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2,760

1,080

7,450,000

16,960

2,700

1,110

coarsely granular leucocytes in mm. blood.....

11.45-12 noon. Lesion established in right pleural cavity.

1 P.M. Temperature, 364°. Respiration, 40. Sp. gr. of blood from ear...

Hæmoglobin value...

Sp. gr. of blood serum....

Number of chromocytes in mm. blood

leucocytes in mm. blood....

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coarsely granular leucocytes in mm. blood..

2.30 P.M. Temperature, 37.2°. Respiration, 32. Sp. gr. of blood from ear....

Hæmoglobin value..

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coarsely granular leucocytes in mm. blood..

6.30 P.M. Temperature, 39.2°. Respiration, 34.

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coarsely granular leucocytes in mm. blood....

1.0545

45

1.029

7,100,000

39,120

⚫ 2,600

610

1·0545

46
1.0285

7,600,000

44,410

2,415

585

1.0495 41

1.028

6,840,000

48,560

2,530

138

Autopsy made at 7 P.M. revealed no hemorrhage; I suspected the fall in the specific gravity might be due to hæmorrhage, and so performed autopsy at once to see the seat of it. There was a not very copious exudation into the pleural cavity; the pleural surface showed patches of inflammatory cells, but among these not many coarsely granular were found in my examination of them.

It is noticeable that, although the apoplasmia of the blood was here absent, there was, nevertheless, a great reduction in the number of coarsely granular leucocytes, not merely relatively to the rest of the leucocytes, but absolutely per unit volume of blood.

In the experiments with the ligation of a piece of intestine and mesentery, the apoplasmia developed later than in the other series. Copeman and myself* have noticed that in the rabbit the operation * Loc. cit., and 'Journ. of Physiol.,' vol. 14, p. 52.

of ligation of the vessels of the spleen, and various other forms of experimental interference with the contents of the abdominal cavity, including even the simple opening of the cavity by an incision through the linea alba, are all followed by increase in the specific gravity of the blood. In these cases there occurred increase in the specific gravity usually detectible in thirty minutes or less from the completion of the operation. I was therefore somewhat surprised to meet so long a latent period for the reaction in the case of the ligation of the intestine or mesentery of the dog. But in the rabbit interference with the abdomen so disturbs the normal respiration (in rabbits respiration is almost entirely abdominal) that complications arise which are far more considerable than in the dog; e.g., in the rabbit the blood pressure often exhibits under these conditions a considerable temporary depression, and the respiratory rate is very greatly hurried. W. Hunter* has observed in this animal an increase of specific gravity of the blood to follow interperitoneal transfusion. By Copeman and myself it was suggested that this inspissation of the blood is a concomitant, or even a symptom, of "abdominal shock." Subsequent observations by Mr. Grünbaum and by myself, but especially by Professor Roy and Dr. Cobbett, have confirmed its association with abdominal operations, but I would now extend its scope to a large number of other inflammatory lesions.

(II.) Changes in the Total Number of the Leucocytes.

That the number of leucocytes per unit volume of circulating blood is increased in many cases of acute local inflammation is a fact established by the researches of numerous observers. Some of the most recent and detailed observations on this point are by v. Limbeck+ and by Rieder. They supply careful measurements of the degree of this " inflammatory leucocytosis." With a number of their observations my own are fully in accord. In two respects, however, our observations do not agree.

V. Limbeck states that leucocytosis always commences prior to the occurrence of any inflammatory exudation; the exudation is a result of the leucocytosis; to my mind his observations do not prove the fact. Certainly, from a number of my experiments, I should conclude rather the reverse, because the blood became obviously apoplasmic prior to any increase of the number of leucocytes in it. Löwit,§ in discussing Limbeck's and Rieder's observations, remarks *Journ of Physiol.,' vol. 11, p. 115.

Arch. f. Heilkunde,' vol. 10, p. 392, 1890.

'Beiträge z. Kenntniss d. Leukocytose,' Leipzig, 1892. Rieder gives a very complete review of previous observations and opinions on "inflammatory leucocytosis;" I will not, therefore, recapitulate them here.

§ Op. cit.

that, although the fact is not mentioned by them nor obtainable from their measurements, he would expect a diminution in the number of leucocytes in the circulating blood to precede the leucocytosis. I have a number of observations which demonstrate the accuracy of this supposition by Löwit. It seems the rule for inflammatory leucocytosis to be preceded by a leucocytopenia (Löwit's term). This preliminary leucocytopenia of the blood is the more remarkable when, instead of the number of leucocytes per unit volume of blood, the numerical ratio of leucocytes to chromocytes is studied. If the total number of leucocytes remained the same there would, as a result of the apoplasmia at this time, appear to be an increased number of them per unit volume of blood.

The degree of leucocytosis which occurred in the experiments was often very considerable. The number of leucocytes per unit volume of blood was in some instances increased sevenfold. A small part only of such an increase as this can be accounted for by the coexisting degree of apoplasmia of the blood. The highest ratio of leucocytes to chromocytes observed in my experiments has been 1: 136, a proportion corresponding very closely with the highest observed in Löw it's experiments, dealing with another form of leucocytosis, viz., that following intravenous injection of albumoses, &c. But the ratio 1 : 136 was observed in the dog, and is not nearly so abnormal a ratio as the ratio 1 : 140 observed in one of the experiments on the pleural cavity of the cat. Löwit experimented on rabbits, so that my ratios are not strictly comparable with his. The largest number of leucocytes met with per c. millimeter of blood has been in my experiments 55,000, the number at the outset of the particular experiment being 7,750.

