Erythrocyte Sedimentation

ERYTHROCYTE SEDIMENTATION represents the phenomenon of settling at the bottom of a vessel of erythrocytes when blood is maintained in an uncoagulated state. The varying speed of this process attracted attention in 1917 from the Swede Robin Fahraeus, who observed in the blood of pregnant women the rapid descent to the bottom of the vessel of erythrocytes suspended in blood plasma, and called this phenomenon the instability of pregnant blood. Fahraeus and the German gynecologist Lirzenmeier found in "the old literature indications of the significance of a similar phenomenon, especially in the form of the so-called "inflammatory crust" (crusta phlogistica inflammatoria); it forms during the clotting of blood above the erythrocyte clot when rapid sedimentation of erythrocytes occurs, was described already by Galen and was particularly studied during the flourishing of humoral pathology in the 17th century in the so-called pyrexies; edemas, 67 in severe anemias and many other diseases, but also in normal pregnancy (crusta gravidarum); the crust was considered as materia peccans, and attempts were made to remove it in various diseases by means of repeated bloodlettings. As early as 1792, Henson explained this phenomenon by the accelerated sedimentation that occurred before the blood had time to clot. Later, individual observations on E.S. were described by Nasse, Joh. Muller, Hunter, Biernacki, Ot. Muller, and these authors even partially established the significance of an increase in fibrin in the blood and increased agglutination of erythrocytes for accelerating E.S.; however, systematic research on E.S., which led to a large number of works in the modern literature, is due to the rediscovery of the phenomenon by Fahraeus. Mechanism of the E.S. reaction. Attempts to explain the phenomenon of E.S. purely by physical laws of the fall of erythrocytes in a liquid medium - plasma - proved unsuccessful. If one starts from Stokes' formula, which is used to calculate the speed of fall of equal-sized dense spheres in a liquid, then the quantities entering the formula - radius of the spheres, specific weight of the spheres and liquid, and force of gravity - retain their significance for E.S. (with a correction for the shape of erythrocytes); however, for E.S. other factors have greater importance: fluctuations in the force of attraction or repulsion of individual erythrocytes, their property to agglutinate. At present, decisive importance for the stability of the erythrocyte suspension in plasma is given to the presence of electrostatic forces between the erythrocytes themselves (Fahraeus; Lirzenmeier, Kanai). In the blood, erythrocytes are carriers of electronegative energy; they are negatively charged (Hober): positively charged lanthanum removes their charge, and during cataphoresis erythrocytes move toward the positive pole. The stability of the suspension, which normal blood is, is maintained by the mutual repulsion of like-charged erythrocytes. A decrease in the electronegative charge of erythrocytes lowers the stability of the blood and leads to more rapid E.S. Positively charged protein complexes of plasma, similar to salts of lanthanum, lower the charge of erythrocytes, and E.S. is accelerated. In this sense, fibrinogen acts most strongly, then globulins, while albumins lower the charge of erythrocytes to the least extent. The former view, which attached great importance to E.S. to the viscosity of plasma and the ratio of individual protein fractions (especially fibrinogen and globulins), corresponds to the data of Hebe in that the viscosity of proteins also depends on the degree of dispersion of proteins and decreases in the series fibrinogen-globulin-albumin; thus, the theory explaining the greater or lesser speed of E.S. by the charge of erythrocytes is a generalizing theory. Most authors find an increase in fibrinogen, globulins of plasma with acceleration of E.S. However, there are authors who object to a complete and constant parallelism between E.S. and fluctuations in protein fractions of plasma. Individual authors complicate the explanation of the E.S. phenomenon by introducing new forces, partly corresponding to certain morphological structures, and attach great importance to E.S. to the individual peculiarities of erythrocytes to form agglomerates of varying size in the form of coin columns and agglutinates; Wohlisch recognizes as the basis of accelerated E.S. the adsorption of fibrinogen on the surface of erythrocytes with its transformation into a sticky fibrinogen gel and the formation of delicate elastic threads visible under the microscope, which glue the erythrocytes into clumps. In further stages of E.S., a new factor influences the speed of the reaction: "hemotonia" - the strength of the blood skeleton (from coin columns and other types of conglomerates of erythrocytes), which to varying degrees resists the force of gravity (Balakhovsky). An important factor for the speed of E.S. is the number of erythrocytes in the given blood: in general, erythropenia accelerates, while erythrocytoses slow down E.S. The dependence of the speed of E.S. on the number of erythrocytes was already known to Fahraeus and confirmed by many subsequent researchers. According to Groedel and Hubert, the number of erythrocytes is even the most important factor of the E.S. reaction. At the same time, not only the quantity but also the specific weight of the spheres is of importance; (see below - E.S. in anemias). The number of erythrocytes and the Hb content in the blood being examined must always be taken into consideration when evaluating the results of the E.S. reaction - Lipoids of the blood also have⁷ significance for E.S. Kiirten relates fluctuations in the speed of