Chapter 8

VII. BLOOD PARASITES

A study of blood bacteriology is useful, but is hardly practicable for the practitioner. Most bacteria can be detected only by culture methods. Thespirillum of relapsing fevercan be identified by the method for the malarial parasite in fresh blood. The blood must be taken during a paroxysm. The organism is an actively motile spiral thread, about four times the diameter of a red corpuscle in length. The movements which its active motion causes among the corpuscles render it conspicuous. It can also be seen in stained preparations (Fig. 78). The disease has rarely been seen in the United States.

Of the numerous animal parasites which have beenfound in the blood, three are especially interesting clinically:Plasmodium malariæ,Filaria sanguinis hominis, andTrypanosoma hominis.

1.Plasmodium Malariæ.—This organism is one of a large group, thehemosporidia(p. 247), many of which live within and destroy the red corpuscles of various animals. Three varieties are associated with malarial fever in man—the tertian, quartan, and estivo-autumnal malarial parasites.

(1)Life Histories.—There are two cycles of development: one, theasexual, in the blood of man; and the other, thesexual, in the intestinal tract of a particular variety of mosquito.

(a)Asexual Cycle.—The young organism enters the blood through the bite of the mosquito. It makes its way into a red corpuscle, where it appears as a small, pale "hyaline" body. This body exhibits ameboid movement and increases in size. Soon, dark-brown granules derived from the hemoglobin of the corpuscle make their appearance within it. When it has reached its full size—filling and distending the corpuscle in the case of the tertian parasite, smaller in the others—the pigment-granules gather at the center or at one side; the organism divides into a number of small hyaline bodies, the spores or merozoites; and the red corpuscle bursts, setting spores and pigment free in the blood-plasma. This is called segmentation. It coincides with, and by liberation of toxins causes, the paroxysm of the disease. A considerable number of the spores are destroyed by leukocytes or other agencies; the remainder enter other corpuscles and repeat the cycle. Many of the pigment-granules are taken up by leukocytes. In estivo-autumnal fever segmentation occurs in theinternal organs and the segmenting and larger pigmented forms are not seen in the peripheral blood.

The asexual cycle of the tertian organism occupies forty-eight hours; of the quartan, seventy-two hours; of the estivo-autumnal, an indefinite time—usually twenty-four to forty-eight hours.

The parasites are thus present in the blood in great groups, all the individuals of which reach maturity and segment at approximately the same time. This explains the regular recurrence of the paroxysms at intervals corresponding to the time occupied by the asexual cycle of the parasite. Not infrequently there is multiple infection, one group reaching maturity while the others are still young; but the presence of two groups which segment upon the same day is extremely rare. Fevers of longer intervals—six, eight, ten days—are probably due to the ability of the body, sometimes of itself, sometimes by aid of quinin, to resist the parasites so that a number sufficient to cause a paroxysm do not accumulate in the blood until after several repetitions of the asexual cycle. In estivo-autumnal fever the regular grouping, while usually present at first, is soon lost, thus causing "irregular malaria."

(b)Sexual Cycle.—Besides the ameboid individuals which pass through the asexual cycle, there are present with them in the blood many individuals with sexual properties. These are calledgametes. They do not undergo segmentation. Many of them are apparently extracellular, but stained preparations usually show them to be surrounded by the remains of a corpuscle. In tertian and quartan malaria they cannot easily be distinguished from the asexual individuals until a variable time after the blood leaves the body, when the male gamete sends outone or more flagella. In estivo-autumnal malaria the gametes take distinctive ovoid and crescentic forms, and are not difficult to recognize. They are very resistent to quinin and often persist in the blood long after the ameboid forms have been destroyed, but are probably incapable of continuing the disease until they have passed through the cycle in the mosquito.

When a malarious person is bitten by a mosquito, the gametes are taken with the blood into its stomach. Here a flagellum from the male unites with the female, which soon thereafter becomes encysted in the wall of the intestine. After a time it ruptures, liberating many minute rods, or sporozoites, which have formed within it. These migrate to the salivary glands, and are carried into the blood of the person whom the mosquito bites. Here they enter red corpuscles as young malarial parasites, and the majority pass through the asexual cycle just described.

