Medical morbid anatomy and pathology

Preface

Our object has been to provide students with a concise account of the morbid anatomy of medical diseases and enough pathology to explain the lesions described.

For the convenience of members of our own school we have given marginal references to specimens in the Museum of St. Bartholomew’s Hospital which illustrate the statements made in the text, and recommend that these specimens be studied with the aid of the descriptive catalogues to be found in that Museum.

We have written from our own experience when this has been adequate, but are much in debt to many friends and authors of text-books. These obligations we acknowledge gratefully, and hope that the result may be found of practical value.

H. T.

Contents

CHAPTKR

I. Introductory

II. Diseases of Bone

I. Inflammation

“ Inflammation is the reaction of irritated and damaged tissues which still retain their vitality.” This is the definition offered by Grawitz, and it is the most acceptable one. In medical pathology the irritant causing inflammation is generally bacterial ; but it may be derived from ingested poisons or poisons elaborated by abnormal metabolic processes, or result from the defective excretion of normal metabolic products.

The purpose served by inflammation is the repair of damage, including under this head the neutralisation of poisons, chemical or bacterial : the removal of irritant substances (whether simple foreign bodies such as a piece of an aseptic ligature, or the dead products of the damage causing the reaction, or bacteria) : and finally, the regeneration of tissue to replace that which has been destroyed.

The most prominent immediate results of inflammation are : (1) An accumulation of cells. (2) An effusion of fluid, in and around the damaged area. It is proposed in the following pages briefly to describe : I. The mechanisms by which these aims are achieved. II. The characters of, and the parts played by, the cells and fluids thus accumulated. III. The sequelae of inflammation.

I. The mechanisms by which cells and fluid are accumulated

in inflamed areas.

(a) The Cells.

1. Chemiotaxis. — There exists between certain living cells and various chemical substances, including dead tissues and foreign bodies such as bacteria, a relation evinced either by an attraction or a repulsion exerted by the chemical substance upon the cells. This relation is called “ Chemiotaxis.” When attractive, the relation is called “ positive,” when repellent, “negative” chemiotaxis. The phenomenon is well illustrated by the behaviour of a myxomycetes (which may be described as a multi-nucleated amoeba) found in tan pits. If such an organism be placed upon a moistened surface near a drop of an infusion of oak-bark, it moves actively towards and into the infusion. This is positive chemiotaxis. If, on the other hand, the infusion be replaced by a 0 5 per cent, solution of glucose, the organism moves with equal rapidity away from it. This is negative chemiotaxis.

A little higher in the scale of living things the bearing of chemiotaxis upon inflammation becomes pronounced. At one stage in development the larval forms of certain metazoa consist of an ectoderm, invaginated at one point to form the endoderm, while between the two lies the mesoderm, a semi-liquid mass containing amoeboid cells. This is the body-cavity of the larva. In such an organism the phenomena of inflam mation are simplified by the absence of blood-vessels, and are limited to cell-accumulation. If a foreign body lie thrust into the larva it becomes surrounded by wandering mesodermal cells attracted to it by positive chemiotaxis.

In vertebrates there exists a noil-vascular tissue analogous to the body-cavity of the larval metazoon above described, the cornea, which in health contains no blood-vessels, but an ample supply of lymph-channels. If the cornea of a rabbit be cauterised, or if a piece of it be removed, a whitish opacity appears in the immediate neighbourhood of the injury. This opacity is due to an accumulation of small round cells, and appears without any evidence of vascular dilatation around the cornea or of proliferation of the corneal corpuscles. The cells are wandering leucocytes attracted from the surrounding lymph-spaces by positive chemiotaxis.

When a more intense inflammation is excited, as for example by the injection of a pus-forming organism like the staphylococcus pyogenes aureus, there appears within twenty-four hours a dense packing of leucocytes around the damaged zone. But the accumulation is now attended by obvious changes in the veins at the periphery of the cornea. They are dilated, and it is apparent that leucocytes are passing from the bloodchannels into the lymphatic spaces. This passage of leucocytes will be presently described in detail. It is enough, at present, to note that it is largely the result of positive cbemiotaxis.

