Contributions to physiology & pathology

Front matter

22101856826

Med

CONTRIBUTIONS

Introduction

The morbid process designated by the term Inflammation, being one to which every organ and probably every tissue of the body is liable, and comprehending as it does in its progress and consequences by far the greater number of the ills to which flesh is heir, possesses a deeper interest for the physician or surgeon than any other material subject which could be named. The practical importance of inquiries tending to elucidate the essential nature of this process, has been for centuries recognized by all enlightened members of the medical profession ; for it is obvious that just views regarding it must tend to promote the establishment of sound principles in the treatment of the diseases which it produces. At the present day more especially, when theory is allowed such free scope, and is permitted to attack the most time-honoured rules of practice, we stand in peculiar need of the beacon-light of correct pathology to enable us to steer a safe course amid the various conflicting opinions which assail us. Yet so far from our knowledge of inflammation being in a satisfactory condition, authorities are at variance upon the fundamental question, whether it is to be regarded, in accordance with John Hunter’s opinion, as active in its nature, and consisting in an exaltation of the functions of the affected part, or whether it should not rather be considered a passive result of diminished functional activity.

In seeking for the solution of this great problem, we cannot expect to gain much from the contemplation of the more advanced stages and results of inflammation, such as copious exudation of lymph, suppuration, ulceration, or gangrene. When any one of these has taken place, the nature of the original disease is masked to a great extent by the subsequent changes; and the cell-development which occurs in lymph after its effusion, is no more proof of activity in the inflammatory process, than the loss of the vital powers in gangrene can be accepted as evidence in the opposite direction. It is upon the first deviations from health that the essential character of the morbid state will be most unequivocally stamped, and it is therefore to the early stages of inflammation that attention must be chiefly directed in this inquiry.

If the palm of the hand be chafed by long-continued friction, as for example in rowing a boat, the first thing that will be observed, when attention has been directed to the pait by a feeling of uneasiness, will be that the skin is redder than natural, implying

MR. J. LISTER ON THE EARLY STAGES OF INFLAMMATION.

that the vessels are abnormally loaded with blood, and if the irritation be continued, the cuticle will be raised in the form of a blister. If, now, the loosened epidermis be artificially removed on the earliest occurrence of effusion, a scarlet raw surface will be exposed ; and on pressing the tender dermis firmly with the finger, and suddenly removing the pressure, it will be found that while the redness will for the most part have momentarily disappeared, there will be many minute red points from which the blood cannot be expelled. This shows that, while the blood is in part still free to move, there are some minute vessels completely clogged with it. Again, if a portion of mustard be placed on the skin covering the dorsal aspect of one of the fingers, abnormal redness will very speedily be produced, which in the first instance disappears completely on pressure ; but, if the mustard has been kept on long enough, can be only imperfectly dispelled; and if the application be still longer continued, vesication will be the result. I had lately the opportunity of examining the brain of a man who had died of tetanus, complicated with incipient meningitis ; the post mortem appearance of the latter being maculiform congestion of the pia mater. Having stripped off a portion of the affected membrane, and carefully washed away with a camel’ s-hair brush the cerebral substance adhering to it, I applied the microscope to one of the affected spots, and found that all the minute vessels were filled with crimson blood, while those of the surrounding parts were comparatively pale. It was evident that the red corpuscles were, in the former, so closely crammed together as to produce the appearance of a uniform mass, while in the latter they were present only in their usual proportion to the liquor sanguinis. Thus it appears that in the human subject, inflammation, whether induced by mechanical irritation or by an acrid application such as mustard, or of spontaneous origin, is characterized at an early period by a certain amount of obstruction to the progress of the blood through the minute vessels; a phenomenon, which it is therefore of great importance to understand.

It fortunately happens, that we have, in the transparent web of the frog’s foot, an opportunity of observing with the utmost facility the circulation of the blood in the living animal, and of watching the effects produced upon it by irritating causes. It may naturally appear very doubtful whether observations made upon creatures so low in the animal kingdom as the Amphibia, can with propriety be brought to bear upon human pathology. A few facts will, however, suffice to show that no such doubts need be entertained. If a portion of moistened mustard be placed upon the web of a frog, tied out under the microscope, the blood-vessels will soon be found abnormally red ; and if the application be continued long enough, all the capillaries will become choked with corpuscles so closely packed as to present the appearance of a uniform crimson mass ; and by and by the epidermis will be found raised in the form of a blister over the part on which the mustard lay. These effects are precisely similar to those which we have seen to be produced by it upon the human skin; and before effusion has taken place, the vessels of the affected part exactly resemble those of the congested spot of inflamed pia mater above described. Again, if dry heat be made to act upon a part of the frog s foot,