E.S. to the cholesterol-lecithin coefficient of the blood, namely - cholesterol lowers the stability of the erythrocyte suspension due to its property to remove the charge of erythrocytes, while lecithin has the opposite effect. Grossmann, in lipoidemias after cholesterol loading, observed acceleration of E.S. with an unchanged protein composition of the blood. Clinical material does not give complete confirmation of Kiurten's conclusions, and in part even refutes such a parallelism. As for the influence of plasma salts on E.S., in general sedimentation occurs rather with a lower salt content in the blood than with a higher one; individual ions, according to Klobuzitsky, influence E.S. according to the Hofmeister series. According to Runnstrom, salts of Ca and Ba accelerate E.S. more than salts of K and Na. However, Livshitz observed slowing of E.S. in patients after administration of calcium chloride in various inflammatory conditions. Greater significance have disturbances of acid-base equilibrium, changing the isoelectric point of blood plasma; in this case, a shift toward acidosis slows down, while a shift toward alkalosis accelerates E.S. Stern explains the slowing of E.S. in newborns and the later appearing acceleration by the change from the acidosis of newborns to the alkalosis of subsequent months (depending on the increase of inorganic phosphorus in the blood). Pirogov observed after running a horse slowing of E.S., almost parallel to the decrease in blood pH. When preserving blood in vitro, E.S. slows down due to the

ERYTHROCYTE SEDIMENTATION

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The sedimentation of erythrocytes and the resulting formation of CO₂. Besides these, there are other substances, less studied, which act in a retarding manner on erythrocyte sedimentation and sometimes inhibit sedimentation when added to rapidly sedimenting blood even in minimal quantities. As is clear from the above, the complex mechanism of erythrocyte sedimentation depends on very diverse factors, and it is impossible to explain the fluctuations in the rate of sedimentation by any single cause. In the presentation given, individual moments are arranged according to the degree of importance currently attributed to them. It should be emphasized that the properties of plasma are more important than the properties of the erythrocytes themselves, which has been confirmed by experiments of Linzenmeier, Abderhalden, and many others with the transfer of erythrocytes into the plasma of other blood. The technique of the erythrocyte sedimentation reaction. Non-coagulable blood (for example, in hemophiliacs, in the experiment after injections of heparin) can be studied directly by drawing blood into a glass tube, as narrow and high as possible, so that on the one hand less blood is used, and on the other, the difference in the rate of fall of erythrocytes in individual cases is more pronounced; after a certain period of time, usually after an hour, the height of the settled plasma column is noted. Under ordinary conditions, the addition of substances that prevent coagulation to the blood is required; with hirudin, in view of the difficulty of obtaining it, only occasional control observations have been made; in most cases, citric, oxalic, or fluorine salts are used, adding them to the blood either in substance or more often in the form of isotonic solutions to the blood (attempts to perform erythrocyte sedimentation reactions with native blood in paraffin-coated tubes have not become widespread). The erythrocyte sedimentation reaction is performed by taking blood from a vein (if possible without stagnation due to the retarding effect of stasis on sedimentation) or from a finger—micro-methods. The classic method is that of Westergren and Linzenmeier. In the USSR, the Panchenkov method is most commonly used. According to Westergren, first a 3.8% solution of sodium citrate is drawn into a 2-gram record syringe to the 0.4 mark, then the cubital vein is punctured and blood is drawn up to the 2.0 mark (1 part citrate to 4 parts blood); the blood is mixed in the syringe by careful tilting, it is poured into a test tube, and it is drawn into a pipette with an internal diameter of 2.5 mm to a height of 200 mm; the pipette is placed vertically in a stand with a plug at the bottom and a spring at the top. The height of the plasma column is read after 1 and 2 hours (with rapid sedimentation also after 1/2 hour). Normal figures for an hour, according to Westergren, are 1-3 mm for men and 4-7 mm for women (according to other authors, figures up to 10 mm with this technique still lie within the normal range). The Linzenmeier method differs in that a 5% solution of citrate is used, the vein is also punctured, then the citrated blood is poured into test tubes about 5 mm in diameter up to the upper mark corresponding to a blood volume of 1 cm³ (since the test tubes are not accurately calibrated, the height of the blood column will vary somewhat in individual test tubes, generally from 44 to 54 mm), and the test tubes are left suspended in a metal stand until the erythrocytes settle to the second mark, located exactly 18 mm below the first; the time in minutes is recorded during which the plasma settled exactly by the required height, which in the normal case requires 600 minutes for a man and 200-350 minutes for a woman, while in pathological cases of accelerated sedimentation correspondingly shorter periods of time are required. The method is inconvenient in that it requires a very large expenditure of time. Micro-methods, in which a smaller amount of blood is taken from the pulp of the finger, were proposed by Fåhræus and many subsequent authors, but were rejected as not sufficiently accurate. Of the