Histology of the Blood, Normal and Pathological

s with v

also takes the nuclear stains, and possibly is to be considered an accessory nucleus. We have received the impression that we have here to deal with a vacuole filled with substance secreted by the cell. In a large series of preparations, it is possible to obtain some elucidation of the development and fate of these appearances.

taining cells is 15-20% of th

cal lymp

t of human lymphocytes as described above. They

inophil, vacuole containing cells, and lymphocytes, and could thus demonstrate that in uncomplicated cases of removal of the spleen, where inflammatory processes, accompanied by an increase of the polynuclear

brought about by two quite different factors: (1) by a diminished production of lymphocytes, (2) by an increased influx of polynuclear forms, which naturally lowers the relative count of the lymphocytes. It was therefore necessary to obtain a method which would show alterations in the absolute number of the individual forms of leucocytes. Kurloff used for this pu

udo-eos. 10% lym

h after the opera

ures were supplemented by the following averages

= 19.8 pseudo-eos.

81 " 18.

puscles had about doubled itself, but that in this increase the lymphocytes exclusively

imals whose spleens had been removed, may be illustrated by one

,000. Number of white 10,700. On April 19, 1888, the spleen was removed, the wound healed by first

the percentage proportions ran somewhat differently. The percentages rose from 35 to 66% for the lymphocytes only, whilst for the other forms they distinctly fell: for the nucleated from 44% to 22% and for the large mononuclear from 18% to 9%. It was only in the course of the second year that a very considerable relative and absolute increase of the eosinophil cells appeared: the values rose gradua

page 89. The figures in the char

otal number

line-ly

f nucleated, pseud

-large mono

ne-eosino

BL

o col

o-eosinop

ympho

mononucl

sinoph

rosinop

mparative

ls Lymphocytes Large mononuclear cell

es % On comparative surfaces % On comparative surface

8

44.7 - 35.4 - 1

7 35.6 8.5 21.6 5

3.6 32.6 9.1 18.0 5

6 40.3 11.3 14.3

.5 47.7 14.3 10.3

.0 35.0 12.2 23.6

9 44.4 13.3 18.4 5

9.4 49.3 16.2 20.0

3 49.0 16.2 20.0 6

9 52.3 19.3 14.5 5

8 56.4 23.7 11.7 4

9.2 57.1 31.9 25.6

59.1 30.1 21.8 11

0 66.4 45.8 15.7 1

.6 67.2 38.9 9.5 5

0.7 65.4 34.6 12

11.3 67.3 34.9 9.7

11.7 65.3 33.5 9.8

4 16.3 64.4 39.9

13.0 66.4 38.5 9.6

8

29.8 - 53.3 - 1

20.0 50.1 35.6 12.9

18.9 44.2 27.4 15.2

22.0 38.3 24.1 11.3

8

6.5 30.1 15.3 11.1 5

17.5 24.5 11.7 9.4

eat in tabular form, shew that in this experiment No. I. we are

mber of white b

he end of the first year At

0 14,20

0 27,60

0 19,20

2,600 20,

of the single kinds of white corpuscle

e end of the first year At

mb

t

pe

lear granular

es

ear

lear granular

es

ear

lear granular

es

ear

p

7 4232 1568 2101 17

5464 16615 2980 2539

0 6568 10041 3686 9

hes we draw the fo

for the guinea-pig, since that animal bears splenectomy witho

tantly that it may be looked upon as a characteristic sign of the absence of the spleen. This increase may amount to double and more. We must therefore assume that the deficiency of splenic function may be met by the lymphatic glandular system. T

conditions these cells are met with exclusively in the bone-marrow, and that inflammation in animals after removal of the spleen is accompanied by an acute pseudoeosinophil leucocytosis, exa

w, we must assume that normally also the bone-marrow is responsible for the majority of this kind in the blood, and that the deficiency in the splenic contribution can be easily covered by a slightly r

nteresting, and leads to a really enormous rise in their absolute and relative numbers. Their percentage number once rose to 34.6%

ectomy in the first year compensation occurs only in the lymph-glands, followed in the second year by a great increase of the eosinophil cells. It is to be particularly insisted

off's observations, which might be regarded as depend

cally studied for a period of years. We have ourselves begun our observations in two patients directly after the operation, but were unable to continue them, as death occurred within the first week after the extirpation. Up to the present only seven cases of rupture of the spleen with subsequent splenectomy

