX TORCH complex, 190-91 Torsion testis, 706 Torticollis, 521 Toxic granules, in neutrophils, 348 Toxic shock, 109, 110-11 Toxoplasmosis, 191 TP53 gene, 213 Trace elements, 254 Tracheo-oesophageal fistula, 538 Trachoma, 508 Tram-track appearance, 671 Transaminases, 595, 898 Transcellular fluid, 93 Transcobalamin, 253, 303-04 Transcoelomic spread, 202-03, 750 Transferrin, 295 Transfusion, of blood, 339-40 complications of, 339-40 Transient ischaemic attacks (TIA), 879 Transitional cell carcinoma, nasopharynx, 518-19 urinary bladder, 700-02 Translocations, 199, 259, 353, 355, 356f, 358 reciprocal, 259 Robertsonian, 259 Transplant rejection, 65-66 Transplantation, 65 cardiac, 460 bone marrow, 326, 365, 374 Transposition of great arteries, 425-26 Transthyretin, 83 Transudate versus exudate, 96t Trauma to brain, 882-83 Trephine, 286-87 Treponema, 161 Trichoepithelioma, 785 Trichomoniasis, 270f Trigone, 698 Triphenyl tetrazolium chloride (TTC), 432 Triple response, 131f Trisomy, 258 Tropical pulmonary eosinophilia, 456, 494 Troponins, cardiac, 417, 435 Trouisier’s sign, 557 Trousseau’s syndrome, 232, 410, 503, 648 Truncus arteriosus, persistent, 425 Trypanosomiasis, 453, 538, 580 Tryptophan, 243 Tubercle, 152-53, evolution of, 152-53, 155, 156 hard and soft, 153 Tubercle bacillus, 149 Tuberculin test, 152 Tuberculoma, brain, 877 Tuberculosis, 149-57 brain, 877 caseous necrosis in, 45, 153, 155, 156 caseous pneumonia in, 156 causative organism in, 149 cavitary, 155-56 clinical features of, 156-57 dystrophic calcification in, 52f fibrocaseous, 155-56 hypersensitivity and immunity in, 152 incidence of, 151 intestinal, 569-71 kidney, 156, 684 liver, 162, 615-16 lymph node, 45, 154f meninges, 876 miliary, 162 nose, 517 open, 155 oral cavity, 523 primary, 153-55 pulmonary, 154-56 secondary, 155-56 sinus tracts in, 153 spread of, 151-52 transmission of, 151 Tuberculous meningitis, 876 Tubular necrosis, acute (ATN), 679-80 Tubules, diseases of, 678-80 structure of, 651-52 Tubulointerstitial disease, 680-85 Tumoral calcinosis, 779 Tumour host interrelationship, 228-32 Tumour markers, 233-34, 709, 720 Tumour necrosis factor (TNF), 25-26, 109, 138-39, 146, 230, 381 Tumours (also see under Neoplasia), 192-235 anaplasia in, 197 angiogenesis in, 199, 215 benign versus malignant, 194 characteristics of, 194-204 classification of, 193t cytomorphology of, 197-99 diagnosis of, 232-35 differentiation in, 197 epidemiology of, 205-07 etiology and pathogenesis of, 208-28 functional changes in, 198 genetic abnormalities in, 199 grading of, 204 gross features of, 196 growth rate of, 194-96 inflammatory reaction in, 199-200 invasion of, 200-04 metastasis in, 200-04 microscopic features of, 196-200 phenotype of, 196 spread of, 200-04 staging of, 205 stem cells in, 196 stroma of, 199 vascular invasion of, 201-02 Tunicae, arteries, 390 Turban tumour, 786 Turbulence, 116, 133 Turcot’s syndrome, 586 Turk cell, 349 Turner’s syndrome, 258 Typhoid fever, 571-72 Typhoid ulcers, 572f Tyrosinase, 40 U Ubiquitin, 26 UICC staging, 205 Ulcer, amoebic, 187-88 aphthous, 522-23 Curling’s, 113, 550 Cushing’s, 550 peptic, 549-54 rodent, 784-85 stress, 550 Ulcerative colitis, versus Crohn’s disease, 566t Ultimate carcinogens, 218 Ultraviolet light, 34, 221 Unicameral, bone cyst, 839-40 Union, wounds, 168-69 primary, 168 secondary, 168-69 Urachal abnormalities, 698 Urachal cyst, 698 Uraemia, 655-56 Uraemic manifestations, 655-56 Urate nephrolithiasis, 692 Ureter, normal structure of, 698 Ureterocele, 698 Urethra, normal structure of, 698 Urethral carcinoma, 702 Urethral caruncle, 702 Urethritis, 699-700 Uric acid stones, 692 Urinary bladder, 698-700 normal structure of, 698 tumours of, 700-702 Urinary calculi, 690-92 Urinary cytology, 273, 276 Urinary tract infection (UTI), 681, 682, 698 Urinary tract, lower, 698-702 Urine analysis, 652 Urobilinogen, 593 Urolithiasis, 690-92 Uropathy, obstructive, 690-93 Urothelial tumours, 700-02 Urticaria, 97, 770 Urticaria pigmentosa, 770 Uveal melanoma, 512 Uveitis, 508 V Vaccines, hepatitis, 614 Vaccinia, 186, 773 Vagina, 723-24 normal structure of, 723 tumours of, 723-24 Vaginal smear, 268-72, 275 Vaginitis, 723 monilial, 270, 723 Valvular deformities, 426, 449-51 Valvulitis, rheumatic, 440-41 van den Bergh diazo reaction, 593 Vanillyl mandellic acid (VMA), 800 Varicella-zoster infection, 186, 773 Varices, 539-40, 631-32 Varicocele, 706 Varicosities, 409 Variola, 186, 773 Vasa recta, 650 Vasa vasora, 390 Vascular purpuras, 331 Vascular permeability, 130-33 alterations of, 131 mechanisms of, 131-33 Vascular tumours, 411-16 Vasculitis, 400-05 allergic, 402-03 hypersensitvity, 402-03, 404 leucocytoclastic, 403f lymphocytic, 403 Vasoactive amines, 136-37 ... specific segments of the heart (Fig 16 .2) : Systemic Pathology The anterior descending branch of the left coronary artery supplies most of the apex of the heart, the anterior surface of the left ventricle,... occurs in the form of proliferation of smooth muscle cells with fibrosis Necrotising Arteriolitis Systemic Pathology In cases of severe hypertension and malignant hypertension, parts of small arteries... as under (Table 15 .2) : i) Total cholesterol: Desirable normal serum level is 140 -20 0 mg/dl, while levels of borderline high are considered between 20 0 -24 0 mg/dl An elevation of total serum cholesterol