Value of the schilling hemogram in infections: Preliminary report based on 3500 cases

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<ul><li><p>VALUE OF THE SCHILLING HEMOGRAM IN INFECTIONS </p><p>PRELIMINARY REPORT BASED ON 3500 CASES* </p><p>ARTHUR A. EISENBERG, M.D., AND HARRY S. NEMENS, M.D. </p><p>NEW YORK CITY </p><p>KIinischer and h;immatoIogischer Be- fund miissen zusammengehen.-NaegeIi. </p><p>T 0 paraphrase CIaude Bernards weII- known dictum : true science teaches us to doubt and, in ignorance, to </p><p>refrain, we may say that true science shouId teach us to doubt and try, whiIe ignorance teaches us to doubt and refrain. </p><p>About four years ago one of us (A. A. E.), feeIing that more information couId be obtained from bIood counts, if the Iatter were performed according to the method of SchiIIing, began to use this method routineIy. </p><p>In presenting this preIiminary report and our impression we are conscious of both quantitative and quaIitative inade- quacies, an entireIy insuffIcient number of cases representing the former, and an in- sufhcient number of counts on the same case constituting the Iatter; we feeI, how- ever, that even a smaI1 number of cases, if suffIcientIy diversified, permits us, if not to draw concIusions, at Ieast to admit impressions. </p><p>The data herein gathered wiI1 probabIy make very IittIe impression on that type of cIinician, be he a surgeon or a physician, whose majestic seIf-assurance is ever un- rumed, come what may. In an exceIIent articIe by Yagudal there is this quotation of HeIIwig : FowIers opinion that it is diff%uIt to estimate the exact diagnostic vaIue of the Ieucocytosis, is at the present time as true as it was in Igoo. Tt is hardIy possibIe to beIieve that any one couId, even with the most superficia1 knowIedge of clinica hematoIogy, make such a state- ment today; yet Yaguda quotes a number of men, some of them we11 known, whose opinion of the vaIue of bIood studies to </p><p>the surgeon is entireIy negative. We must, therefore, bow to the fact that there wiI1 aIways be a group of cIinicians who wiI1 refuse to accept the newer facts (we em- phasize the word facts) discovered by modern hematoIogy, and who wiI1 continue missing, now and then, an occasiona diagnosis, taking out an inoffensive anemic appendix which had never done anyone any harm, or Ieaving in the so-caIIed siIent suppurative appendices, or mak- ing sanguine prognosis onIy to find them- seIves confronted with the sudden death of that particuIar patient who had been doing so we11 right aIong. </p><p>There is, however, another group of chnicians who have not made a fetish of cIinica1 judgment, infaIIibIe and error- proof; who weIcome any heIp which has, as its soIe object, the desire to shed Iight, whenever possibIe, on an obscure diagnosis, or on an uncertain prognosis; to add an eIement of certainty when diagnosis is wavering, and to sound a warning when compIications arise before they manifest themseIves cIinicaIIy. To this group of cIinicians who are aIways on the qui vive, who form a weIcoming vanguard to a new fact or thought and who do not shut the windows to prevent a ray of Iight from entering the cIinica1 judgment, to this group we dedicate the resuIts of our investigations. </p><p>I. THEORETICAL </p><p>Adumbrating the summary at the end of the article we wish, at the outset, to point out the folIowing impressions which, we beIieve, are justifiabIe: </p><p>I. The quantitative and quaIitative studies of the Stab-zeflen or, as we, in </p><p>* From the Pathologica Laboratories of the Sydenham Hospital, New York City. </p><p>56 </p></li><li><p>NEW SERIES VOL. XXI, No. 1 Eisenberg, Nemens-SchiIIing Hemogram A ,nericnn .Jr,l,rnnl of srgcT,y j - </p><p>common with many others, have desig- nated them, band or staff ceIIs, are the most important parts of a bIood count. It is in the recognition of the existence and of the importance of the band ceIIs, the im- mature neutrophiIes with non-segmented nucIei, that the SchiIIing2 count (the written record of which is caIIed a hemo- gram j differs from an ordinary count. </p><p>2. The band ceI1 count study is even more important in conjunction with the tota Ieucocyte count and, as has been again recentIy emphasized by MedIar,3 with the mature, i.e. segmented, neutro- phiIes, for it is the mutua1 reIationship of these three eIements: the tota Ieucocytic count, the number of the mature (seg- mented) and of immature (band) neu- trophiIes, that reflects, mirror-Iike, the hematoIogica1 reaction in the presence of infection. </p><p>3. By infection we understand not onIy diseases caused by bacteria and their toxins, but aIso a11 pathoIogica1 conditions in which there is abnorma1 cIeavage or breaking down and hyperabsorption of proteins, e.g. intestina1 obstruction, de- generated uterine myofibromata, uIcerat- ing maIignant neopIasms, etc. </p><p>4. In many. deep-seated infections, cen- tra1 pneumoma, deepIy buried retroceca1 appendicitis, etc., a properIy performed bIood count is of inestimabIe vaIue in that it pIainIy and unequivocaIIy points to the existence of a progressive infection, not onIy hours, but