stigation showed a considerable lymph?mia: the bulk of the lymphocytes belonged to the larger kinds: the eosinophil cells were certainly not

er described. We made counts in oldish and fresh preparations. It is worthy of notice that this case is not u

he followi

uclear Lymphocytes Eosi

892 81.9%

1892 80.0% 1

897 56.8% 33

month after the operation, and had lasted for a very long time, just as Kurloff has found in some animal experiments. Just as little as a polynuclear increase is abnormal, is an increase of the lymphocytes remarkable; and in this case the lymphocyt

ic cysts, since the part of the spleen not affected by the cyst formation often shews quite a normal structure, and therefore is physiologically active. On the other hand, the excisi

ht about by the increase of the lymphocytes, as is seen from the results of Credé and the table contained in his paper. It is further remarkable that four weeks after the operation a painful doughy swelling of the whole thyroid appeared, which remained, with variations, for nearly four months. With the general recov

urs is from Hartmann and Vasquez. As the result of their r

red blood corpuscles and a true acute hyp

corpuscles sinks at first but reco

lymphocytosis of varying

months, a moderate

able to investigate t

spleen was removed by E. Hahn on account of an echinococcus on Feb. 5, 1895. One may well assume that before the opera

ar neutro

cytes

ophil

ononucl

cells

thisis pulmonum existed at the time, to which we must attribute an increase of the polynuclear elements, a

irst intention. The white blood corpuscles were permanently increased. The proportion of white to red was 1:120 to 1:130, the average number of red was 3,000,000. Our own examination of preparations obtained some two months after the operation, shewed

was no considerable increase of the lymphocytes. The eosinophils on the contrary were increased distinctly, the mast cells to a lesser extent. It is probable that the increase of both of the latter kinds of

leen. The latter present great difficulties, for one never knows how far in the most

tion of the lymphatic glands may be excluded, shoul

the liver, neoplasm in the cranial cavity, and in which the numbers of the eosinophils amounted to 12.3%, 7.0%, 6.5% respectively. In three cases of acute splenic tumour in typhoid fever the figure 0.31% with a maximum of 0.82%, was found. These authors have already raised the question "whether the increase of the eosinophil cells i

ubt can now remain that the question has

terial is not quite lost for the organism. Thus Ponfick has found that after destruction of the red corpuscles the spleen takes up a portion of their "shadows," and for this reason calls the splenic tumour a spodogenous splenic tumour (σποδο?, ruins). Ehrlich has made a corresponding obse

only to a very small degree. In the spleen of normal mice nucleated red blood corpuscles are seen in relatively large numbers; in the rabbit they are less numerous and often only to be found with difficulty. In the dog they only make their appearance after an?mia from loss of blood, normally they are absent. In the human spleen nucleated red blood corpuscles are not to be found normally or in cases of severe an?mia, but exclusively in leuk?mic diseases. U. Gabbi in his recen

in no respect be considerable, and that if these cells really are produced by it, they must be free from granulations. The spleen therefore stands functio

Lymphati

from contributing to the formation of the blood, we are dependent almost entir

nds, are identical with those of the lymphatic glands and the rest of the lymphatic system. This is proved by the complete agreem

thors. For example, Reinbach describes several cases of malignant tumour, particularly sarcoma, in which the percentage of lymphocytes, which normally amounts to about 25%, was very considerably lowered; in one case of lymphosarcoma of the neck they only made up 0.6% of the total number. These conditions are quite easily and naturally explained by the exclusion of the lymphatic glands. It is dif

other leucocytoses, relatively seldom. Under certain conditions in which a hyperplasia of the lymphatic glandular apparatus makes its appearance, we often see at first an increase of the lymphocytes in the blood. Ehrlich and Karewski

a in a rare skin disease, chiefly from the absolute increase of the lymphocytes alone, although no swelling of the glands was palpa

belongs to this category, since a vicarious enlargement o

f the lymphocytes to polynuclears is practically normal in the leucocytosis of digestion, indeed the lymphocytes are rather in excess. The eosinophils on the other hand shew a marked relative reduction in this condition. The leucocytosis of digestion consequently differs essentially from t

s. A considerable increase of the lymphocytes in the blood-stream is here to be observed. Thus Weiss found an important increase o

vulsive period of this disease both the polynuclear cells and the lymphocytes are increased, the latter in preponderating amount. The former cells are increased to twice

