Histology of the Blood, Normal and Pathological. Paul Ehrlich

pipette, very carefully cleaned, with cedar wood oil, and sucks up the blood, as it comes from the fingerprick into the filled pipette. The blood displaces the oil, and as it only comes into contact with perfectly smooth surfaces, it remains fluid. By means of a centrifugal machine, of which he has constructed a very convenient variation, the oil as the lighter body is completely removed from the blood; and the plasma is also separated from the corpuscles. Three sharply defined layers are then visible, the layer of oil above, the plasma layer, and the layer of the red blood corpuscles. In as much as the apparatus is calibrated, the relation between the volumes of the plasma and corpuscles can be read off. No microscopical alterations in the corpuscles are to be observed.

      Though this procedure seems very difficult of execution, it is nevertheless the only one, which has really advanced clinical pathology. The results of Kœppe—not as yet very numerous—give the total volume of the red corpuscles as 51.1–54.8%, an average of 52.6%.

      M. and L. Bleibtreu have endeavoured indirectly to ascertain the relation of the volume of the corpuscles to that of the plasma. Mixtures of blood with physiological saline solution in various proportions are made, in each the amount of nitrogen in the fluid which is left after the corpuscles have settled is estimated. With the aid of quantities so obtained they calculate mathematically the volume of the serum and corpuscles respectively. Apart from the fact that a dilution with salt solution is also here involved, this method is too complicated and requires amounts of blood too large for clinical purposes. Th. Pfeiffer has tried to introduce it clinically in suitable cases, but has not so far succeeded in obtaining definite results. That, however, the relations between the relative volume of the red corpuscles and quantity of hæmoglobin are by no means constant, is well shewn by conditions (for example the acute anæmias) in which an "acute swelling" of the individual red discs occurs (M. Herz), but without a corresponding increase in hæmoglobin. The same conclusion results from recent observations of v. Limbeck, that in catarrhal jaundice a considerable increase of volume of the red blood corpuscles comes to pass under the influence of the salts of the bile acids.

      As we have several times insisted, the quantity of hæmoglobin affords the most important measure of the severity of an anæmic condition. Those methods which neither directly nor indirectly give an indication of the amount of hæmoglobin are only so far of interest that they possibly afford an elucidation of the special pathogenesis of blood diseases in particular cases. To these belong the estimation of the alkalinity of the blood, which in spite of extended observations has not yet obtained importance in the pathology of the blood.

      A value to which perhaps attention will be more directed than it has up to the present time by clinicians is the rate of coagulation of the blood, for which comparative results may be obtained by Wright's handy apparatus, the "Coagulometer." In certain conditions, particularly in acute exanthemata, and in the various forms of the hæmorrhagic diathesis, the clotting time is distinctly increased, or indeed clotting may remain in abeyance. Occasionally a distinct acceleration in the clotting, compared with the normal, may be observed. Wright has further ascertained in his excellent researches, that the clotting time can be influenced by drugs: calcium chloride, carbonic acid raise, citric acid, alcohol and increased respiration diminish the clotting power of the blood.

      Recently Hayem has repeatedly called attention to a condition, that is probably closely connected with the coagulability of the blood. Although coagulation has set in, the separation of the serum from the clot occurs only very slightly or not at all. Hayem asserts, that he has found such blood in Purpura hæmorrhagica, Anæmia perniciosa protopathica, malarial cachexia: and some infectious diseases.

      For such observations large amounts of blood are needed, which are clinically not frequently available. Certain precautions must be observed, as has been ascertained in the preparation of diphtheria serum, so that the yield of serum may be the largest possible. Amongst these that the blood should be received in longish vessels, which must be especially carefully cleaned, and free from all traces of fat. If the blood-clot does not spontaneously retract it must be freed from the side of the glass with a flat instrument like a paper-knife without injuring it. If no clot occurs in the cold, a result may perhaps follow at blood temperature.

      In spite however of all artifices and all care, it is here and there, under pathological conditions, impossible to obtain even a trace of serum from considerable amounts of blood. In a horse for example which was immunised against diphtheria, and had before yielded an unusually large quantity of serum, Ehrlich was able to obtain from 22 kg. of blood scarcely 100 cc. serum, when the animal was bled on account of a tetanus infection.

      Perhaps a larger rôle is to be allotted in the diseases of the blood to these conditions. Hayem already turns the incomplete production of serum to account, for distinguishing protopathic pernicious anæmia from other severe anæmic conditions. A bad prognosis too may be made when for example in cachetic states this phenomenon is to be observed.

      A few methods still remain to be mentioned which test the resistance of the red blood corpuscles to external injuries of various kinds.

      Landois, Hamburger and v. Limbeck ascertain for instance the degree of concentration of a salt solution, in which the red corpuscles are preserved ("isotonic concentration," Hamburger) and those which cause an exit of the hæmoglobin from the stroma. The erythrocytes are the more resistant, the weaker the concentration which leaves them still uninjured.

      Laker tests the red blood corpuscles as regards their resistance to the electric discharge from a Leyden jar, and measures it by the number of discharges up to which the blood in question remains uninjured.

      Clinical observation has not yet gained much by these methods. So much only is certain, that in certain diseases: anæmia, hæmoglobinuria, and after many intoxications, the resistance, as measured by the methods above indicated, is considerably lowered.

      FOOTNOTES:

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      [1] For the estimation of the numbers of white corpuscles, relatively to the red, and of the different kinds relatively to each other, see the section on the morphology.

[2] In Roy's method, mixtures of glycerine and water are used. By means of a curved pipette, the drop of blood is brought into the fluid, and its immediate motion observed. Lazarus Barlow has modified this method. He employs mixtures of gum and water, and instead of several tubes, one only; and into this the mixtures are introduced, those of higher specific gravity being naturally at the bottom. The alternate layers are coloured, and remain distinguishable for several hours.

[3] In conditions of shock experimentally produced, the specific gravity of the total blood is increased, that of the plasma, however, is diminished (Roy and Cobbett).

THE MORPHOLOGY OF THE BLOOD.

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A. METHODS OF INVESTIGATION.

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      A glance at the history of the microscopy of the blood shews that it falls into two periods. In the first, which is especially distinguished by the work of Virchow and Max Schultze, a quantity of positive knowledge was quickly won, and the different forms of anæmia were recognised. But close upon this followed a standstill, which lasted for some decades, the cause of which lay in the circumstance that observers confined themselves to the examination of fresh blood. What in fact was to be seen with the aid of this simple method, these distinguished observers had quickly exhausted. That these methods were inadequate is best shewn