not infrequentIy, days, before the symptoms and signs permit one to form a definite cIinica1 diagnosis. </p><p>5. A SchiIIing hemogram is of the greatest vaIue in postoperative or meta- critica recovery from a surgica1 or medica infection; the arising compIications are reflected first (and often considerabIy earIier) in the bIood count. We have seen patients who were discharged with a high band count (15-20 per cent*) onIy to re- turn again within a few days, some with intestina1 obstruction or peritonitis, others with empyema. We have become used to </p><p>* The norma band cel1 count is 3-S per cent. </p><p>seeing patients who, whiIe doing fine, wouId suddenIy show an aIarming bIood picture whiIe, cIinicaIIy, the reason for it wouId become obvious onIy some time, hours or days, Iater. </p><p>6. We have Iearned to appreciate not onIy the quantitative but the quaIitative changes in the band ceIIs. In severe infec- tions the usua1 form of the band ceI1 nu- cIeus is that of a sausage, very plump and Iarger than in moderate infection; very frequentIy the nucIeus is riddIed with vacuoIes, whiIe the cytopIasm is studded with the so-caIIed toxic granuIes, large, dark and pIeomorphic. </p><p>7. In a very smaI1 percentage of cases, not over I per cent, no hematoIogica1 expIanation of the surgica1 picture found at the operation couId be vouchsafed, this discrepancy consisting both of the absence of hematoIogica1 evidence of infection in the face of an adequate anatomica pathoIogy, and of the absence of definite pathoIogica1 changes in the presence of a suggestive bIood picture (here we might add that there may have been patho- IogicaI changes, but not demonstrated b\ Iaparotomy). </p><p>Theoretical Basis of the Schilling Hemo- gram. The epoch-making studies of Ar- neth (1904) which have estabIished the morphoIogica1 variabiIity of the nucIeus of the neutrophiIic Ieucocyte, have natu- raIIy focussed attention afresh on the significance of the bIood count. </p><p>True, Arneths4 own method has not and, probabIy wiI1 not, become an everyday Iaboratory procedure for several reasons. In the first pIace, Arneths count is too compIicated: there are five cIasses of ceIIs, according to the number of the nucIear Iobes, each of which has four or more con- figurations ( sausage, bean, baI1 ), giving a tota of over twenty different neutrophile ceIIs; the amount of time con- sumed by such counts is not the onI), objection; during the Iast twenty-five years Arneth has engaged in probabl&gt;- more poIemics than any other hematolo- gist, on pureIy theoretica grounds, and </p></li><li><p>58 4 merican Journal of Surgery Eisenberg, Nemens-SchiIIing Hemogram JULY, 1933 </p><p>IargeIy because he had gone too far in estimating the vaIue of his cIassification. SchiIIing, Weidenreich, Pappenheim and Tuerk are some of his adversaries. One of the most serious arguments against accepting Arneths teaching Iies in the fact that he disregards the degenerative (quaIita- tive) changes in the cytopIasm as we11 as in the nucIeus (the presence of toxic granuIes, vacuoIes, staining defects, etc.), in other words, he ignores a11 those changes which have been so we11 studied, recentIy, by GIoor.5 For other objections to the accept- ance of a11 of Arneths tenets the reader is referred to the numerous articIes by SchiIIing, GIoor and others. </p><p>In order to cIearIy understand SchiIIings conception of the bIood picture, it is usefu1 to recaI1 severa physioIogica1 data. </p><p>In the mammalian bone marrow circuIa- tion is cIosed (Doan, Sabin,6 Cunningham, Drinker). The ceIIs produced in the bone marrow are the erythrocytes, the throm- bocytes (bIood pIateIets) and the granuIar Ieucocytes: the eosinophiIes, the basophiIes and the neutrophiIes; whiIe the erythro- cytes are formed intravascuIarIy, the Ieucocytes are formed extravascuIarIy; after the maturation has progressed from the myeIobIast, through the promyeIocyte to the myeIocyte, and from the myeIocyte to the metamyeIocyte, the active migra- tion of Ieucocytes into the bIood vesseIs begins; in other words, normaIIy the metamyeIocyte is the first Ieucocyte to enter the vesseIs, due to the streaming of its granuIes; during this penetration a few metamyeIocytes change into the band ceIIs, of which a11 but 5-8 per cent mature into the segmented neutrophiIes (mature neu- trophiIic Ieucocytes) in the periphera1 circuIation, and thus a drop of bIood taken from the Iatter gives us the weII-known normal differentia1 formuIa of 70 per cent neutrophiles (62-65 per cent of segmented, and 5-8 per cent of band ceIIs), 20-25 per cent of lymphocytes, 1-2 per cent of eosinophiIes, 0.5 per cent of basophiIes and 3-4 per cent of monocytes (the Iym- phocytes being formed by the lymphatic </p><p>tissue, and the monocytes by the reticuIo- endotheIia1 tissue). </p><p>The deIivery of the ceIIs from the bone marrow to the bIood stream takes pIace, according to Shaw, in two tides, one beginning in the forenoon, reaching its height in the afternoon and decreasing earIy in the evening, whiIe the other tide begins Iate in the evening, reaches the maximum shortIy after midnight and the minimum in the