Under certain conditions the attraction of leucocytes fails to manifest itself, or may be exchanged for an active repulsion. Both these events are embraced by the term “negative chemiotaxis.” Negative chemiotaxis attends irritants whose characters place them at one or other extreme in the scale of virulence, and results in an inflammatory exudate consisting chiefly of fluid. Thus infections due to bacteria of relatively low virulence, like the tubercle bacillus, or to bacteria of a high degree of virulence, such as those responsible for somo forms of acute purulent peritonitis, are alike marked by an exudate composed largely of fluid and to a small degree only of cells, though the character of the fluid varies in the two cases.

2. Vascular changes attending inflammation. -It has been noted that some of the leucocytes accumulated in areas of inflammation are wandering cells from neighbouring lymphatic spaces. A second contingent, haomatogenous leucoc}rtes, is > derived from the blood as a result of the following vascular * changes. By these changes leucocytes are massed upon the outskirts of the scene of operations, whence they are drafted into the fighting line under the influence of chemiotaxis.

The first effect of an injury or irritation, as regards the blood-vessels of the injured part, is dilatation of the arterioles, venules and capillaries in succession, associated with an increase in the rate of the blood-flow through them. The corpuscles travel in the centre, or “axial” stream, while at the periphery is a zone of cell-less plasma. Presently the pace of the blood-current abates, and the axial stream of corpuscles widens out. At its edge, now situated close to the wall of the vessel, leucocytes are seen, travelling more slowly than the axial current, adhering momentarily to the wall, and then advancing in a series of jerks as though they, or the wall, had become sticky. Finally the vessel becomes completely blocked with cells, and the blood-flow through it ceases. This is the stage of Stasis. With the gradual stoppage of the current the Diapedesis or migration of leucocytes commences, and is attended by an escape of fluid from the distended vessels. The leucocytes aggregated within the venules and capillaries penetrate the delicate walls of these channels by the exercise of amoeboid movements, and are shortly to be seen in large numbers in the lymph-spaces outside the vessels from wrhich they are derived, actively making their way to the site of damage under the influence of chemiotaxis. This leucocytic migration is attended in its later stages by the escape of red-corpuscles in varying abundance. It is generally accepted that the escape of red-cells is a passive process, a means of exit being found, in part at least, in the orifices made by the migrating leucocytes.

3. Changes in the fixed connective-tissue cells. — There is a third important source of supply of leucocytes, namely the fixed connective-tissue cells of the injured area, especially the endothelial cells lining capillaries and lymph-spaces. It is characteristic of endothelial cells that under the influence of irritants they cease to be flat, and, becoming swollen, proliferate actively, giving rise to large hyaline leucocytes. This phenomenon has been studied most extensively in relation with the endothelial lining of the peritoneum, but is general. Further, connective-tissue corpuscles themselves, and even highly-specialised cells like muscle-fibres, are capable of a similar proliferation.

To sum up, the cells of the leucocytic accumulation comprise: (1) Wandering cells from the lymphatic spaces. (2) Haemal leucocytes, released from the blood by the series of changes which lead to diapedesis. (3) Leucocytes supplied by the proliferation of fixed connective tissue cells, particularly of the endothelial cells lining lymph-spaces and capillaries.

(b) The Fluid of the Inflammatory Exudate.

Little is known of the mechanism which produces the fluid exudations of inflammation, but whenever injury or irritation leads to vascular dilatation an increased escape of fluid from the blood is a feature of the process. The characters of, and the services rendered by, the fluid exudate will be presently considered.

II. The characters of, and the parts played by, the cells and fluid of the exudate.

(a) The Cells of the Exudate.

We have seen that the leucocytes of inflammation own a variety of origins. They have also a variety of duties, though our knowledge on this point is incomplete.