micro-methods, the Balakhovsky method (the capillary is rinsed with 5% potassium oxalate, then blood is drawn into it and placed in a stand) and the Panchenkov method have become most widespread: a capillary graduated in millimeters is washed with citrate, then the same solution is drawn into the capillary to the 50 mark, blown out into a watch glass, then blood is drawn from the finger into the capillary to the 100 mark, i.e., to 100 mm, and blown out into the same watch glass; the blood-taking procedure is performed a second time, the blood is thoroughly mixed in the watch glass with citrate; thus a usual dilution of 1:4 is produced, then the citrated blood is drawn back into the capillary to the 100 mark and left standing in a relatively simple stand for 1 hour. Other simplifications, techniques, come down to working without special equipment; sedimentation is observed in the tuberculin syringe itself or in the Salé hemometer tube. To accelerate sedimentation and to obtain a faster reading of the reaction, it was proposed to place pipettes at an angle and centrifuge citrated blood tubes under certain conditions, or to add viscous colloids [gum (Kaufmann)]. More important than establishing new variants of individual technical details is the clarification of errors common to all methods and the possibility of comparing results obtained with the different existing methods for determining the erythrocyte sedimentation reaction. The addition of an anticoagulant to the blood both in substance and in the form of isotonic solutions changes the ratio of plasma to formed elements: in the first case (Bonninger's, Herrmann's method), the osmotic pressure of the plasma increases, which leads to wrinkling of the erythrocytes and consequently to a shift in the normal ratios between the erythrocyte mass and plasma in favor of the latter; on the other hand, the addition of citrate in an isotonic solution at different volume percentages of plasma in the blood of different subjects differently changes the initial concentration of blood protein bodies, which may play a decisive role in the reaction. Thus, with a normal content in the blood of about 50% plasma, it is diluted in the usual setting of the reaction in the ratio 2:1, in anemias, for example, with 75% plasma, in the original whole blood the plasma is diluted in setting the reaction in the ratio 3:1; finally, with a content of 25% plasma in the blood, it is diluted in the ratio 1:1; it is clear that due to the different actual dilution in extreme examples, the effect of protein bodies on the rate of sedimentation will be significantly distorted compared to their effect in native plasma. In addition, the same uneven dilution of formed elements causes more rapid sedimentation of oligocythemic blood, since the same erythrocytes in the same medium settle at different rates depending on the density of their suspension. The above makes it necessary when determining the rate of erythrocyte sedimentation to correct for the number of erythrocytes or the hematocrit value for the given blood, or instead of the hematocrit value, to note the maximum sedimentation in 24 hours and compare it with the amount of sedimentation in 1 hour; proposals in this direction have been made by individual authors, but they have not received general acceptance. Compared with the mentioned correction, the correction for the temperature at which the reaction was set has no practical significance. Below is a comparative table of sedimentation rates by various methods (according to Westergren and Panchenkov). Height of the plasma column in mm after 1 hour Time of sedimentation in min. to the 18-mm mark i according to Panchenkov according to Westergren (according to Linzenmeier) 700-800 400-450 300-350 225-275 7-8 10 12 175-225 150-175 115-135 10-15 20 30 85-100 60-70 15-25 40 50 45-50 35 25-40 40 and more 10 - Determination of the reaction in the form of a curve by reading the height of the plasma column through repeated, shorter time intervals, used by some authors, does not significantly clarify the reaction except in cases of very rapid sedimentation, where maximum figures are obtained already after a few minutes and where it is more advantageous and for the usual determination according to Westergren and Panchenkov to note sedimentation already after 15 and 30 min. * Physiological fluctuations of erythrocyte sedimentation. In women, erythrocyte sedimentation occurs more rapidly than in men. This is explained by the smaller number of erythrocytes in female blood, and the greater content of globulins and fibrinogen. During amenorrhea, erythrocyte sedimentation becomes slower, approaching the male norm. A slight acceleration is observed during the menstrual period. The acceleration of erythrocyte sedimentation during pregnancy, found by Fåhræus, has been confirmed by many subsequent researchers, however, a more significant acceleration is observed only from the 4th-5th month and therefore has no value for the early diagnosis of pregnancy (the acceleration is explained by the increased content of globulins and cholesterol in the blood and a decrease in Ca). Sedimentation in umbilical cord blood is very slowed down¹; also in newborns in the first days and hours, very low figures of erythrocyte sedimentation are noted (due to the small content of proteins in general and globulins in particular in the blood, as well as hypcholesterolemia, hypoglobulinemia, and acidosis). At the age of 2-6 months, erythrocyte sedimentation is faster than in adults; later it slows down again. During agony, a slowing of erythrocyte sedimentation has been noted (due to a decrease in globulins and proteins in general in the blood). Digestion can cause a slight acceleration of erythrocyte sedimentation.

