Leukocyte Formula of Blood

LEUKOCYTE FORMULA OF BLOOD, the percentage relationship of the five individual types of leukocytes: neutrophils, eosinophils, basophils, lymphocytes, and monocytes. The leukocyte formula of blood is compiled on the basis of counting 200-300 leukocytes in a stained blood smear. (Regarding the technique for compiling the L. f., see Hemogram.) The L. f. is subject to significant fluctuations even in healthy people, namely: Types of leukocytes In % Neutrophils...........j 60-75 Eosinophils........... 2-5 Basophils............0.5-1 Lymphocytes...........j 25-35 Monocytes........... In absolute numbers 4,200-5,250 140-350 35-70 1,750-2,450 350-560 (The calculation of the absolute number of individual types of leukocytes is based on 7,000 leukocytes in 1 mm³.) The table presented does not reflect the L. f. in children. According to data processed by the method of variation statistics by Kononova, the L. f. of newborns 2 hours after birth is almost identical to the L. f. of placental blood and is characterized by significant neutrophilia and a left shift of the nucleus; neutrophilia decreases by the 4th day after birth (see table in the article Leukocytoses). Later, the L. f. of an infant changes: neutrophilia decreases, giving way to lymphocytosis. Thus, according to data by Sokolova-Ponomareva, the average figures for individual leukocytes at ages from 1 to 12 months are as follows: eosinophils-3.5%, neutrophils-37.4% (of which [ young 6.6%, stab 4.6%, segmented 26.2%), lymphocytes - 56.4%, large monocytes - 2.7%. With age, the formula gradually approaches that of adults. One L. f. without counting the total number of leukocytes in 1 mm³ of blood does not give a correct picture of the actual ratios of individual forms of leukocytes; the often observed percentage increase in the number of lymphocytes (over 35-40%) does not at all indicate pathological lymphocytosis if the total number of leukocytes is reduced. On the other hand, a normal percentage of neutrophils in leukopenia actually means pathological neutropenia. Thus, only when the total number of leukocytes is known can one, on the basis of the L. f., speak of a pathological increase or decrease of one or another form of leukocytes. The main significance of the L. f. is that from it one can get an idea of the reaction of blood-forming organs to various physiological and pathological processes in the body. In this case, the number of lymphocytes reflects mainly the reaction of lymphoid tissue, the number of neutrophils reflects the reaction of myeloid tissue. Many at the present time share the opinion that the number of monocytes reflects the state of the reticulo-endothelial system, but this opinion cannot yet be considered finally established. The changes in the L. f. observed in clinical practice come down to changes in individual types of leukocytes and represent individual forms of leukocytoses: neutrophilic, eosinophilic and basophilic leukocytoses, lymphocytosis and monocytosis. Neutrophilic leukocytosis, i.e., an increase in the number of neutrophils, is a regular phenomenon in almost all increases in the total number of leukocytes ('neutrophilic leukocytosis'), but can also occur with a normal total number of leukocytes ('neutrophilia'), and sometimes is observed with a decrease in the total number of leukocytes ('neutrophilic hypoleukocytosis'). All pathological leukocytoses, namely-infectious and inflammatory, toxic, posthemorrhagic, tumor, are predominantly neutrophilic leukocytoses. The same is true of the leukocytosis of newborns. Clinical practice at the present time attaches great importance to the combination of data on the total number of leukocytes and the qualitative change in neutrophils. In pathological conditions, changes are observed both in the nucleus, the so-called 'nuclear shifts' (Arneth, Schilling), and changes in the granularity of the protoplasm (Nageli, Freyfeld).- Nuclear shift of neutrophils was first thoroughly studied by Arneth. He divided all neutrophilic leukocytes into 5 main classes according to the segmentation of the nucleus. To class I he attributed neutrophils with a non-segmented nucleus, to classes II-V - neutrophils having respectively 2-5 segments. Arneth also divided these main classes into subclasses. Thus, in class I he distinguished myelocytes (M), neutrophils having a non-segmented nucleus with a slight indentation ('wenig gebuchtete') (W) and with a deep indentation ('tief gebuchte') (T). In classes II-V, Arneth also distinguished a number of subclasses depending on the shape of each segment. Thus, Arneth, in addition to 5 main classes, distinguished up to 80 