The statement by v. Limbeck,† supported by Gottlieb Pick, that inflammatory leucocytosis does not appear in inflammations accompanied by slight exudation, but accompanies those causing marked exudation, has not been found to hold good in my experiments, e.g., in case of inflammation in pleural cavity hardly any exudation but marked leucocytosis.

Frequently the leucocytosis is followed by a final leucocytopenic phase (cf. Example on page 175). This does not always occur, but it is occasionally very marked. I have only seen it happen when the temperature has fallen below normal, and the exitus lethalis is not far off. In one instance the leucocytes fell to less than 2000 per c. millimeter.

Op. cit.

+ 'Zeitschrift für Heilkunde,' vol. 10, p. 392, 1890.
'Prager Med. Wochensch.,' 24, p. 303, 1890.

(III). Disturbance of the numerical Ratios normal between the

various kinds of Hamic Leucocytes.

Before attempting to consider the nature of the upset produced in the ratios normal between the various sets of leucocytes in the blood, it seems necessary to give some characteristics of the different sorts of hæmic leucocytes I have endeavoured to distinguish. The confused condition of the terminology applied to the subject has led of late more than once to the misapprehension of an observer's descriptions. This I would hope to avoid by prefacing my summary with a short account of the varieties of hæmic leucocytes which I have studied.

I have for the present confined the observations requiring the sorting of the leucocytes to experiments on the dog and cat. I wish it to be understood that, except where distinctly otherwise stated, this brief description is applied to the blood of those two species.

The classification followed has been based on that by Wharton Jones, who was the first to discriminate varieties of white bloodcorpuscles in the blood, the "finely granular" and the "coarsely granular." Some years later Rindfleischt and then Max Schultze‡ corroborated Wharton Jones' separation of the two kinds of cell, and through the work of the last authority the distinction became widely known. M. Schultze noted besides the above certain other " smallest and "small" kinds of leucocytes. These I have followed him in keeping apart from the "finely granular" of Wharton Jones; them, together with certain of the large leucocytes, I put into a class recognised by all recent observers as scarcely at all granular, and therefore conveniently termed "hyaline" (M. Foster).§

A. The Finely Granular Leucocyte.

Large or medium in size, rarely small. Nucleus almost always obscured when the living cell is spheroid and unstained, but obvious when the cell is spread and crawling, or when half dead or tinged with nuclear dyes; the nucleus is usually polymorphous or polymerous, the lobes of it usually (almost invariably) united by bonds of chromatin. The irregularity of the nucleus is not a sign of reproduction nor of degeneration. It is, as Arnold|| first suggested, and a number of later observers (Korschelt, ¶ Dekhuysen,** Gulland,+t

* Op. cit.

+ 'Pathologische Histologie,' 1861.

Op. cit.

§ Text-book of Physiology,' Part I, p. 47, Edition 6.

Archiv f. Mikroskopische Anatomie,' vol. 30, p. 226, 1887.

¶'Zool. Jahrb., Abtheilung f. Anat. u. Ontogenie der Thiere,' vol. 4, 1889.

** 'Verhandlungen d. Anatom. Gesellschaft,' 1890.

†† 'Lab. Rep. Roy. Coll. Phys., Edin.,' vol. 3, 1891.

M. Heidenhain*) succeed in proving, a sign and result of the amoeboid activity of the cell. If the cell is allowed to quiet slowly down before it is killed, I have shown that the nucleus then very usually returns to spheroidal form. Of course the cell body becomes spheroidal much sooner than the nucleus. In the slowly killed cell the nucleus usually becomes excentric in situation as well as spherical in shape. It is also especially liable to smear. In the counting solution the nucleus of this cell does not tinge so readily as does that of the hyaline leucocyte. Under certain circumstances, when kept for a number of hours in vitro, the nucleus of this leucocyte frequently presents a curious appearance I have not found described. The appearance is shown in figs. 6 and 7 (Plate 1). A number of portions of the nucleus are set in a wreath-like manner around the approximate centre of the cell. I have never observed this arrangement in the nucleus of the coarsely granular or hyaline leucocyte.

Cell body: finely granular. The granulation of the cell body has been called "neutrophil" by Ehrlich, Rieder,§ &c. In the cat, under the prolonged action of aqueous methyl blue solutions, some granules, especially in the neighbourhood of the nucleus, take on a bright rose tint, and ultimately a considerable amount of rosecoloured substance in rounded masses, some of large size, appears in the cell. But the cell is much altered when this happens, and a good deal of plasmoschisis has gone on. With less departure from the normal a good deal at least of the granulation of this cell can by pushing eosin or rubin be coloured by these acid dyes; Kanthack and Hardy consider them, strictly speaking, oxyphil.

This cell is amoeboid. I have previously pointed out that at low (16° C.) temperatures, it appears to be more amoeboid than is the coarsely granular leucocyte. If kept for an hour or so in hanging drop at 42° C. this cell shows well the "excroissances sarcodiques" of Dujardin, that, as Ranvier¶ has pointed out, are not to be confused with pseudopodia. Besides the quaint fixed finely granular excrescences there are protruded from the cell at a slightly lower temperature, quickly rising, clearer, vesicular-looking processes; these are thrust out in succession from various points of the periphery, one falling as a later rises. They lead to no locomotion of the cell. I mention them here because I have never seen the coarsely granular leucocyte or the hyaline leucocytes produce either of these excrescences, although under the same conditions, and in the same

Kern u. Protoplasma,' Leipzig, 1892.

+ 'Proc. Internat. Congress of Physiologists,' Liège, 1892.

‡'Arch. f. d. Physiologie,' 1879; 'Zeitsch. f. klin. Medicin,' 1880; later papers § Op. cit.

Loc. cit.

Traité Technique d'Histologie,' p. 156.

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