Bolakhovsky observed strong fluctuations of erythrocyte sedimentation 1-2 hours after milk intake, which he attributes to reflex phenomena. Significant acceleration of erythrocyte sedimentation (Ruf) was observed by himself in experiments on dogs with a dry diet, while Gille (Hille) observed it during 24-hour fasting (along with an increase in fibrinogen and globulin due to the breakdown of the corresponding tissue protein). Fluctuations are observed throughout the day; in the evening, erythrocyte sedimentation may be somewhat accelerated (similar to evening increases in temperature). It is difficult to establish the exact boundary of pathological changes; one has to speak of a borderline zone, which usually indicates pathology, but with individual non-series determinations, it can also be encountered in a healthy individual. Erythrocyte sedimentation in pathological conditions. In pathology, erythrocyte sedimentation has been studied in the most diverse disease forms. In the following presentation, only typical⁵ examples will be given, and for many departments of pathology, only guiding principles. Among infectious diseases, the most typical changes, moreover confirmed on a huge material and having universally recognized practical value, are observed in tuberculosis_rc, especially tuberculosis of the lungs. The degree of acceleration of erythrocyte sedimentation in active tuberculosis, studied mainly by Westergren, depends on the degree of breakdown of lung tissue and therefore varies with different pathological-anatomical character of the process and usually also corresponds to the degree of decompensation of the process according to clinical assessment. Indurative processes give slight acceleration, productive processes give medium acceleration, and exudative processes give the greatest accelerations of erythrocyte sedimentation. Clinical assessment in terms of compensated, sub- and decompensated states even more coincides with the indications of the erythrocyte sedimentation reaction: decompensated cases give the highest, compensated cases the lowest figures of erythrocyte sedimentation. In relation to complications of tuberculosis_rc, both from the side of the lungs and from other organs, the following regularities can be noted. In cavities, it is not so much their presence and size, but the character of the main process and the progressive breakdown of lung tissue that determine the magnitude of erythrocyte sedimentation. It is not so much the presence and amount of sputum per se that determine the acceleration of erythrocyte sedimentation, but the character of the pulmonary process; with large isolated cavities that do not allow absorption, the excretion of large amounts of sputum can occur with normal erythrocyte sedimentation; even open processes under these 6S1 conditions may not give acceleration of erythrocyte sedimentation. Hemoptysis can give a temporary acceleration of erythrocyte sedimentation due to absorption of blood or a longer one due to a flare-up of the pulmonary process. Acute exudative pleuritis sharply accelerates erythrocyte sedimentation; this acceleration of erythrocyte sedimentation is particularly prolonged in specific tuberculous pleuritis. In encapsulated exudates, depending on the degree of their absorption, erythrocyte sedimentation may be slightly elevated up to normal figures. Dry pleuritis accelerates erythrocyte sedimentation. Such complications of pulmonary tuberculosis as anemia, nephroses, mixed infection significantly accelerate erythrocyte sedimentation. On the contrary, general amyloidosis or severe terminal cachexia can slow down erythrocyte sedimentation up to normal figures. Compared to other symptoms of tuberculous intoxication, erythrocyte sedimentation is often a more sensitive indicator of the intensity of pathological processes. Thus, changing in general parallel to fluctuations in weight and temperature, erythrocyte sedimentation often gives indications of the activity of the process where weight and temperature remain unchanged. Therefore, the diagnostic value of erythrocyte sedimentation in terms of determining the degree of compensation of the process is great; repeated determinations of erythrocyte sedimentation in the same patient are especially valuable for excluding偶然 large deviations and especially for judging the course of the process. Slight accelerations, especially with a single examination, may be observed in neurasthenia, thyrotoxicosis, in asthenics regardless of tuberculous infection. On the other hand, normal figures of erythrocyte sedimentation do not completely exclude the activity of the process (as was mistakenly believed in the first period after the discovery of the reaction). With these limitations, the determination of erythrocyte sedimentation in tuberculosis should be recognized as having great diagnostic value. To clarify the diagnosis of tuberculous process in doubtful cases, Grafe and Reinwein propose to enhance the reaction by subcutaneous injections of small doses of tuberculin 0.03-0.1 mg; acceleration of erythrocyte sedimentation by more than 3-4 mm according to these authors indicates the presence of a tuberculous process requiring treatment. Many works have been done with comparative determination of the erythrocyte sedimentation reaction and other biological indicators of the strength of infection and the state of