subclasses. In normal blood, the majority of leukocytes belong to classes II-IV and only a small amount to classes I (3-5%) and V. In most infectious diseases, Arneth observed an increase in the number of neutrophils of classes I and II, i.e., a 'left shift of the neutrophilic blood picture.' A right shift, i.e., an increase in multi-segmented neutrophils, is rare and has much less practical significance. According to Arneth, a left shift indicates an increased entry into the blood from the bone marrow of immature forms of neutrophils, which usually occurs with increased destruction of the most mature neutrophils. Thus, Arneth judged the maturity of neutrophils by the segmentation of the nucleus, considering non-segmented neutrophils young, and the most segmented - the most mature cells; this introduces the basic principle of Arneth's teaching. But in reality, there is often no parallelism between the youth of a neutrophil and the degree of segmentation of its nucleus. The immaturity of a cell is easiest to determine by the structure of the nucleus. A young nucleus, containing little basichromatin, is distinguished by its pale color. In a mature nucleus, basichromatin and oxychromatin are sharply demarcated, and the nucleus appears darker, more differentiated when stained. Myelocytes, attributed to class I, are undoubtedly young cells, but this cannot be said about every neutrophil having a non-segmented nucleus and therefore also attributed to the same class. By the structure of the nucleus, it can be easily established that there are mature neutrophils with a non-segmented nucleus and less mature ones with a segmented nucleus. It can also be considered established that there are no fundamental differences between classes II and V (Pappenheim, Brugsch, Schilling). Thus, Arneth's teaching in its main part is not entirely correct. Moreover, Arneth's classification is so cumbersome that it is practically difficult to apply. At the present time, Schilling's classification is widely spread. It is fundamentally more correct and at the same time much simpler than Arneth's classification. Schilling divided class I (the most important) of Arneth into three groups: myelocytes (M), juvenile (J) and stab (S); classes II-V he combined into one group of segmented (C). Thus, Schilling distinguishes only 4 groups of neutrophils. (For the morphology of myelocytes, see Myelocytes and Leukocytes.) Juvenile neutrophils are characterized by a non-segmented, sausage-shaped or bean-shaped nucleus; this nucleus is not stained intensely, but it is still very clearly differentiated with often strongly protruding nucleoli; their protoplasm b. ch. does not differ from the protoplasm of mature cells, but sometimes has a light blue tint (when stained by Giemsa). This cell is apparently identical with the metamyelocyte of Pappenheim. In normal blood, juvenile neutrophils are found only in single specimens (up to 1%).-- Stab (rod-shaped) neutrophils are characterized by a non-segmented, narrow, band-shaped nucleus of T-, V- or U-shaped form. The structure of the nucleus is clearly differentiated, the nucleus does not contain nucleoli. Such are normal rod-shaped neutrophils; in normal blood they are found in quantities of 3-5%. Schilling also distinguishes 'pathologically-degenerative' forms of rod-shaped neutrophils, characterized by a 'narrow, band-shaped, often strangely curved and always hyperchromic (structureless-dark) shape of the nucleus.'--Segmented neutrophils constitute the largest number of blood leukocytes (60-72%); their nuclei usually consist of 2-5 segments connected by very thin threads or wider bridges. At the present time, the percentage relationships of the four groups of neutrophils described above are almost always included in the L. f. (see also Hemogram). Depending on the ratio of these four groups of neutrophils, Schilling distinguishes the following forms of neutrophilic leukocytoses. 1. Neutrophilic leukocytoses without nuclear shift are observed from physiological leukocytoses during digestive and sometimes static; from pathological leukocytoses - posthemorrhagic, chloroses, polycythemia, in easily infectious processes, in acute polyarthritis (even in severe cases), in tetanus, in uncomplicated malignant neoplasms, after many medications and infusion of physiological solution. Neutrophilia (percentage increase in neutrophils with a normal total number of leukocytes) without nuclear shift is inconsistently observed in chlorosis. 2. Neutrophilia with a simple hyperregenerative shift denotes an increase in the percentage of only rod-shaped forms with a slight increase in the total number of leukocytes.