The sexual cycle can take place only within the body of one genus of mosquito,anopheles. Absence of this mosquito from certain districts explains the absence ofmalaria. It is distinguished from our common house-mosquito,culex, by the relative lengths of proboscis and palpi (Fig. 79), which can be seen with a hand-lens, by its attitude when resting, and by its dappled wing (Fig. 80). Anopheles is strictly nocturnal in its habits; it usually flies low, and rarely travels more than a few hundred yards from its breeding-place, although it may be carried by winds. These facts explain certain peculiarities in malarial infection; thus, infection occurs practically only at night; it is most common near stagnant water, especially upon the side toward which the prevailing winds blow; and thedanger is greater when persons sleep upon or near the ground than in upper stories of buildings. The insects frequently hibernate in warmed houses, and may bite during the winter. A mosquito becomes dangerous in eight to fourteen days after it bites a malarious person, and remains so throughout its life.

(2)Detection.—Search for the malarial parasite may be made in either fresh blood or stained films. If possible, the blood should be obtained a few hours before the chill—never during it nor within a few hours afterward, since at that time (in single infections) only the very young, unpigmented forms are present, and these are the most difficult to find and recognize. Sometimes many parasites are found in a microscopic field; sometimes, especially in estivo-autumnal infection, owing to accumulation in internal organs, careful search is required to find any, despite very severe symptoms. Quinin causes them rapidly to disappear from the peripheral blood, and few or none may be found after its administration. In the absence of organisms, the presence of pigment granules within leukocytes—polymorphonuclears and large mononuclears—may be taken as presumptive evidence of malaria. Pigmented leukocytes (Plate VI) are most numerous after a paroxysm.

(a)In Fresh Unstained Blood(Plate VII).—Obtain a small drop of blood from the finger or lobe of the ear. Touch the center of a cover-glass to the top of the drop and quickly place it, blood side down, upon a slide. If the slide and cover be perfectly clean and the drop not too large, the blood will spread out so as to present only one layer of corpuscles. Search with a one-twelfth-inch objective, using very subdued light.

The young organisms appear as small, round, ring-like or irregular, colorless bodies within red corpuscles. The light spots caused by crenation and other changes in the corpuscles are frequently mistaken for them, but are generally more refractive or have more sharply defined edges. The older forms are larger colorless bodies containing granules of brown pigment. In the case of the tertian parasite, these granules have active vibratory motion, which renders them conspicuous; and as the parasite itself is very pale, one may see only a large pale corpuscle in which fine pigment-granules are dancing. Segmenting organisms, when typical, appear as rosets, often compared to daisies, the petals of which represent the segments, while the central brown portion represents the pigment. Tertian segmenting forms are less frequently typical than quartan. Flagellated forms are not seen until ten to twenty minutes after the blood has left the vessels. As Cabot suggests, one should, while searching, keep a sharp lookout for unusually large or pale corpuscles, and for anything which is brown or black, or in motion.

(b)In Stained Films(Plate VI).—Recognition of the parasite, especially the young forms, is much easier in films stained by Wright's or some similar stain than in fresh blood. When very scarce, they may sometimes be found, although their structure is not well shown, by the method of Ruge. This consists in spreading a very thick layer of blood, drying, placing for a few minutes in a fluid containing 5 per cent. formalin and 1 per cent. acetic acid, which removes the hemoglobin and fixes the smear, rinsing, drying, and finally staining. If Wright's stain be used in this method, it is recommended that thepreparation be subsequently stained for a half-minute with borax-methylene-blue (borax, 5; methylene-blue, 2; water, 100).