tosis. In quite isolated cases, an increase of the lymphocytes in the blood in consequence of the injection of tuberculin into tuberculous individuals has been seen. (E. Grawitz.) From the rarity of these cases it can scarcely be doubted

producing a lymphocytosis. Waldstein asserts that he has produced by injection of pilocarpin

ntestinal diseases of children, we refer it to the excitation of the lymphatic apparatus of the intestine, in tuberculin lymph?mia we recognise mainly a reaction of the diseased lymph glands. Hence we conclude that a lymphocytosis appears when a raised lymph circulation occurs in a more or less extended area of lymphatic glands, and when, in consequence of the increased flow, more elements are mechanically washed out of th

e polynuclear leucocytes possess lively am?boid move

e vessel wall. A very interesting experiment on this point was described by Neumann years ago. Neumann produced suppuration in a patient with lymphatic leuk?mia, in whom the blood contained only a very small number of polynu

cells; nevertheless this does not in the least prove that these lymphocytes have emigrated here from the blood vessels. This is not the place to enter into the very extensive controversy on this point. We are content to refer to the most recent very thorough

rvations on inflammatory processes, that the lymphocytes are in no way connected with the po

e Bone

hese authors showed that the early stages of the red blood corpuscles are produced there; a discovery which was quickly and generally recognised, and which soon became pathologically useful through the observations of Cohnheim and others. In thi

are in the production of erythrocytes. The type which the normal blood formation follows in adults, and the deviations therefrom shewn in pernicious an?mia, have been described in the ch

er of animals (for example the monkey, guinea-pig, rabbit, pigeon and so forth) the bone-marrow exhibits the peculiarity that the cells it produces be

of the bone-marrow

fferent tinctorial and morphological properties. Man and monkey for example have neutrophil granulation; guinea-pig and rabbit the pseudo-eosinophil granulation described by Kurloff; in

ral dyes respectively; they shew a much smaller affinity for the basic dyes. The fact that they greatly exceed t

ebrate series from the frog to man, and which therefore are not characteristic for any

lear cells of different type. They are not nearly so numerous, or so importa

he mammalian class. According to the recent researches of Pugliese the giant cells are considerably increased after extirpation of the sple

s pass into leucocytes by amitotic nuclear division. Unfortunately in his prelim

ges of development, from the mononuclear through the transitional to the polynuclear (polymorphously nucleated) forms, which we meet with in the circulating blood. A glance a

ripening can be seen in the po

rked as the cell grows older. The pseudo-eosinophil granules of the mononuclear cells, of the guinea-pig for example, stain bluish-red in eosine-methylene blue after long fixing in superheated steam: in the transitional stages this admixture is gradually lost, and finally completely va

ipening of the cell may proceed more rapidly than that of the granules. It is particularly easy to observe this point in eosinophil cells. Ehrlich had already mentioned in his first paper (1878) that side by side with the typical eosinophil granules isolated granules are often found which shew a deviation in tinctorial properties: for instance, they stain more of a black colour in eosine-aurantia-nigrosin; in e

ve acceleration of the morphological ripening of the c

s of the bone-marrow. The mononuclear and transitional forms of the neutrop

lymph glands, and for this reason named them "myelocytes," κατ' εξοχην[16]. When myelocytes, no matter of what size, appear in considerable numbers in the blood of an adult, a

il myelocytes, occur, almost exclusively, in leuk?mic blood. These forms, which were first recognised by H. F. Müller, are however o

rrow, as Ehrlich has always insisted with all distinctness. It is only on this assumption that the frequently sudden appearance of leucocytosis, as has so often been observed in morbid and experimental conditions, can be satisfactorily explained. In these cases the space of time, amounting often only to minutes, is far too short for a new formation of leucocytes to be

finite injurious influences which affect the organism may be quickly and energetically combated. Just as in a fir

leucocytosis; in leucocytosis of high degree their relative number may indeed be lowered, in consequence of the exclusive increase of the polynuclear cells. It

the guinea-pig only the pseudo-eosinophil polynuclear cells are increased, which wander as such out of the bone-marrow, but not the polynucleated non-granulated forms, which but slowly grow to maturity in the blood. Thus the peculiarities of guinea-pig's blood, in which two kinds of polynuclear cells are recognisable, throw light upon the corresponding conditions in hu