The prime functions of the leucocytes, apart from their relations to immunity which are here omitted from consideration, appear to be the following: (1) To remove particulate irritants such as bacteria and dead tissues, and to counteract the poisons locally at work. (2) To regenerate destroyed tissues. The former of these functions is accomplished partly by the ingestion, and subsequent intra-cellular digestion, of the offending particles by certain types of leucocyte ; 1 partly by the extra-cellular action of ferments either excreted by the leucocytes, or liberated from them upon their death in the inflamed zone. The leucocytes which evince the capacity for ingesting particulate bodies are called Phagocytes.

Of the leucocytes concerned with inflammation some are essentially blood-leucocytes (llacmatogenous). They originate in the bone-marrow and thence enter the blood-stream, reaching the inflamed zone by diapedesis. Such are polymorpho nuclear, eosinophil, and mast cells. Others arc directly derived from tissue-cells (Histogenous). They originate in proliferated endothelial cells, connective-tissue corpuscles, or lymphoid tissues, and arrive direct upon the scene of action without passing through the blood-vessels. Such are a certain propor-

1 Particles which resist digestion, such as granules of carbon, and occasionally living bacteria, may bo ingested, carried to the lymphglands and there deposited.

tion both of large hyaline leucocytes, and of lymphocytes. A third group is formed by the remaining fraction of these two last types. Though essentially histogenous they enter the blood-stream and reach the area of inflammation by the same route as the haematogenous forms. This group is therefore termed Histo-haematogenous.

1. Polymorphonuclear cells. — These are the most abundant leucocytes in foci of acute inflammation. They are actively phagocytic, especially as regards bacteria, and are the typical pus-cells. In addition they either excrete, or liberate upon their death, antidotes to bacterial poisons, and substances assisting in the digestion and solution of bacteria and dead tissues. They may die and be dissolved in situ, or may be ingested by large hyaline leucocytes. They play no part in tissue-regeneration.

2. Eosinophil cells. — These are seldom numerous, and are practically not phagocytic. It is presumed that they excrete some substance conducive to repair, but nothing definite is known of it. They play no part in tissue-regeneration.

3. Mast-cells (coarsely-granular basophil cells). — These are not abundant, and of their functions nothing is known.

4. Large hyaline cells. — These are not so common as the polymorphonuclears. They are phagocytic, and readily ingest other cells and cell-ddbris, but attack bacteria less actively than do the polymorphonuclears. In areas of chronic inflammation they may form giant-cells, either as a result of fusion of several individuals, or of nuclear multiplication in a single one. They arc actively concerned in the regeneration of tissue.

5. Small hyaline cells (Lymphocytes). — These are the preponderating cells in areas of chronic inflammation, and form the “small round cell” infiltration found in such lesions. They are not phagocytic. It is a matter of doubt whether or not lymphocytes take part in tissue regeneration, but there is evidence that they may be transformed into “ plasma-cells.”

6. Plasma cells are uni-nuclear cells. The nucleus is small (relatively to the cell-body), oval or round; excentrically situated, and stains deeply. Plasma-cells are common in all areas of chronic inflammation, especially those due to the virus of syphilis. Their role and their fate are both uncertain.

(l>) The Fluid Exudate.

The fluid exudate of inflammation differs from ordinary lymph in being richer in proteids, approximating in this respect to blood-plasma. This protoid richness is in part attributable to the leucocytes and tissue-cells which become disintegrated within the exudate, in part to an increased transudation from the distended capillaries of the area concerned. In addition the fluid exudate contains digestive ferments and bactericidal substances. It is usually rich in fibrin-forming elements (except in the case of very virulent bacterial infections), and tends to coagulate, especially upon serous and mucous surfaces, but also within the tissues. Some varieties of bacterial infection excite fibrin-formation to a much more pronounced degree than others, the diphtheria bacillus and the pneumococcus being especially gifted in this respect.