immunity. With fluctuations in the leukocyte formula, erythrocyte sedimentation usually changes in parallel, i.e., acceleration corresponds to neutrophilic leukocytosis and eosinophilia; sometimes, however, the leukocyte formula appears to be a more precise indicator of the severity of the process. In tuberculosis, erythrocyte sedimentation changes in accordance with fluctuations in the albumin-globulin coefficient and in accordance with other serum reactions based on the lability of blood proteins, such as: Daranyi's reaction (flocculation with CaCl), reactions of Frisch and Starlinger, Matefi's reaction (flocculation with Al₂(SO₄)₃). The erythrocyte sedimentation reaction is considered more indicative of the activity of tuberculosis than the novocaine reaction of Costa, the reaction on labile globulin according to Leendertz, and the complement deviation reaction (Abramova). The urochromogenic reaction in urine and the diazo reaction are often positive in tuberculosis already with a significant increase in erythrocyte sedimentation. In addition to diagnostic value, the erythrocyte sedimentation reaction in tuberculosis has great prognostic value, since high figures of erythrocyte sedimentation give an unfavorable prognosis. The erythrocyte sedimentation reaction is of great importance for controlling treatment, being an indicator of worsening, improvement or stationarity of the process. Chemotherapeutic interventions can give an initial reactive acceleration, later replaced by a slowing of erythrocyte sedimentation in case of a favorable therapeutic effect; injection of tuberculin also causes initial acceleration (acceleration for the first 24 hours-up to 4 days after injection) as a manifestation of the focal reaction. The imposition of pneumothorax also gives a transient acceleration of the erythrocyte sedimentation reaction; later, a very indicative of treatment with pneumothorax slowing of erythrocyte sedimentation occurs. However, for the slowing of erythrocyte sedimentation during pneumothorax treatment, the factor of slowing of erythrocyte sedimentation due to the often developing erythrocytosis as such should always be taken into account. In sanatorium treatment, in addition to the great importance of the erythrocyte sedimentation reaction for selecting patients requiring sanatorium treatment, erythrocyte sedimentation is a good control of the results achieved. For childhood tuberculosis and processes in lymph glands, what has been said about pulmonary tuberculosis in adults essentially holds true, with the limitation that due to greater physiological fluctuations and greater variability of manifestations of immunological reactions, erythrocyte sedimentation in children changes less regularly; alongside great proponents of the erythrocyte sedimentation reaction for childhood material, there are authors who attribute very little importance to this reaction for childhood tuberculosis. For the differential diagnosis of pulmonary tuberculosis from other diseases of the respiratory tract, the erythrocyte sedimentation reaction can only be applied indirectly on the basis of confirmation by other purely clinical symptoms; thus, non-tuberculous pneumonias and pleuritis usually give a faster disappearing acceleration of erythrocyte sedimentation, and it has a more regular cyclic character in these processes (therefore, the curve of erythrocyte sedimentation over a certain period has predominant importance). Bronchitis in the absence of very large secretions give normal figures of erythrocyte sedimentation; also bronchiectasis in the absence of inflammatory perifocal processes. Emphysema and bronchial asthma do not give acceleration. From the example of the fluctuations of erythrocyte sedimentation in the best studied tuberculous infection, the complexity of the fluctuations of erythrocyte sedimentation and the difficulty of clinical assessment of this reaction are visible. In other infections, most of the mentioned factors also have significance-changes in the protein mirror of the blood, especially increase or decrease in fibrinogen (hyperinosis and hypinosis) in the blood, which regularly fluctuate in various infections, the degree of tissue breakdown, accidental complications of the main infection, accelerating (e.g., nephroses, anemias) or more rarely slowing down erythrocyte sedimentation (thickening of the blood, acidosis, agony). Factors slowing down erythrocyte sedimentation in infections include anaphylactic shock, which, along with other gross violations of the normal physico-chemical and morphological status of the blood, causes a fall in fibrinogen and almost complete cessation of erythrocyte sedimentation, later replaced by a phase of acceleration. Body immunization processes (due to increased breakdown of proteins of organs in the process of antibody formation) can also go with acceleration of erythrocyte sedimentation (e.g., vaccination against typhoid fever). Taking into account all the above factors, as well as knowing the empirically established range of fluctuations of the erythrocyte sedimentation reaction in individual infections, this reaction allows making valuable diagnostic and prognostic conclusions. In experimental infections, the beginning of acceleration of erythrocyte sedimentation has been established not with the first rise in temperature, but delayed by several hours up to a whole day.

