Original Articles.THE ORIGIN AND NATURE OF THE BLOOD
PLATES.BY JAMES HOMER WRIGHT, M.D., S.D.,
Director of the Pathological Laboratory of the Massachusetts GeneralHospital; Instructor in Pathology, Harvard University MedicalSchool.
A prolonged study of the comparative mor-
phology of the blood corpuscles of a wide rangeof animals has shown me that all of the manytheories hitherto proposed concerning the originand nature of the blood plates are untenable anderroneous.
In this paper I shall not set forth my reasonsfor coming to this conclusion, but I shall confinemyself to a brief statement of my own opinionsconcerning the origin and nature of these bodiesand a summary of the facts and observations uponwhich my opinions are based.
By means of a staining fluid,1 devised by me foruse in the staining of blood films according tothe method of Leishman, which gives the so-called Romanofsky polychrome staining, I havebeen enabled to stain characteristically the bloodplates in sections of fixed tissues and organs sothat they may be positively recognized and maybe clearly distinguished from other histologicalelements. The description of the method ofobtaining suitably stained sections with thisfluid is reserved for a later publication.
After an extensive study of sections of bonemarrow and other tissues in which the blood platesare thus characteristically stained, I have con-vinced myself that the blood plates are detachedportions of the cytoplasm of those giant cells ofthe bone marrow and spleen which have beennamed " megakaryocytes " by Howell to distin-guish them from the multinucleated giant cellsof the marrow
—
the so-called osteoclasts or poly-karyocytes (Howell).
This idea of the origin and nature of the bloodplates is based upon the following observations:
In the sections, the blood plates (Figs. 7, 11and 12) present the following characteristics:They appear as small bodies of generally circularoutline, of a variable diameter but usually lessthan that of an erythrocyte; a striking character-istic is the presence in the central part of eachplate of an aggregation of more or less closelypacked, minute, red to violet stained granuleswhich may be so closely packed together and so
deeply stained as to form an opaque, homogene-ous, sharply outlined mass giving an appearancesuggestive of a nucleus. In this central portionof the plates of some animals small, rounded,unstained, vacuole-like areas are often present.The marginal portion of the blood plate is trans-lucent, blue stained and, though sometimeshaving a smooth edge, it usually presents at theperiphery indentations and short projections ofirregular shape giving the edge an irregular or
jagged or fimbriate outline. There is thus to bedistinguished in the blood plate two portions,namely, a central, granular, red to violet stainingportion and a marginal, homogeneous, hyaline,blue staining portion. The diameter of thecentral portion and the width of the marginalportion vary, the latter being usually narrowerthan the diameter of the former.
The giant cells present the following peculiari-ties which are of importance for the subject ofthis paper:
The cytoplasm making up the central andusually the greater portion of the giant cell iscrowded more or less densely with closely set,minute, red to violet granules, for the most partlike those of the central portions of the bloodplates, while at the periphery it is hyaline andblue stained. This hyaline peripheral portionforms a definite narrow zone of somewhat variablewidth, but is veiy narrow as compared with thediameter of the whole cell and has a smooth or
finely ragged or fimbriate edge. In appearanceit suggests the ectosarc of an ameba. Themajority of the giant cells are of spherical form,but a minority are of varied and irregular shapeby reason of the distortion of their cytoplasminto processes and pseudopod-like prolongationsof varying length, form and width, so that theypresent all the varieties of form and outline shownby a motile ameba (Figs. 1, 2, 6, 10 and 13).