The functions of the fluid exudate are (with others, which are in dispute) the following :

1. It flushes the injured area and dilutes the irritant.

2. The development of fibrin within it tends to limit the spread of inflammation.

3. It exercises a digestive function, by virtue of the cells disintegrated within it, and thus aids in the removal of dead products of irritation.

4. It probably contains substances, similarly derived from cells, capable of hindering the growth of bacteria.

III. Sequelae of Inflammation.

1. Resolution.

2. Suppuration.

3. Gangrene.

4. Fibrosis.

1. Resolution. — The term “ Resolution ” has no strict pathological significance, but is commonly and conveniently used to describe a rapidly-established ascendancy of the defensive over the destructive forces at work. Both the irritant and the dead products of its activity are rapidly removed : there is at no time a gross accumulation of necrotic material ; and the inflamed part is restored to health with a minimum of structural alteration.

2. Suppuration. — When the irritant is virulent the destruction of leucocytes and tissue-cells outstrips, for the time at least, the reparative capacity of the organism. In consequence the destroyed leucocytes lie where they fall, suspended in a fluid exudate. Such an exudate containing dead leucocytes is called pus. Pus may be a thick and creamy, or a thin and turbid fluid, and in the latter case is often blood-stained. Thick pus, the “laudable pus” of old writers, indicates an irritant of moderate severity. The abundance of cells in it is evidence of active positive chemiotaxis. Thin turbid pus is evidence of negative chemiotaxis, and thus of a virulent irritant. When pus is formed one of two events occurs. In the one case, although the day goes against the leucocytes at the spot where the irritant is most active, the surrounding zones fare better. Here, remoter from the poison, leucocytic accumulation and fibrin-formation produce a barrier 1 by which the inflammatory agent is confined, and the result is a localised collection of pus — an abscess. In the other case the virulence of the irritant is such that no marked accumulation of leucocytes occurs : positive chemiotaxis is in abeyance, and no barrier is formed, and thus a large area of tissue may become the seat of a diffuse suppuration. (Phlegmonous inflammation.)

The fate of an abscess. — (1) “Pointing” and discharge. (2) Inspissation and encapsulation.

(1) “ Pointing.” — Collections of pus acutely formed are commonly under pressure, and thus tend to advance in the direction of least resistance until they reach a surface. Here, under the combined influence of pressure and of the softening influence of the inflammation they excite in their immediate neighbourhood, they “point,” perforate the surface, and discharge their contents.

(2) Inspissation and encapsulation. — Chronic abscesses, resulting from irritants of relatively low virulence, show less inclination to extend. Their fluid constituents tend to be absorbed in course of time, leaving a pultaceous mass of cell debris, prone to infiltration by lime-salts. In this way

1 The barrier of leucocytes and fibrin which forms the immediate wall of an abscess is called “granulation-tissue” ( v . p. 9).

SEQUELAE OF INFLAMMATION the inspissated material may be converted into a chalky plate or stone. Coincidently the chronic irritation of the mass produces tissue-regeneration about itself, as will presently be described, with the result that eventually the remains of the abscess are enclosed in a firm fibrous capsule.

3. GangTene implies a widespread and rapid death of tissue in bulk. It may result from other causes than inflammation, for instance obstruction to blood-supply, but with such examples we are not here concerned. Inflammatory gangrene is the consequence of a wide spread onslaught of virulent bacteria leading to the rapid death of large areas of tissue. In respect of medical pathology inflammatory gangrene most often affects the lung.

4. Fibrosis. — The extent of tissue-regeneration is proportionate rather to the duration than the severity of inflammation. Acute inflammations cause little of it, chronic inflammations much. Further, whereas no tissue is immune to inflammation, the regeneration of tissues lost as a result of inflammation is, in man, almost confined to the production of one type only, namely fibrous tissue. Thus highly specialised structures, nervous tissue, muscle, etc., when destroyed by inflammation, are in the main replaced by fibrous tissue. This replacement is termed Fibrosis, and is a fruitful source of ulterior disease owing to the inevitable tendency of inflammatory fibrous tissue to contract with time. Whether upon the skin, or within the lung, liver, kidney, or elsewhere, newly-formed fibrous tissue gradually cicatrises, deforming the organ affected and crippling its functional activity.