This form of shift is usually observed in mild acute infections, protozoan diseases (e.g., during an attack of malaria), in superficial and encapsulated abscesses, mild catarrhal appendicitis, in open suppurations of the eye, ear, larynx, in chronic endocarditis, chronic sepsis, in necrotizing malignant tumors, in lymphogranulomatosis, in active, mild tuberculosis, especially of the serous membranes and glands. This form of leukocytosis often has great practical significance, as it helps to confirm latent infection where the process clinically seems cured (e.g., in mild forms of active tuberculosis, chronic sepsis). 3. Neutrophilic leukocytosis with a definitely regenerative shift already denotes some increase in young neutrophils (up to 2-15%) and even myelocytes (up to 1-2%); at the same time, the total number of leukocytes is usually significantly increased. With a greater increase in the number of myelocytes, this shift is called hyperregenerative. This form of neutrophilic leukocytosis is observed in the intensification of all those processes mentioned in the previous group. Among physiological conditions, this form is sometimes encountered during pregnancy and during prolonged muscular work; it is observed in severe intoxications (lead, sublimate, illuminating gas, lysol, phenylhydrazine, etc.), in significant exacerbations of chronic infections (tuberculosis, sepsis and endocarditis), in septic complications of diseases that usually proceed without nuclear shifts or with only a slight or degenerative shift (e.g., typhoid fever, measles, dengue fever, yellow fever, influenza, syphilis, tuberculosis, malignant tumors), also in acute nutritional and digestive disorders in infants. 4. Neutrophilia with a degenerative shift denotes an increase in the number of rod-shaped neutrophils, mainly degenerative forms, not usually accompanied by an increase in young forms; at the same time, the total number of leukocytes is decreased. This form is usually observed in mixed infection (typhoid complicated by sepsis; tuberculosis complicated by secondary infection) and in very chronic or low-virulence cases of sepsis (e.g., relapse of liver abscess, endocarditis). When examining leukocytes for the L. f., the state of the granularity of neutrophil protoplasm deserves attention. In infectious processes, the granularity of neutrophils is often stained very intensely, acquiring the appearance of coarse grains, sometimes separate clumps. Negeli considers such neutrophils to be toxically altered. This so-called toxicity of neutrophils is best revealed when stained not with azure-eosin, but with carbolfuchsin-methyl blue according to Freyfeld. The more pronounced the body's intoxication, the more pronounced the granularity of neutrophils is usually. A neutrophilic, pronounced leukocytosis does not necessarily entail a poor prognosis; it only indicates a sharp intensification of the function of myeloid tissue. On the other hand, slight neutrophilia in diseases that usually proceed with neutrophilic leukocytosis indicates either a mild infection or, conversely, a hypertoxic form; the general clinical picture and sometimes the nature of the nuclear shift help to clarify this. Eosinophilic leukocytosis (eosinophilia). The only acute infectious disease that often proceeds at the height of the illness with an increase in the number of eosinophils along with an increase in the total number of leukocytes is scarlet fever in children. Usually, however, in blood containing an increased number of eosinophils, the total number of leukocytes is not increased, which is why eosinophilic leukocytosis is more often called eosinophilia. Eosinophilia is observed very frequently in helminthic diseases. In trichinosis, eosinophilia is particularly pronounced, reaching even 80%, but in very severe cases of trichinosis, eosinophilia may also be absent. Eosinophilia is often observed in skin diseases: eczema, psoriasis, pemphigus, pruritus; in convalescents in the post-infectious and post-intoxication periods; in anaphylactic and so-called anaphylactoid conditions: serum sickness, hay fever, urticaria, bronchial asthma, colitis membranacea, Quincke's edema; in children - in the so-called exudative diathesis, if the mentioned skin manifestations are present, in approximately 60% of cases; almost regularly in muscular rheumatism, sometimes in lymphogranulomatosis and malignant neoplasms; sometimes in fresh nephrosis, nephritis; rarely in gonorrheal, especially gynecological diseases. The appearance of eosinophils in the blood after their complete absence at the height of the disease indicates the approach of the recovery period (typhoid fever, typhus, etc.). Eosinophilia is often evaluated as a favorable prognostic symptom, but this should