Some giant cells may be observed in whichnearly all of the cytoplasm is in form of pseudopod-like processes extending peripherally in variousplanes from a small central mass of cytoplasmsurrounding the nucleus (Figs. 4 and 14). Inthese distorted giant cells the central red toviolet granular portion of the cytoplasm is con-tinued into the pseudopod-like processes toform in them a central portion, and the peripheral,hyaline, blue, marginal zone also continues on tothese processes as a hyaline marginal zone witha smooth, or finelv ragged, or fimbriate free edge(Figs. 1, 2, 4, 6, 10, 13 and 14). These pseudo-pods of the giant cells may have in some in-stances a greater length than the diameter of thefield of an oil immersion objective. Their widthis never less than the diameter of the smallerblood plates. They may be seen sometimes pro-jecting far into the lumen of a blood vessel throughits imperfect wall (Figs. 1, 6, 10 and 13). Someof them are seen unconnected with anv giant cells(Figs. 3, 5, 7, 8, 9, 11 and 12), and such freepseudopods have been found not only in the bloodchannels of the marrow and spleen, but also in thecapillaries of the lungs.
A comparison of these pseudopods, especiallythe slender ones, with the blood plates shows themost striking similarity in composition andstructure (Figs. 5, 7, 8, 11 and 12). The materialconstituting the granular, red to violet staining,central portion is like the granular, red to violetstaining, central portion of the plates in color,texture and general appearance. It may alsocontain small, round, unstained, vacuole-likespaces like those seen in the central portions ofthe plates (Figs. 5, 7, 11 and 14). The hyaline
1 A Rapid Method for the Differential Staining of Blood Films andMalarial Parasites, by James Homer Wright, M.D., Journ. Med.Research, vol. vii, p. 138, January, 1902.
Pathological Technique, by Mallory and Wright, third edition,p. 370. Saunders, Philadelphia, 1904.
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marginal zone of the pseudopod is also just likethe marginal hyaline portion of the plate intexture, staining, width, and outline of its edge.
Moreover, in a few pseudopods, of a widthcorresponding to the diameter of the blood plates,one or more short lengths of the central, red,granular portion may be seen to be marked offby constrictions or to be definitely separated andto appear as rounded masses or segments of thesame diameter and with the same appearances asthe central portions of the blood plates (Figs.1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12 and 14). Suchseparate, rounded masses thus are completelysurrounded by the hyaline material constitutingthe marginal zone of the pseudoped and theappearances are thus produced of a typical bloodplate with its hyaline marginal portion continuouswith the hyaline marginal portion of the pseu-dopod; or of a pseudopod formed out of a shortchain of blood plates by the continuity of theirmarginal portions.
Furthermore, there may be observed short bud-like pseudopods springing, either directly fromgiant cells or from other pseudopods, with rounded,central, granular portions, either separate from,or continuous with, the central granular portionof the main mass of cytoplasm (Fig. 13). Thesmaller of these bud-like pseudopods are also inevery respect like blood plates, except that theyare obviously a part of the cytoplasm of a giantcell.
In brief, the two constituents of the cytoplasmof the pseudopods and of the bud-like processesof the giant cells are identical with the twosubstances making up the blood plates in stain-ing reaction and texture and they are similar intheir arrangement with reference to each other.Furthermore, all grades of transition exist be-tween bud-like processes of giant cells in processof detachment (Fig. 13), or slender pseudopodsshowing signs of dividing into smaller parts bytransverse division and the blood plates (Figs.1, 2, 3, 4, 5, 7, 8, 10, 11, 12 and 14).
In view of these facts the inference seems tobe justified that the blood plates are detachedportions of the cytoplasm of the giant cells. Thisidea derives additional support from the follow-ing considerations:
1. That the giant cells do lose their cytoplasm.This is shown by the relatively small amount ofcytoplasm of some of the giant cells exhibitingameboid forms, and by the occurrence of degen-erate looking-giant cell nuclei with little or no
cytoplasm connected with them (Fig. 4.) Theappearances seem to clearly indicate that thisloss of cytoplasm occurs chiefly by the detach-ment of buds or plate-like fragments or seg-ments from pseudopods, or of whole pseudopods,rather than by disintegration and liquefaction,evidence of which may be seen in some giant cells.