morning; these diurna1 variations affect the tota count but not the differentia1 percentages. These facts shouId be carefuIIy evaIuated when check- ing up the bIood counts made on the same patient at different hours, in order to do justice both to the patient and to the one who examines the bIood. </p><p>The infectious agent apparentIy intro- duces either both a chemotactic and a maturation factor or a chemotactic factor onIy; in the former case a Ieucocytosis with a norma differentia1 count resuIts, whiIe in the second case there wiI1 be, after a transitory Ieucocytosis, a progressive Ieucopenia, due to the fact that a Iast- ing chemotaxis wiI1 graduaIIy Iead to exhaustion. </p><p>The exact mechanism of these two opposing factors is not yet known; it may be, as Noy and EppIer beIieve, that the stimuIus to the bone marrow Iies not in the direct chemotaxis by bacteria or their toxins, but in the increase of the body substances which normaIIy stimuIate the bone marrow; it may be that the norma spIenic inhibitory hormone reIaxes during the infective process, or it may be that with the increased phagocytosrs a new stimuIus for an increased production of the neutrophiIes is furnished; at any rate, whatever the stimuIus, it is a specific one for the neutrophiIes, since the baso- phiIes and, particuIarIy, the eosinophiIes promptIy disappear at the onset of infec- tion, and reappear when the Iatter is gone. </p><p>What reguIates the dehvery of the Ieucocytes under norma conditions? It is assumed that normaIIy the production of the myeIoid Ieucocytes (the neutrophiIes, </p></li><li><p>N,-, sElllEs vOL. XXI, No. I Eisenberg, Nemens-Schilling Hemogram A merican Jour~~:~l 01 Surgery 59 </p><p>basophiIes and eosinophiIes) is reguIated, directIy or through the sympathetic nerv- ous system, by hormones; at Ieast one of them seems to be produced by the spIeen, and appears to be an inhibitory one; it is a matter of everyday cIinica1 observation that most of chronic spIeno- megaIies (Bantis disease, maIaria, chronic tubercuIosis, syphilis, Gauchers and Pick- Niemanns diseases, WerIhofs disease, pernicious anemia, etc.), except the Ieuke- mias, are accompanied by Ieucopenia; some subacute spIenomegaIies (e.g. typhoid fever) are aIso characterized by Ieucopenia. </p><p>NaegeIi has recentIy expressed an opin- ion that the resuIting bIood picture, both quantitative and quaIitative, in infections, i.e. the toxic reaction of the bIood, depends IargeIy on the degree of mesenchyma1 affinity of the bacteria concerned in a gi\.-en infection, pointing out that whiIe the coccaI infections produce intense changes in the bIood pictures, infections which seem to have a marked prediIection for the ectoderma1 nervous tissue (neurotrophic or neurophilic infections), such as Heine- Medin disease, tetanus, lethargic encepha- Iitis, etc., are not reflected by any marked changes in the bIood picture. </p><p>A word in connection with the spIenic inhibitory hormone; it must be added that a11 other ceIIuIar eIements produced by the bone marrow: the erythrocytes and the thrombocytes (bIood pIateIets), are aIso under the spIenic contro1, and E. Frank stresses the finesse and deIicacy of the contro1 manifesting itseIf beautifuIIy in the fact that spIenectomy causes an in- crease onIy or especiaIIy of that bone marrow eIement, the insuffIciency of which constituted the most striking part of the preoperative hematoIogica1 picture; thus, in pernicious anemia it is the erythrocytes, in !\erIhofs disease the bIood pIateIets (the thrombocytes), and in Bantis disease the Ieucocytes which so strikingIy increase in numbers. </p><p>In passing we may mention Stephens opinion that it is the adrena cortex which, together with the spIenic hormone, controIs </p><p>the hemopoietic functions of the bone marrow. </p><p>FinaIIy, there arises the question of whether the spIenic hormone controIs the production of the ceIIs or their maturation and reIease into the periphera1 circuIation; it is quite conceivabIe that the Iatter two phenomena may be under the pIurigIandu- Iar contro1 of the endocrines, so that the spIenic hormone controIs the production of the immature Ieucocytes, and the endo- crines their maturation to neutrophiIes, and the substances Iiberated by the dead, disintegrated neutrophiIes (which sub- stances are probably chemotacticaIIy iden- tica with bacteria1 toxins) reguIate the outflow of new neutrophiIes to repIace them. </p><p>To transIate the foregoing physioIogica1 data into the cIinica1 hematoIogica1 picture, we may say that if the infection introduces both the chemotactic and the maturation eIements, we shaI1 have a Ieucocytosis and a norma differentia1 count, if the infection is slight; if the infection gains, the neutro- phiIes, both the band and the segmented ceIIs, wiI1 increase, as wiI1 the tota Ieu- cocyte count; if the infection becomes severe, the maturation of the band ceIIs into the segmented neutrophiIes wiI1 Iag, and the percentage of the band ceIIs wiI1 rise, and that of the segmented ceIIs wiI1 decIine; from now on, as the infection gain...</p></li></ul>

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