be done with great caution. Only in combination with the general clinical picture and other blood changes (lymphocytosis, absence of neutrophil nuclear shift or slight shift, absence of increase in the total number of leukocytes) does eosinophilia have some favorable prognostic significance in acute infectious diseases and chronic tuberculosis. In chronic septic diseases, however, eosinophilia is sometimes observed despite a poor prognosis. In prolonged tuberculosis with fever, the number of eosinophils often does not decrease (Negeli). Basophilic leukocytosis - an increase in the number of blood basophils (normally 0.7%, i.e., up to 40 per 1 mm³). A slight increase is sometimes observed in clinically healthy people. A more significant increase occurs after the injection of foreign protein and after treatment for rabies according to Pasteur. An increase in basophils, varying greatly in degree, is also observed in polycythemia (Negeli), myeloid leukemia, aleukemic myelosis, constitutional hemolytic anemia (Alder), secondary anemia, sometimes in malignant neoplasms proceeding with significant anemia, hemophilia, chlorosis, and in convalescents after beriberi (Schilling). In constitutional hemolytic anemia, the number of basophils does not decrease after splenectomy, just as in myeloid leukemia after treatment with X-rays. In diagnostic terms, basophilia can be used only very rarely. In prognostic terms, it should be noted that only in malignant anemia does a decrease in basophils usually run parallel to the severity of the disease (Negeli). Lymphocytosis - an increase in the number of blood lymphocytes. The evaluation of lymphocytoses must be approached with great caution, as the number of blood lymphocytes is subject to large physiological fluctuations. At the same time, it must be remembered that even after mild infections, intoxications, vaccinations, an increased number of lymphocytes may persist for months. The lymphocytosis observed in many people during and after the war (the so-called war lymphocytosis and 653

"ЛЕЙКОЦИТАРНАЯ ФОРМУЛА КРОВИ"

Post-war lymphocytosis (654), probably stood in connection with nutritional conditions. But even now it is often necessary to observe 30-35% lymphocytes in people without clinically detectable pathological changes. A distinction is made between absolute lymphocytosis (when the number of blood lymphocytes exceeds 3,000) and relative (when only the percentage content of blood lymphocytes is increased). Temporary, transient lymphocytosis may be based on a redistribution factor, as for example myogenic leukocytosis, adrenalin (in certain stages). On the other hand, lymphocytosis in leukemic and aleukemic lymphadenoses occurs as a result of hyperplasia of the lymphatic apparatus. Lymphocytosis as a rule occurs in the post-infection period, as well as post-toxic and in a number of infectious diseases: typhoid fever, epidemic parotitis, smallpox, whooping cough (especially in the catarrhal period), rubella, influenza, malaria, pellagra, dengue fever, chronic benign tbc, syphilis. The origin of lymphocytoses in the just listed group Négeli explains by the increased function of the lymphatic system. This opinion would be correct if in these diseases there was absolute lymphocytosis. In reality, however, only in mumps is there true lymphocytosis, while in smallpox not only lymphocytes but also neutrophils are increased in number, in typhoid and rubella the total number of lymphocytes is either close to normal or somewhat decreased. In most diseases occurring with lymphocytosis there is simultaneously leukopenia, so that the total number of lymphocytes is rarely increased, while the number of neutrophils is decreased. It is therefore more correct to say that for most of these diseases it is not lymphocytosis but leukopenia (see) and neutropenia that are characteristic. Lymphocytoses are also caused by certain exogenous physicochemical influences: prolonged mild effects of X-rays (for example in radiologists), quartz lamps, one-sided nutrition with carbohydrates and fats. Absolute or relative lymphocytosis in combination with neutropenia is observed inconsistently in almost all endocrine diseases (Addison's disease, diabetes, various forms of obesity, etc.). Many consider correct Kocher's opinion that lymphocytosis is characteristic of Basedow's disease; this view needs some limitation, since in Basedow's disease, especially in mild forms and initial stages, lymphocytosis may not be present. It is also not clear whether lymphocytosis in diseases of the internal secretory organs is connected with the endocrine influence on the lymphatic system or whether some other factors play a role here (influence of the autonomic nervous system). The question of the so-called