2. The number of giant cells and pseudopodsin which the appearance of plate formation ispresent is only a small proportion of the wholenumber of giant cells and is not greater than couldbe expected at any given moment in view of thenumbers of the blood plates.
3. The direct observation by me of protoplas-mic movements of identical character, both in thehyaline marginal zone of the giant cells and inthe hyaline marginal zone of the blood plateson the warm stage of the microscope. Thesemovements have been described by Detjeenand others for blood plates. I have seen thehyaline marginal zone of the giant cells and ofthe blood plates constantly changing its outline,sending out and withdrawing short processes ofvarious shapes. The so-called ameboid move-ment of the blood plates is not surprising, be-cause it is known that detached fragments ofliving protoplasm may exhibit independentmovement.
In this connection I may state that I haveseen a few giant cells change their form verymarkedly, sending out and withdrawing pseu-dopods, such as are seen in the sections. Thisseems to show that the presence of pseudopodsand protoplasmic prolongations of giant cellsand even of whole giant cells in blood vessels,as I have seen in the sections, is not a passiveact, due to local conditions of pressure in thetissue, but is a manifestation of the vital activityof the giant cell.
4. According to my own and others' observa-tions, bodies that are undoubtedly and obviouslyblood plates are found only in the blood ofmammals, and mammals are the only creaturesthat have giant cells in the blood forming organs.I have found undoubted, characteristically stain-ing blood plates in the blood of all of a consider-able variety of mammals including the opossumand camel, and I have found giant cells in theblood forming organs in all mammals, includingthe opossum, in which I have sought for them.The so-called spindle cells or fusiform corpusclesof the birds, amphibia, reptiles and fishes havebeen claimed by some writers to be the morpho-logical equivalents of blood plates, but mystudies of the blood of these vertebrates havenot led me to accept this view.
5. It would seem from my own observationsand from the studies of others that the bloodplates make their first appearance in embryonicmammalian blood at about that stage of develop-ment when the giant cells have first appeared inthe blood forming organs. This point, however,is not as definitely established as I could wish.
6. A comparison of the results of the enumera-tion of blood plates, obtained by Helber and byPratt in certain pathological conditions, withthe histological findings in the bone marrow inthe same diseases suggests a relationship betweenthe blood plates and the giant cells. Thus inpernicious anemia and lymphatic leukemia theblood has been repeatedly found to contain ab-normally few plates, while the marrow in typicalcases of this disease, as far as can be inferredfrom the reports in medical literature and frommy own observations, undergoes profoundchanges in the character of its cellular constitu-ents with resulting very marked diminution inthe number of the giant cells. On the otherhand, in post-hemorrhagic anemia, the blood
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Origin of the blood plates from the giant cells of the bone marrow.
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plates are increased in number and there is alsoincrease in the amount of red marrow with goodevidence that the number of giant cells in theblood forming organs are relatively and abso-lutely increased in number.
In so-called myelogenous leukemia the bloodplates are also increased in number,and in the cellu-lar accumulations of this disease giant cells do notseem to be an uncommon finding, although butlittle attention has been paid to them by path-ologists. In view of the enormous increase in themarrow elements in this disease it must beobvious that the presence among them of a rela-tively small proportion of giant cells means a
great absolute increase in the number of suchcells in the body.
My acknowledgments are due to Dr. OscarRichardson, assistant pathologist, for relievingme of much of the regular work of the laboratoryduring the period in which I have carried onthis study.
description of plate.
The photomicrographs were made by Mr. L.S. Brown in the Pathological Laboratory of theMassachusetts General Hospital from sections ofthe bone marrow, spleen and lung of the cat, theblood plates of which animal are especially large.The magnification in all the figures is approxi-mately 1500 diameters.
Fig. 1. Giant cell with a pseudopod projectinginto a small blood channel of the bone marrow.A blood plate in process of pinching off is seenat the free extremity of the pseudopod. Thegranular portion of the cytoplasm is denselystained. The hyaline margin of the pseudopodis only faintly shown.