as to the places of formation of the no

spleen, but that after extirpation of the spleen the absolute number does not change. The bone-marrow then

cked out in the medley of the different kinds of cells only with the utmost difficulty, owing to their small number and their but little characteristic properties. Consequently an exact investigation of their origin could probably only be successful if it were pos

the most important of the blood-forming organs, for its function is the exclusive production of r

rative enumerations of the arterial and venous blood of a bone-marrow area. J. P. Roietzky working under Uskoff's direction has recently made counts of this kind in the dog, from the nutrient artery of the tibia and the corresponding vein. He found that the number of white corpuscles of the vein is s

orpuscles Ripe corpu

00 1950 (13%) 840

6 (4.0%) 2788 (17

s that the function of the bone-marrow is continuo

e rate of the circulation. All evidence indeed tends to shew that on the contrary the bone-marrow performs its functions discontinuously, inasmuch as elements continually grow to maturity in the bone-marrow, as we have

hich considerable portions of the bone-marrow are replaced by tissue of another kind. We may best divide the obse

rarer are the cases in which as is necessary the whole bone-marrow has been subjected to an

ures of a simple severe an?mia; but in addition isolated normoblasts, small marrow cells, and moderate leucocytosis. The autopsy, at which the whole skeletal system was subjected systematically to an exact examination, shewed a complete atrophy of the bone-marrow, and replacement of the same by the t

e of metastatic carcinoma of the bone-marrow, there was found a considerable an?mia, with numerous nucleated red blood corpuscles both of the normo- and megaloblastic type; their nuclei presented the strangest shapes, due not merely to typical nuclear division, but also to nuclear degeneration. The white

adjacent tissue in specially strong concentration, and also in a negatively chemiotactic manner on the wandering cells. This view receives support from the careful work of Reinbach on the behaviour of the leucocytes in malignant tumours. Out of 40 cases examined, in only one, of lymphosarcoma complicated with tuberculosis, were myelocytes found in the blood, amounting to about 0.5-1.0% of the white blood corpuscl

they arise on the contrary, according to our view, when a specific morbid agent acts upon the bone-marrow, as we must assume is the case in the pernicious forms of an?mia. In the cases of an?mia from

th megaloblasts, and yet only very scanty examples are to be found in the blood. Whether the emigration of the megaloblasts from the bone-marrow into the bloo

generally confirmed. In these cases extensive tracts of bone-marrow are replaced not by masses of malignant growth but by an indifferent tissue, so to speak, a tissue which is unable to exercise the above-described stimulating inf

al growth of the lymphatic tissue takes place very rapidly, and for this reason brings about a quick and uncomplicated exclusion of the bone-marrow tissue; as it were, experimentally. Under its influence the neutrophil elements of the bone-marrow vanish rapidly, and in many cases so completely that

report; and he similarly explains the absence of neutrophil cells in ly

exceedingly surprising that Fr?nkel, after accurately examining and analysing eight cases of acute lymphatic leuk?mia, believes he has found in them imperative reasons for th

ng process. It is easy to conceive any particular stimulus or injury bringing about an acceleration of the normal process, that is, a premature old age, but it is equally difficult to represent clearly to oneself conditions which retard or completely prevent the normal ageing of the elements. The discovery of such conditions would be really epoch-making, both for general biology, and for therapeutics. The only escape from this dilemma would be the assumption of a very premature death of the lymphocytes, for which however not the smallest evidence is to be found, even in Fr?nkel's monograph.

TNO

pleen, an assumption which Engel himself does not once appear to make, since he expressly warns against drawing any conclusions from this name as to their origin. Since, however, the acute leucocytoses, as we shall shew in the next sec

ast cell granulation side by side. That this is certainly not the case is shewn by the fact that the "basophil" granulat

ever, diphtheria, typhoid. They were performed in the following way: dry cover-slip preparations were made from the juice of the glands removed shortly after death, and were stained in the usual way by Ehrlich's triacid mixture. Amongst a large number of cases thus examined, it was possible in only one case of scarlet fever-but in this beyond all doubt-to demonstrate the presence of mononuclear cells with neutrophil granulation." The extreme rarity of this condition sup

is author performed his experiments, contains in all races of dogs-according to the information very kindly given us by Pr

il cells, since according to Ehrlich's postulates this absence of

ormation of the other blood-forming organs, especially of the lymph glands is found; a transformation suffici