MR. J. LISTER ON THE EARLY STAGES OF INFLAMMATION.

there will result, in proportion to the elevation of the temperature and the duration of its action, undue redness of the vessels from accumulation of the blood-corpuscles ; and if the burn have been sufficiently severe, vesication will soon take place as in the human subject. These and other similar cases indicate that the early stages of inflammation are alike in man and in the frog, and this conclusion is fully confirmed by examination of the bat’s wing, which furnishes the means of watching the effects of irritants upon mammalian circulation. The very small size of the blood-corpuscles, and some other circumstances, render that animal much less suitable for the investigation than the frog ; but with the use of high powers of the microscope and a little pains, the same sort of experiments can be made with both : and the careful observations of Messrs. Paget and Wharton Jones, and, I may add, also my own more limited experience witli the bat, have shown that in all the details that can be observed, a complete similarity obtains between the effects of irritation upon the circulation in the two creatures. We may therefore rest fully satisfied that conclusions arrived at from the study of the early stages of inflammation in the foot of the frog will apply in all strictness to the same morbid process in man.

It is well known that the field of observation thus afforded has not been allowed to remain uncultivated. Since the microscope has been brought to its present state of perfection, not to speak of a previous period, men of established scientific reputation have devoted much patient labour to it ; and any one who now enters upon this inquiry has the great advantage of possessing faithful records of accurate observations made by many able predecessors. But the number and discordance of the views entertained by different authorities regarding the cause of the “stasis” of the blood in inflammation, are sufficient evidence either that the subject demands further investigation, or else that it lies beyond the reach of human means of research.

Having been called upon in the capacity of a teacher of surgery to attempt an explanation of the matter to others, I felt bound to do my best, by personal observation, to form a judgement for myself; and several new facts which I have unexpectedly met with appear to throw such fresh and clear light upon the nature of disease, that I venture to submit them to the Royal Society.

Section I

On the Aggregation of the Corpuscles of the Blood.

The tendency of the corpuscles of the blood to aggregate together, constitutes, as we shall see, an important element in the cause of the obstruction which they experience in the vessels of an inflamed part. It is therefore desirable that we should be acquainted with the nature of the phenomenon.

If a drop of human blood just shed is placed between two plates of glass and examined with the microscope, the red corpuscles are seen to become applied to one another by their flat surfaces, so as to form long cylindrical masses like piles of money, as first observed in 1827 by my father and Dr. Hodgkin ; and the terminal corpuscles of MDCCCLVIII. 4 Q

ME. J. LISTEB ON THE EARLY STAGES OE INFLAMMATION.

each “rouleau” adhering to other rouleaux, a network is produced with intervals of colourless liquor sanguinis. Rapid movement of the blood prevents this occurrence, but it commences as soon as the corpuscles approach to a state of quiescence, and I have seen short rouleaux already present in a drop drawn from my own finger within ten seconds of its emission. In this respect the aggregation of the red corpuscles differs from the coagulation of the fibrine, which does not begin till some minutes after withdrawal from the vessels. There is, in fact, no connexion whatever between the two processes, as is clear from the circumstance that if a drop of blood is stirred with a needle while coagulation is talcing place, so as to remove the whole of the fibrine, the corpuscles, which have been separated from one another by the agitation to which they have been subjected, aggregate again in the serum in the same manner as they did at first in the liquor sanguinis. The beautifully regular form of the long masses of corpuscles has suggested to some persons the idea of the operation of some peculiar vital attraction in then- formation, while by others the aggregation has been supposed due to merely physical causes, but has never, I think, received a complete explanation. For my own part, I am satisfied that the rouleaux are simply the result of the biconcave form of the red discs, together with a certain, though not very great degree of adhesiveness, which retains them pretty firmly attached together when in the position most favourable for its operation, namely, when the margins of then concave surfaces are applied accurately together, but allows them to slip upon one another when in any other position. There is never to be seen anything indicating the existence of an attractive force drawing the corpuscles towards each other : they merely stick together when brought into contact by accidental causes. Their adhesiveness does not affect themselves alone, but other substances also, as may be seen when blood is hi motion in an extremely thin film between two plates of glass, when they may be observed sticking for a longer or shorter time to one of the surfaces of the glass, each one dragging behind it a short tail-like process ; and as the movement of the blood diminishes so as to permit the formation of rouleaux, the latter may be not unfrequently seen adhering in the same way by one of then terminal corpuscles, as represented in the accompanying diagram.