Source of the new tissue. — If the surface layers of the wall of an abscess be examined microscopically they arc found to consist of delicate strands of fibrin, enclosing in their meshes leucocytes of various kinds. Somewhat deeper the stroma assumes a greater density, its fibrils are thicker and are interspersed with spindle-shaped cells and fine capillary bloodvessels. Such material is called “granulation tissue.” The spindle- -shaped cells are fibroblasts, derived from the histo genous leucocytes and from pre-existing connective-tissue cells at the margin of the inflamed area. They are presently converted into definite connective tissue corpuscles, their protoplasm becoming modified into parallel fibrils of young fibrous tissue, while their nuclei undergo a gradual shrinkage.

I lie capillary loops seen in granulation tissue are believed to be derived from buds, given off from pre-existing capillary loops at the periphery of the area, and subsequently channelled.

CLINICAL VARIETIES OF INFLAMMATION NOT YET ENUMERATED.

1. Catarrhal inflammation. — This term is applied to inflammations of surfaces covered by mucous membrane. It is attended by swelling of the membrane and by an exaggeration of the normal secretion of mucus. When severe, catarrhal inflammation commonly leads to ulceration.

2. Membranous or croupous inflammation. — This signifies an inflammation of a surface, either mucous or cutaneous, attended by an abundant deposit of fibrin, which forms a membranous pellicle upon the affected part. The type of this variety is diphtheritic inflammation, though other organisms besides the diphtheria bacillus are capable of causing it.

3. Serous inflammation. — This implies an inflammation characterised by an abundant coagulable fluid exudate. Its simplest type is the inflammation produced by a blistering fluid ; but certain bacteria of a low degree of virulence afford examples of it. This is particularly the case with the tubercle bacillus acting upon a serous membrane like the pleura. The term “serous inflammation” has a purely clinical significance.

4. Ulceration. — An ulcer is a surface which has lost its natural covering of mucous membrane, endothelium, or skin, either as a result of inflammation or of infiltration by malignant tumours. Inflammatory ulcers are produced by a chain of events analogous to those which produce an abscess, but the affected site being superficial, the dead products are removed as rapidly as they are formed, and do not accumulate. The floor of an inflammatory ulcer, like the wall of an abscess, is composed of granulation-tissue.

RETROGRESSIVE TISSUE CHANGES.

The terminology of retrogressive changes is very confused, because the stages and manifestations of impaired vitality lying between health and death pass one into another by imperceptible gradations and often coexist in the same example. It is possible to define more or less exactly the following four groups, with the qualification that in practice no one of them is likely to occur alone :

1. Atrophy.

'1. Necrosis.

4. Infiltrations.

1. Atrophy indicates wasting of a tissue without any qualitative alteration in its constituent elements. Nevertheless it is a rule of pathology that highly -specialised structures such as nervous tissue, glands and muscles, are less resistant to an injurious environment than those less specialised, such as fibrous tissue : and in consequence the highly-specialised elements in an atrophic tissue suffer first, and most profoundly. Atrophy is usually associated with fatty degeneration.

Causes of atrophy. — The nutrition of a tissue depends very largely upon its functional activity, and thus the commonest cause of atrophy, in the sense defined, is disuse. Many atrophies are physiological, for example those affecting the ductus arteriosus and the ductus venosus at birth : the wasting of the thymus gland after the first two years of life, and the involution of the uterus after parturition. The commonest example of pathological atrophy is the wasting of muscles observed about a joint rendered immobile by disease.

2. Necrosis means tissue-death. Its causes are (a) Mechanical injury, (b) The action of poisons, whether chemical or bacterial. (c) Sudden arrest of nutrition, brought about generally by obstruction of the blood-supply (as is the case with infarction of the viscera and gangrene of the extremities), but sometimes by a failure in the nutritive function of the nervous system (as is the case with some acute forms of bed-sore).