For typhoid fever, which generally proceeds with cachexia, such a delay in the appearance of acceleration can extend throughout the first week; this can have differential diagnostic value in distinguishing typhoid, for example, from septic infection. On the 3rd week of typhoid fever, maximum acceleration is observed, slowly returning to normal with recovery. - In such acute infections as erysipelas or scarlet fever, erythrocyte sedimentation regularly and sharply increases; the clinical value of the reaction lies in the importance of early recognition of complications, in which erythrocyte sedimentation does not return to normal or gives new surges. In many chronic infections, the erythrocyte sedimentation reaction has been systematically studied, but it hardly has even approximately the same practical significance as in tuberculosis. In epidemic encephalitis, prolonged acceleration of erythrocyte sedimentation confirms the chronicity of the infection. In syphilis, florid cases give significant acceleration of erythrocyte sedimentation, while tertiary syphilis gives less; however, in specific arthritides, as in general in rheumatoid processes, relatively large values of the erythrocyte sedimentation reaction are common. Specific treatment slows down erythrocyte sedimentation, especially in children. The Wassermann and Sachs-Georgi reactions return to normal earlier than the erythrocyte sedimentation reaction. The administration of mercury preparations itself accelerates erythrocyte sedimentation, while salvarsan only does so in the presence of side effects. In malaria, acceleration of erythrocyte sedimentation is observed in the acute stage, after an attack - temporary relative slowing; quinine therapy brings erythrocyte sedimentation to normal, being an indicator of successful treatment (Lyakhovetsky and Maslova). According to Mayer, the acceleration in malaria can be partly explained by the increase in the specific weight of eryrythrocytes due to the load of malarial pigment. In surgical infections, there is also a regular large acceleration of erythrocyte sedimentation. After surgical trauma, acceleration occurs in connection with the absorption of tissue breakdown products due to a kind of protein therapy. On the other hand, severe purulent processes that cause anergy of the body, such as fatal perforative peritonitis, as an exception, can give a normal erythrocyte sedimentation reaction. For the early diagnosis of surgical diseases, the erythrocyte sedimentation reaction also does not have exclusive significance, since for example in acute appendicitis acceleration does not occur earlier than after 30 hours. Tissue breakdown without obvious infection occurs to a large extent in malignant tumors - this is why acceleration of the erythrocyte sedimentation reaction has diagnostic significance in them. Rubin found regular acceleration in carcinoma, however only with a significant tumor and with extensive breakdown; therefore, sclerotic forms of cancer can occur with normal erythrocyte sedimentation. In a controversial diagnosis between ulcer and stomach cancer, high figures of erythrocyte sedimentation speak for the neoplasm. - Diseases of metabolism with the character of increased tissue breakdown, such as severe diabetes, give acceleration of erythrocyte sedimentation parallel to the strength of intoxication, as well as experimental diabetes. - Increased metabolism in hyperthyroidism is also accompanied by regular acceleration of erythrocyte sedimentation, returning to normal under the influence of successful treatment. In myxedema, acceleration of erythrocyte sedimentation is not observed. Diseases of the joints often give significant acceleration of erythrocyte sedimentation in the presence of certain humoral changes (increase in fibrinogen), characteristic of auxiliary joint diseases (rheumatic polyarthritis, gonorrheal, tuberculous, syphilitic arthritides). In gouty arthritides, erythrocyte sedimentation is accelerated only during acute attacks; endocrine arthropathies and deforming osteoarthroses more often occur with normal erythrocyte sedimentation. Acceleration of erythrocyte sedimentation also allows distinguishing spondylitis from spondylosis. In balneological (or combined with medicinal) treatment of diseases of the motor organs, the erythrocyte sedimentation reaction allows monitoring the results of treatment (Brusilovsky). - In kidney diseases, only recently have regular fluctuations in erythrocyte sedimentation been noted. Mild subsiding nephritides can occur