That the cylindrical character of the aggregated masses is an accidental result of the shape of the blood-discs, is evident from the fact, that in the frog, although the same tendency to agglutination of the corpuscles exists as in Mammalia, yet, as then biconvex form renders it mechanically impossible for them to be applied to one another throughout then entire circumference, they become arranged in groups of an irregular form, as is shown in the annexed sketch of blood contained in a small vein of the frog’s web.

Again, different specimens of mammalian blood differ very much in the amount of adhesiveness of their corpuscles ; and when this property exists beyond a certain degree.

MR. J. LISTER ON THE EARLY STAGES OF INFLAMMATION.

the discs stick together by any parts that happen to come first in contact, and retain that position more or less, so that the result is the formation, not of rouleaux, hut of irregular confused masses. The most striking example which I have seen of this was presented by the blood of a bat, which had lived some days after having been severely wounded. In that case, chains of red discs might be seen adhering firmly by their edges, notwithstanding considerable force of traction operating upon them, and before they at last gave way, tail-like processes of considerable length were drawn out between every pah- of corpuscles, indicating that they were very adhesive. These facts seem sufficient proof of the correctness of the view above expressed regarding the cause of the rouleaux.

The adhesiveness of the red corpuscles does not appear to be a vital property. When the fibrine has been removed from a drop of blood during the progress of coagulation, the rouleaux will form again, after being broken up, as many times as the experiment is repeated, until the blood becomes thick from dryness ; and if evaporation be prevented by Canada balsam placed round the plate of thin glass, with suitable precaution against the approximation of the two plates, the rouleaux will remain perfect for several days (e. g. fourteen in one experiment of the kind), after which the very slow chemical action of the balsam upon the blood gradually renders it confusedly red and opaque. Gum mixed with blood seems to preserve it, like a pickle, from decomposition for a very considerable period ; and if a piece of wet lint be suspended above such a specimen so as to prevent evaporation, the corpuscles will retain then- adhesiveness for a long time (e. g. twenty-four days in one instance), until the water communicated to the mixture by the artificially damp atmosphere gradually renders them non-adhesive. These experiments were made in winter, when the low temperature prevents rapid decomposition ; but it appears unlikely that even at that period of the year a part of the human body should retain any vital properties after having been left three and a half weeks mixed with strong gum, which, it is to be observed, alters very much the form and appearance of the corpuscles.

Both in man and in the frog the white corpuscles also are found aggregated together more or less in a drop of blood examined microscopically, and indeed they adhere much more closely than the red ones both to the glass and to one another ; but as they are not disc-shaped, but globular, they do not become grouped into rouleaux, but into irregular masses, which, in consequence of their colourless and transparent character, are apt to pass unnoticed, or to be mistaken for masses of coagulated fibrine. If a portion of blood be allowed to run in between two plates of glass nearly in contact with one another, the white corpuscles will be found sticking together near the edge of the glass at which the blood entered, the blood having been as it were filtered of white corpuscles as it passed on ; and this is not due to the greater size of the colourless corpuscles than the red, for I have seen it occur with frog’s blood when there was room enough between the plates for the red corpuscles to lie edgewise, then- tx-ansverse dimensions being greater than the diameter of a white corpuscle.

650 MR. J. LISTER ON THE EARLY STAGES OE INFLAMMATION.

The red corpuscles also often adhere to the colourless ones.

It will be seen hereafter that the corpuscles of blood within the vessels of the living body present great varieties of adhesiveness, according to the amount of irritation to which a part may he subjected; such variations are also met with in hlood outside the body, in consequence of differences in the quality of the plasma.

If a drop of very thick solution of gum-arabic, freshly prepared and free from acidity, be added to about fom- drops of blood, the red corpuscles of the mixture will be found to aggregate much more speedily and more closely than those of ordinary blood, a fact ascertained some years ago by Mr. Whabton Jones and some other observers *. The result is the formation of dense orange masses with large colourless interspaces, but without much regular appearance of rouleaux. On closely examining such a specimen, the red discs are seen to be much diminished in breadth and increased in thickness, and exhibit an extreme degree of adhesiveness, sticking together indifferently hy their edges, or any other parts that happen to come first ; and if one of the masses be stretched so as to break, the separating corpuscles become drawn out into long viscid processes, which at length give way in the middle, and each half is drawn into its respective corpuscle.