Fig. 2. Giant cell with a pseudopod projectinginto a blood channel of the bone marrow. Otherpseudopods either free or attached to the cell arealso shown. Two small rounded bodies near thepseudopods in the vessel are either blood platesor cross sections of pseudopods.
Fig. 3. Detached pseudopod in a capillary ofthe lung in process of segmentation into bloodplates.
Fig. 4. A small pseudopod segmenting intoplates and still attached to a nearly naked giantcell nucleus in a blood vessel of the spleen.
Fig. 5. Blood plates and detached pseudopodsin a blood vessel in the spleen.
Fig. 6. A giant cell with pseudopods, two ofwhich stretch far into a small blood channel ofthe marrow. The continuity of one of themis not visible in the figure.
Fig. 7. Blood plates and a detached pseudopodin process of segmenting into blood plates. Thevacuole-like unstained areas in the central por-tions of the pseudopods and of the plates areshown. Two leucocytes are present.
Fig. 8. Detached pseudopods showing seg-mentation and transitions to blood plates. Theselie in a small blood vessel of the marrow.
Fig. 9. Small detached pseudopod showingindications of segmentation in a lung capillary.
Fig. 10. Giant cell in the marrow with pseudo-
pod protruding into a blood vessel through itsthin wall. The free portion of the pseudopodhas segmented so as to form a short chain ofthree blood plates connected together by theirhyaline marginal portions.
Fig. 11. Thrombus-like mass of blood plates ina vessel of the marrow. Among the plates twodetached pseudopods, one of which shows signsof beginning segmentation. Vacuole-like un-stained areas are seen in some of the blood platesand in one of the pseudopods.
Fig. 12. A detached pseudopod, several bloodplates, a few erythrocytes and three leucocytesin a blood vessel of the spleen. The hyalinemarginal zone, both of the pseudopod and ofsome of the plates, is fairly well shown.
Fig. 13. A giant cell of the spleen with a
pseudopod projecting into the lumen of a smallblood vessel through its wall. At the free ex-
tremity of the pseudopod two plates are seen inprocess of formation.
Fig. 14. Giant cell in a blood vessel of thespleen with its cytoplasm nearly all arranged inpseudopods and more or less detached from thenucleus. Some blood plates are seen either freeor in continuity with the pseudopods. Vacuole-like unstained areas are shown in the mass ofcytoplasm at the left of the nucleus.
INFLAMMATION OF THE FRONTAL SINUS.*BY HARRIS PEYTON MOSHER, M.D., BOSTON.
Headache is asymptom which in a great manyinstances receives the most off-hand diagnosis asto its cause and the most off-hand treatment.The case is much like that of the crying baby andthe soothing syrup. There is a sure remedyalways at hand. It is on every dressing tableand on the show case by every soda fountain.We are taught that cause and effect aways gotogether and so should be studied together. Inthe common symptom of headache, however, theeffect often engrosses our attention to the exclu-sion of the cause. It is a truism, of course, butone which I shall take the liberty of repeating,that an eliminating diagnosis of the cause ofrecurring and chronic headache requires a mostthorough, sustained and systematic physicalexamination plus a keen cross examination of thepatient's personal and family history and a
judicial weighing of the testimony thus secured.This means that the broad knowledge and soundgood sense of the general practitioner must attimes be supplemented by the examinations of theman doing special work, and it means that bothshould work together; and that the specialist inmedicine like the specialist in finance should tryto keep out of "fads and fancies."
The subject of this paper is acute and chronicinflammation of the frontal sinus. The chiefsymptom of disease of the frontal sinus is head-ache. I ask your permission to make what I haveto say a little informal and in the line of a demon-
*Read before the Lawrence Medical Club, April 23, 1906.Charts and specimens from the Anatomical Laboratory of the
Harvard Medical School.
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