with normal erythrocyte sedimentation, while pronounced nephroses give extremely sharp acceleration of erythrocyte sedimentation, approximately parallel to the increase in blood cholesterol; on the other hand, uremic states also give significant acceleration of erythrocyte sedimentation (Tareev). Acceleration of erythrocyte sedimentation in some forms of Bright's disease may also depend on the presence of focal infection. Acceleration of erythrocyte sedimentation in anemias depends less on changes in proteins and other plasma components than on the number and properties of the erythrocytes themselves. First of all, the dilution of the erythrocyte suspension present in anemias significantly accelerates erythrocyte sedimentation. Macrocytes are located in the lower layers during sedimentation (and centrifugation) due to their greater specific weight. Therefore, erythrocytes of a patient with pernicious anemia, washed in physiological solution or suspended in Gower's fluid, sediment faster than the blood corpuscles in secondary hypochromic anemias. With marked anisocytosis, the upper boundary of the sedimenting erythrocytes appears indistinct due to the different sedimentation rates of individual erythrocytes. - In erythremias, in contrast to anemia, there can be marked slowing of erythrocyte sedimentation, down to 2-5 mm in a whole day (Westergren). Symptomatic erythrocytoses differ in less inhibition of erythrocyte sedimentation. Hemolytic anemias (in contrast to mechanical jaundices) give acceleration of erythrocyte sedimentation, partly due to the characteristic spherical shape of red blood cells in these diseases (which fall faster than normal). - In leukemias, acceleration of erythrocyte sedimentation is usually observed. In some other internal diseases, factors inhibiting erythrocyte sedimentation are of great importance, for example in liver diseases, circulatory disorders. In so-called catarrhal jaundices (of the 'hepatosis' type of Wichert) and generally in parenchymal liver lesions, slowing of erythrocyte sedimentation is typical due to the presence of bile acids in the blood (in severe liver insufficiency, this slowing may also depend on the reduced fibrinogen content in the blood). In other liver diseases, acceleration according to the general rules for inflammatory processes (cholecystitis, abscesses), in tumors, in breakdown of liver tissue (atrophy of the liver) can be observed. Acceleration of erythrocyte sedimentation after a milk load was attempted to be used as a functional test for liver insufficiency according to the principle of the Vidal crisis; this reaction has no practical significance. - In heart insufficiency, slowing of erythrocyte sedimentation is usually observed [due to accumulation of CO₂, erythrocytosis ]. In compensated defects, acceleration can be a manifestation of active infection - endocarditis, which can have diagnostic significance. Accelerations of erythrocyte sedimentation can also be due to congestive bronchitis, bronchopneumonia, arteriosclerosis (cholesterolemia), in syphilitic aortitis, in essential hypertension in the case of development of renal insufficiency. Cyanoses of non-circulatory origin also slow down erythrocyte sedimentation (tracheal stenosis, also in experiment). - Slowing of erythrocyte sedimentation can also be observed in neurotics, hysterics, in allergic conditions, in organic diseases of the vegetative centers. As for other branches of medicine, the practical significance of the erythrocyte sedimentation reaction in each of them is based on the principles discussed above. - In micropediatrics, the factors limiting the significance of the reaction are the lability of the blood plasma of infants, the instability of acid-base equilibrium, and the significant influence of nutritional factors. Nevertheless, a large number of works attempts to find practically important regularities in childhood pathology. - In neuropathology and psychiatry, in such diseases as progressive paralysis, tabes, syphilis of the brain, acceleration is observed parallel to the degree of inflammatory changes; purely degenerative diseases as a rule do not give acceleration of erythrocyte sedimentation. In schizophrenia, different groups of patients react differently. Acute meningitides, encephalitides give sharp acceleration, brain tumors - depending on the degree of breakdown; epilepsy - does not give acceleration of erythrocyte sedimentation. - In ophthalmology and otorhinolaryngology, the significance of erythrocyte sedimentation is very small.