This remarkable effect cannot be accounted for by the mere viscidity of the plasma, which would not make the corpuscles adhere to each other more intimately than usual, unless they had themselves experienced some change, of which, indeed, then- altered form is conclusive evidence. Further, if a very small quantity of acetic acid be added to the gum before mixing it with the blood, the corpuscles will be found to have lost altogether their adhesive character, although the mixture may be made viscid to any degree that may be desired. A little acid perspiration on the finger appears to prevent entirely the formation of rouleaux in a drop of blood taken from it ; but after the finger has been washed, the usual appearances present themselves when more blood is dram. Diminished adhesiveness of the red corpuscles is also the earliest evidence of the chemical action of tincture of cantharides and croton oil on the blood of the frog. A similar effect is produced when a drop of human blood is shed into a little fresh almond or olive oil on a plate of glass, and stirred slightly so as to break up the hlood into minute drops. On microscopic examination of such a mixture, one sees the red discs aggregated as usual in the interior of the larger drops ; but at their exterior, which is in contact with the oil, and throughout the smaller drops, the corpuscles are somewhat altered in form, being of less diameter, but thicker, though still in the form of discs, and at the same time they are found to have lost every trace of a tendency to adhere together ; and when present in a thin layer of blood they stand apart at equal distances from one another, as if exercising a mutual repulsion, at the same time exhibiting molecular movements. If a drop of blood freshly shed upon a glass plate be stirred with a needle in an atmosphere of chloroform vapour, the rouleaux will be found to form less perfectly in proportion to the time that the chloroform has acted, until, if the period be as long as * Guy’s Hospital Reports, vol. viii. p. 73.

MB. ,T. LISTElt ON THE EAKLY STAGES OF INFLAMMATION.

thirty seconds, the corpuscles will be all cup-shaped, and will exhibit no disposition to aggregate. But no effect is produced on the formation of the rouleaux by stirring a drop of blood in the same way for a much longer time in an atmosphere free from chloroform. The aggregation of the corpuscles is not prevented merely by their becoming cup-shaped, and therefore unable to apply themselves to each other as usual. For the vapour of caustic ammonia, while it renders the corpuscles cup-shaped, seems rather to increase than to diminish their adhesiveness and aggregating tendency, and a temperature of about 32° Fahk. has similar effects with the alkali*. Even in the mixture of blood and gum many of the corpuscles are cup-shaped, though adhering together with peculiar tenacity.

Whether or not it will ever be possible to explain these curious facts upon chemical principles seems very doubtful ; but in the meantime, what appears most striking about them, and what most concerns the present inquiry, is that great effects may be produced upon the adhesiveness of the red corpuscles, both in the way of increase and diminution, by very slight changes in the chemical qualities of the plasma.

The galvanic current produces no effect upon the aggregation of the red corpuscles, either of man or of the frog, as I have ascertained by placing the fine platinum wire extremities of the poles of a powerful battery a short distance from one another between two slips of glass beneath the microscope, then completing the circuit by shedding a drop of blood between the plates, and immediately observing the result. In several such experiments I invariably found that aggregation took place as usual, and the only effect produced by the galvanism was a chemical change in the blood, dependent on electrolysis, gradually developing itself in the immediate vicinity of the poles, and causing solution of the corpuscles.

* Since this paper was read, I was told by a gentleman well known in the scientific world, that he had observed, many years ago, that if blood was shed upon a plate of glass previously heated to the temperature ot 100°Fahh., the red corpuscles showed no disposition to aggregation till the glass cooled, when the blood became killed, as he supposed, by the unnaturally low temperature. This appeared to me entirely irreeoncileable with the fact, that in the frog the red corpuscles aggregate immediately after the blood has been shed, although there is no material difference between the temperature of the air and that of the body of the animal. But, if true, it would have important bearings, to which I need not here allude, upon the essential nature of inflammation. I have therefore thought it well to make some experiments upon the point. The plate ol glass upon which the blood was to be placed was warmed by immersion in water of a known temperature, and quickly but carefully dried. A drop of blood from my own finger was then at once shed upon it, and without loss of time covered with a piece of thin glass, which had been kept warm by being laid upon a metallic plate of the same temperature as the water. By proceeding in this way, I was able to make observations upon the blood very soon after it had been shed ; and when the glass was about 100° Fahr., the aggregating tendency was found j ust the same as in ordinary cases, and I detected short rouleaux already formed within five or six seconds of the escape of the blood from the vessels of the finger. The same state of things continued when the water was as high as 136° ; but when its temperature was carried up to 155°, the red corpuscles lost their disc-shape and some of them appeared to become broken up, and no rouleaux were formed either while the blood remained warm or after it had cooled. From these results, it is evident that heat does not interfere at all with the aggregating tendency of the corpuscles, unless it is sufficiently great to act upon them chemically.

ME. J. LISTER ON THE EARLY STAGES OF INFLAMMATION.