Cell-death is evidenced by changes both in the nucleus and cell-body. The nucleus ceases to retain ordinary nuclear dyes, while the cell-body becomes distended by coagulated lymph, whence the term “coagulation-necrosis.” It is believed that the death of the cell permits the entrance of lymph, the latter being coagulated in situ by a substance liberated upon the death of the nucleus. An area of coagulation-necrosis may become liquefied by the ferment action of bacteria. On the other hand it may be liquefied almost from the beginning, as is the case with necrotic areas in the brain : for here the intercellular lymph (cerebrospinal fluid) is not coagulable. In either case the result is described as “ colliquative necrosis.” The necrosis of tissues en masse (excepting the extensive necrosis of bone which results from inflammatory detachment of periosteum) is called Gangrene. Arrest of the blood-supply to an extremity, in the absence of putrefactive organisms, pi’oduces a gradual blackening and mummification of the starved area. (Dry Gangrene.) In soft tissues such as the lung, and in the extremities when putrefactive organisms have gained access to the dead tissue, Gangrene is “ Moist.”

The fate of necrotic tissues has been in part described in the section upon inflammation, where the extra-cellular digestion of them, their removal by phagocytosis, or by the pointing and discharge of abscesses, and their encapsulation by fibrous-tissue, have been briefly recounted. It remains to mention Caseation, a common termination of coagulation-necrosis. Caseation means the conversion of the necrotic material into a white or yellowish substance having the appearance and consistency of cheese. Caseation is a particular feature of necrosis produced by the tubercle bacillus, and by the virus of syphilis. As will be seen below, caseous accumulations are very prone to infiltration by lime-salts.

3. Degenerations. — Prolonged exposure of a cell to deleterious influences such as insufficient nourishment, or to a nutritive fluid containing poisonous elements, causes alterations in the constitution of the cell. The cell is sick and may die, but it dies slowly, undergoing in the meanwhile a gradual conversion into compounds foreign, whether as to quantity, or quality, or both — to its constitution in health. This retrogressive metamorphosis of the cell-tissue itself is the commonly-accepted criterion of “degeneration” in the narrow sense which opposes it to “ necrosis ” on the one hand and to “infiltration” on the other; infiltration implying the deposit • within a cell of some substance brought from without. The i distinction is worth observing for purposes of description, but it cannot always be maintained, especially in the case of fatty i changes.

Degenerations. — (a) Cloudy swelling; (b) Fatty degeneration; (e) Albuminoid degeneration.

(a) Cloudy swelling. — The organs of those who die rapidly after poisoning by antimony, phosphorus, and certain other poisons, or more slowly, after febrile diseases like typhoid fever or scarlet fever, commonly exhibit a generalised swelling and lack of lustre. Microscopic examination shows that the cells of the affected tissue are enlarged : their outline is obscured, and their protoplasm occupied by granules proved to be of an albuminous nature. This change is called “Cloudy swelling.” It is most marked in the liver, kidneys, heart and voluntary muscles, and is often the first step towards fatty degeneration, notably when due to phosphoruspoisoning.

(b) Fatty degeneration. — Fatty degeneration was held by Virchow to be the result of conversion of cell-proteids into fat. It is now believed by many that the intra-cellular globules of fat, which are accepted as microscopic evidence of fatty degeneration, are due to the fusion, into visible droplets, of the fat which is a normal, though not visible, constituent of a healthy cell. The point is somewhat academic. It is sufficient for our purposes to observe that the appearance of fat globules within cells which do not normally contain visible fat is evidence of fatty degeneration

Fatty degeneration may be a physiological process, as it is in the case of the lactating breast. For the fat of milk is supplied by degeneration of the central cells of the mammary acinus. On the other hand fatty degeneration plays an immense part in pathological processes. It occurs at some stage in nearly all lesions of any duration, and to some extent in acute inflammations. It is seen in the dead leucocytes of pus, and in the viscera of those who have died from wastingdiseases like diabetes mellitus, pulmonary tuberculosis and cancer. It attends continued suppuration, chronic heart-disease, severe anaemias, and many kinds of poisoning. Indeed, there is hardly a chronic disease which proves fatal without entailing fatty degeneration in some organ.