E. Tareev. Erythrocyte sedimentation in obstetrics and in gynecological diseases. The wide application of the erythrocyte sedimentation reaction in gynecology and obstetrics depends not on any particularly favorable conditions for the value of this reaction in the indicated field, but rather on historical continuity. The duration of erythrocyte sedimentation in healthy mature women averages 3-4 hours (Lincenmeyer), with fluctuations ranging from 2_1/2 to 6 (and even more) hours. The ovarian-menstrual cycle very insignificantly changes erythrocyte sedimentation in the direction of some acceleration. During pregnancy, mainly in the second half, erythrocyte sedimentation is significantly accelerated. Acceleration of erythrocyte sedimentation allows one to distinguish pregnancy in the second half from uterine myoma. In obstetric practice, the erythrocyte sedimentation reaction has little significance: the reaction is clearly accelerated at a time in pregnancy when the diagnosis can be established on the basis of a number of other signs; in the early stages of pregnancy, the erythrocyte sedimentation reaction is accelerated only slightly. In cases of uterine pregnancy (not infected), erythrocyte sedimentation is accelerated (from ³/₄ to 1^1/2 hours); in cases of ectopic pregnancy with abundant hemorrhage into the abdominal cavity, erythrocyte sedimentation can be significantly accelerated, reaching even 10 minutes. However, the clinical picture of the disease in ectopic pregnancy undoubtedly has much more decisive importance than the erythrocyte sedimentation reaction, since it can be accelerated in inflammatory processes of the female genital sphere not accompanied by an increase in temperature. In the presence of haematocele retrouterinum or haematocele peritubarium, subsequent acceleration of the erythrocyte sedimentation reaction indicates the addition of infection. In abortions, acceleration indicates complications—adnexitis, etc. In acute adnexitis, acceleration is more pronounced, in chronic adnexitis, acceleration is less pronounced. Toxicoses of pregnancy have varying effects on erythrocyte sedimentation: eclampsia often slows down erythrocyte sedimentation. In gynecological diseases, the erythrocyte sedimentation reaction is applied very frequently. The distinction between new growths and inflammatory processes is hardly possible on the basis of erythrocyte sedimentation data. Benign new growths of the sexual organs in general do not change the speed of erythrocyte sedimentation, unless they are accompanied by chronic hemorrhages that change the blood composition. In benign tumors, erythrocyte sedimentation can accelerate only with the appearance of this or that degenerative changes, malignant degeneration or due to impaired nutrition (e.g., necrosis) on the basis of twisting of the tumor stalk or strangulation of the latter. In malignant new growths, erythrocyte sedimentation is subject to very significant fluctuations. In meno- or metrorrhagias not depending on the presence of new growths (metropathia haemorrhagica, adenomyosis, endometritis glandularis, etc.), erythrocyte sedimentation is somewhat accelerated. In inflammations of the sexual organs (vagina, cervix or uterine cavity), when the discharge has free outflow, erythrocyte sedimentation is not accelerated at all or is accelerated only slightly. The greatest acceleration of the erythrocyte sedimentation reaction is reached in inflammation of the tubes, ovaries, pelvic cellular tissue and peritoneum. 687

ERYTHROCYTE SEDIMENTATION. The erythrocyte sedimentation reaction acquires special value in diagnostic respect not in the acute stage of inflammation, when the clinical picture is clear, but in subacute and especially in chronic cases. In this respect, the erythrocyte sedimentation reaction has taken a firm place in gynecological diseases as a diagnostic method that often possesses greater sensitivity than the determination of the total number of leukocytes or the leukocyte formula. As a rule, erythrocyte sedimentation is accelerated when acute inflammatory phenomena have long subsided and temperature is normal. The erythrocyte sedimentation reaction facilitates the differential diagnosis between new growths and inflammatory tumors of the sexual organs. In chronic inflammation of the appendages, acceleration of erythrocyte sedimentation indicates the activity of the process. With a reaction duration of less than an hour, one must always think about the existence of a virulent infection; figures greater than 1^1/2 hours with great probability indicate the absence of active foci. The erythrocyte sedimentation reaction acquires special value in the choice of the method of therapy; a duration of erythrocyte sedimentation less than 1^1/2 hours makes operative intervention risky in the sense of the possibility of exacerbation of the inflammatory process; it is also risky to apply some conservative methods of treatment (e.g., muds, gynecological massage, etc.) if erythrocyte sedimentation is less than 1^1/2 hours. Significant acceleration of the erythrocyte sedimentation reaction (less than 1 hour) even in the absence of other objective signs of inflammation in the area of the sexual organs is sufficient reason to postpone operative intervention, if the latter is not dictated by vital indications, for example, malignant tumor, ectopic pregnancy, significant hemorrhage, twisting of the tumor stalk, etc.