The bully coat in inflammatory blood was first explained by Mr. Wharton Jones*, who showed that it resulted from the red corpuscles aggregating more closely than usual, and therefore falling more rapidly through the lighter plasma, so as to leave the upper portions completely before the occurrence of coagulation. It was supposed by the same authority that this peculiarity of the red discs was due to increased fibrine in solution, rendering the liquor sanguinis abnormally viscid, and so operating like the. admixture of gum above alluded to. But the fact that the corpuscles aggregate as closely after the fibrine has been removed as before, appears quite opposed to such a view. I have examined many drops of my own blood, before and after the removal of its fibrine, with the special object of ascertaining this point, and have never been able to detect any material difference between the aggregation in the two sets of cases. In the blood of the bat before mentioned, which was probably suffering constitutionally from inflammation, the corpuscles continued to retain their excessive adhesiveness for a whole hour after coagulation of the fibrine. I once made a similar observation on a specimen of horse’s blood f , which, as is well known, presents the buffy coat in the state of health. Having divided the clot vertically several hours after coagulation had occurred, my attention was attracted, on looking at the section, by minute red points, like grains of sand, lying in the lower part of the buff, just above the coloured portion of the coagulum. On microscopic examination of a small piece containing some of them, they proved, as I expected, to be masses of aggregated red corpuscles, but with the peculiarity of being compact and globular instead of presenting the usual appearance of a network ot rouleaux, and it was evident that the corpuscles had been excessively adhesive at the time when aggregation took place. Some of the red discs were now squeezed out from the fibrinous mass in which they lay, and as they escaped into the surrounding serum they at once adhered firmly in that fluid, forming again compact globular masses, such as, if in freshly-drawn blood, would necessarily give rise to the buffy coat ; so that their adhesiveness seemed to have been in no way affected by the withdrawal of the fibrine from solution. It may of course be urged, that the fibrine, when in solution, may have impressed upon the corpuscles an adhesiveness which they retained after soaking for hours in serum, but this seems a very unlikely hypothesis. I suspect, therefore, that the peculiarities of the corpuscles of inflammatory blood are the result of other changes than the excess of fibrine.

From the facts detailed in this section, it appears that the aggregation of the corpuscles of blood removed from the body depends on their possessing a certain degree of mutual adhesiveness, which is much greater in the colourless globules than in the red discs ; and that, in the latter, this property, though apparently not depending upon vitality, is capable of remarkable variations in consequence of very slight chemical changes in the liquor sanguinis.

» British ami Foreign Medical Review, October, 1842.

f This observation was made subsequently to the reading of the paper, viz. in November, 1867.

mb. j. lister on the early stages oe inflammation.

SECTION II. On the Structure and Functions of the Blood-vessels

An acquaintance with the anatomy and physiology of the vascular system is indispensable to a successful study of the deviations from health exhibited in the circulation of the blood through the vessels of an inflamed part; it is not, however, intended to give here a full account of the subject, but merely to dwell upon some important points on which differences of opinion prevail.

It has long been a debated question whether or not the capillaries possess contractility, and there is still some difference of opinion among authorities upon the subject. With a view to throwing light upon this important point, I investigated carefully the structure of the minute vessels of the frog’s foot ; dissecting them out from between the layers of skin composing the web, so as to render their constituent material capable of clear' definition with the microscope. The chief results have been communicated to the Royal Society of Edinburgh, in a paper that will shortly appear in their Transactions, "On the Structure of Involuntary Muscular Fibre*.” I need therefore merely repeat here, that while the capillaries were proved to consist, as has been long known, merely of a delicate homogeneous membrane beset with occasional nuclei, the minute arteries, some of them even less in calibre than average capillaries, were found to possess three distinct coats, namely, an external layer of cellular tissue, in variable quantity, longitudinally arranged, an internal extremely delicate lining membrane, and an intermediate circular coat, which constituted the principal bulk of the vascular parietes, and which, when highly magnified, was found to consist of a single layer of muscular fibre-cells, each wound spirally round the internal membrane so as to encircle it from one and a half to two and a half times.

Now when we consider the properties of muscular fibre-cells, which, as is shown in the paper referred to, are capable of contracting in the pig’s intestine as much as to onetenth of their length, it is impossible to conceive a more efficient mechanism for the constriction of a tube than is provided in these minute arteries. On the other hand, the capillaries are totally destitute of any structure known to be contractile. The changes of calibre which occur in the vessels of the living web are in perfect harmony with this anatomical description ; for while the arteries, even to their smallest branches, are sometimes constricted to absolute closure, and at other times widely dilated, the capillaries are never found to be entirely closed, nor to present any variations in diameter, which are not explicable by elasticity of their parietes-}-.