constitutional lymphocytosis is also unclear. Négeli denies the existence of constitutional lymphocytosis, while Bauer recognizes it and considers constitutional lymphocytosis, neutropenia, as a partial infantilism of the blood-forming apparatus, 'as a result of anatomical or functional hypoplasia of the granulocytic system'. Bauer substantiates the role of the constitutional factor in lymphocytic reaction by the facts that certain individuals react with lymphocytosis and not neutrophilia to septic infections (Marchand and others), to purulent tonsillitis (Deussing). The significance of lymphocytosis is often reduced to the fact that it is supposedly a histological expression of the body's immunization (Besangon, Labbé). This point of view is not justified already because, as was pointed out above, lymphocytosis is most often observed in leukopenias and therefore is usually relative. Monocytosis-increase in the number of blood monocytes (normally 6-8%). It must be remembered that in a healthy person monocytosis can also be found if for examination the first drop of blood is taken from the earlobe without preliminary rubbing of the latter (Schilling). Therefore Schilling recommends taking only the second or third drop from the earlobe after preliminary rubbing. Monocytosis is observed both with general leukocytosis and without it. With leukocytosis monocytosis is noted in smallpox, in later stages of typhus, in measles, rubella, epidemic parotitis, acute syphilitic and tuberculous processes, septic processes, many acute infectious diseases (more often in the crisis period); monocytosis is less pronounced in chickenpox, scarlet fever. In typhus the number of monocytes sometimes increases to 20-30%. A sharply expressed monocytosis is sometimes observed in the so-called endocarditis lenta, in which the number of monocytes increases even to 30-40%; at this time special attention is paid to the appearance in the blood of large reticulo-endothelial cells, histiocytes, which sometimes in their morphology are close to monocytes. Without leukocytosis (with normal or decreased total number of leukocytes) monocytosis is observed in protozoan diseases: malaria, kala-azar, relapsing fever, septic processes, the so-called Banti's disease, measles, yellow fever, dengue fever, sympathetic ophthalmia, poliomyelitis, pellagra. In chronic malaria the number of blood monocytes sometimes increases to 40%. Such sharp monocytoses are occasionally observed in anginas (the so-called 'monocytic anginas') and chronic sepses, which some (Marchand, Schultz, Baader and others) explain by specific peculiarities of the causative agents. Although there exists such a causative agent, the so-called Bacterium monocytogenes, with which one can always cause experimental monocytosis in rabbits, however the explanation of monocytic reactions in man exclusively by peculiarities of the causative agent is by no means sufficient; a greater role must be attributed to peculiarities of the macroorganism. As for the origin of monocytoses it must be said that some (Pappenheim and others) tried in the clinic to find evidence speaking for their origin from the lymphatic system, while others (Négeli and others) for their origin from myeloid tissue. However, the increase in the number of monocytes can go parallel either to the increase in the number of neutrophils (for example in sepsis) or to the increase in the number of lymphocytes (for example in protozoan diseases). At present time in accordance with the doctrine of the origin of monocytes from reticulo-endothelial cells (Aschoff - Kiyono) most clinicians look upon monocytosis as a result of the increased functional state of the reticulo-endothelial system. According to this view the histiocytes sometimes encountered in the blood (for example in some septic diseases) are considered to be monocytes. Schilling calls them 'atypical monocytes'. The increased content of these cells in the blood according to some is of central origin, and Schilling could indeed note hyperplasia of reticulo-endothelial cells of the liver, spleen, bone marrow. According to others (Bittorf, Deneke) these cells have a peripheral origin from the endothelium of blood vessels. The view now shared by many about the unity of monocytes and histiocytes, about the origin of monocytoses from the reticulo-endothelial system cannot yet be considered finally proven (Maximov, Bloom). The significance of monocytosis is reduced to the fact that in acute infectious diseases the increase in the number of monocytes, which usually parallels the general increase in the number of leukocytes, usually represents a favorable prognostic sign. This cannot be said in relation to chronic septic diseases. In protozoan diseases monocytosis has diagnostic value.