Fatty degeneration gives to the tissue affected a yellowish pallor. In an advanced case an oily exudation may appear upon section.

Microscopic examination shows that the cells of the tissue arc enlarged and their nuclei displaced by globules of fat. These globules are stained black by Osniic acid and yellow by Sudan III.

(c) Albuminoid degenerations. -(1) Mucoid degeneration; (2) Hyaline degeneration ; (3) Colloid degeneration ; (4) Amyloid degeneration.

In a variety of diseased conditions cell-protoplasm undergoes conversion into a homogeneous albuminoid material. The terminology of these degenerations is vague and confused, partly because the chemical constitution of the new bodies is varied in different cases and situations, partly because the descriptive terms in use denote characteristics which are sometimes chemical ( e.g . “ mucoid ” and “ amyloid ”), sometimes physical (e.g. “hyaline” and “colloid”).

(1) Mucoid degeneration. — Mucin is a compound proteid containing a carbo-hydrate element, and thus when boiled with an acid produces a substance capable of reducing Folding's solution. It is precipitated by acetic acid and has an affinity for basic dyes. But there are a number of allied substances, pseudo mucins, which are not precipitated by acetic acid and have an affinity for acid dyes. Degenerations resulting in the production of mucinous material in either of these forms are called mucoid degenerations. They fall into two groups, according as the structures attacked are epithelia or connective-tissues.

(a) Epithelial mucoid degeneration occurs particularly in tumours of parts which normally produce mucin, such as cancers of the stomach and intestine, but is met with also in the breast and elsewhere. The degeneration is often widespread, and then converts the tumour into a semi transparent mass. Under the microscope the affected tissue appears structureless and homogeneous. Cells are scanty, or absent altogether. Such as survive have a bloated appearance owing to their distension by mucoid material. It is customary to speak of cancers which have undergone this degeneration as colloid cancers,” a fact which emphasises the laxity of phrase current in this connection.

(b) Connective tissue mucoid degeneration affects a great variety of connective-tissue tumours, fibromata, lipomata, i shondromata, and sarcomata. The degeneration may be so ■ extensive that no trace of the original structure persists (Myxoma). In certain tumours, especially those of the ovary, mucoid degeneration leads to the formation of cysts.

(2) Hyaline degeneration. — There is no one substance to which the term “hyalin” can be applied. “Hyaline degeneration” means the conversion of tissues into a pathological,

1 homogeneous, clear substance with an affinity for acid dyes I like eosin and fuchsin. This substance may appear in epithelial cells (epithelial hyalin) or in connective-tissues, (connective-tissue hyalin). Hyaline casts of renal tubules are a good example of epithelial hyalin. The conversion of connective-tissues into hyalin occurs in old scars, in the degenerate glomeruli of chronic interstitial nephritis, and in the walls of arteries. “Zenker’s hyaline degeneration of muscle fibres ” is an analogous lesion common after death from typhoid fever.

(3) Colloid degeneration. — Properly speaking “Colloid de- -generation ” means the conversion of tissues into a substance resembling the normal iodine-containing secretion of the thyroid gland. In this limited sense colloid degeneration is rare except in tumours of the thyroid and, perhaps, ipituitary glands. But in the commoner vague acceptation it embraces mucoid degeneration.

(4) Amyloid degeneration (lardaccous or waxy degeneration). — This is a well-differentiated form, characterised by the appearance in the tissues of a colourless, semi-transparent substance. This “amyloid material,” when treated with a watery solution of iodine containing iodide of potash, becomes of a mahogany-red colour, changing as a rule, but not always, to blue upon the addition of sulphuric acid. Amyloid material is believed to be due to the interaction of damaged cellsubstance and chemically-altered lymph.