In films which are properly stained with Wright's fluid the young organisms are small, round, ring-like or irregular, sky-blue bodies, each with a very small, sharply defined, reddish-purple chromatin mass. Many structures—deposits of stain, dirt, blood-plaques lying upon red cells, etc.—may simulate them, but should not deceive one who looks carefully for both the blue cytoplasm and the reddish-purple chromatin. A plaque upon a red corpuscle is surrounded by a colorless zone rather than by a distinct blue body. Young estivo-autumnal parasites commonly take a "ring" form (the chromatin mass representing the jewel), which is infrequently assumed by the other varieties. The older tertian and quartan organisms show larger sky-blue bodies with more reticular chromatin, and contain brown granules of pigment, which, however, is less evident than in the living parasite. The chromatin is often scattered through the cytoplasm or apparently outside of it, and is sometimes difficult to see clearly. Typical "segmenters" present a ring of rounded segments or spores, each with a small, dot-like chromatin mass. With the tertian parasite, the segments more frequently form an irregular cluster. The pigment is collected near the center or scattered among the segments. In estivo-autumnal fever usually only the small "ring bodies" and the crescentic and ovoid gametes are seen in the blood. The gametes are easily recognized. Their length is somewhat greater than the diameter of a red corpuscle. Their chromatin is usually centrally placed, and they contain more or less coarse pigment. The remains of thered cell often form a narrow rim around them or fill the concavity of the crescent.

While the parasites are more easily found in stained preparations, the varieties are more easily differentiated in fresh blood. The chief distinguishing points are included in the following table:

2.Filaria Sanguinis Hominis.—Of the several varieties of this worm,Filaria nocturnais most common andmost important clinically. The adults are thread-like worms about 8 to 10 cm. long. They are rarely seen. They live in pairs in the lymphatic channels and glands, especially those of the pelvis and groin, and often occur in such numbers as to obstruct the flow of lymph. This is the most common cause of elephantiasis. Infection is very common in tropical countries, especially in Samoa, the West Indies, Central America, and the Isthmus of Panama. It is said that in Samoa 50 per cent. of the natives are infected.

The female is viviparous, and produces vast numbers of embryos, which appear in the circulating blood. These embryos are very actively motile, worm-like structures, about as wide as a red corpuscle and 0.2 to 0.4 mm. long (Fig. 107). They are found in the peripheral blood only at night, appearing about 8P.M.and reaching their maximum number—which is sometimes enormous—about midnight. If the patient change his time of sleeping, they will appear during the day. Infection is carried by a variety of mosquito, which acts as intermediate host.

Diagnosis rests upon detection of embryos in the blood. They can be seen in stained preparations, but are best found in fresh unstained blood. A rather large drop is taken upon a slide, covered, and examined with a low power. The embryo can be located by the commotion which its active motion produces among the corpuscles. This motion consists almost wholly in apparently purposeless lashing and coiling movements, and continues for many hours.

3.Trypanosoma Hominis.—Various trypanosomes are common in the blood of fishes, amphibians, birds, andmammals (Fig. 81). They live in the blood-plasma and do not attack the corpuscles. In some animals they are apparently harmless; in others they are an important cause of disease.

Trypanosoma hominisis an actively motile, spindle-shaped organism, two or three times the diameter of a red corpuscle in length, with one end terminating in a long flagellum. It can be seen with medium power objectives in either fresh or stained blood. Human trypanosomiasis is common in Africa. As a rule, it is a very chronic disease. "Sleeping sickness" is a late stage when the organisms have invaded the cerebrospinal fluid. Infection is carried by a biting fly,Glossina palpalis.

VIII. SERUM REACTIONS

1.Agglutination.—In the blood-serum of persons suffering from certain infectious diseases there exist soluble bodies, called agglutinins, which have the property ofrendering non-motile and clumping the specific micro-organism of the disease, and have little or no influence upon other bacteria. This "agglutination" takes place even when the blood is greatly diluted. Undiluted normal blood can agglutinate most bacteria, but loses this power when diluted to any considerable degree. These facts are taken advantage of in the diagnosis of several diseases.

When applied to the diagnosis of typhoid fever, the phenomenon is known as theWidal reaction. As yet, it is the only agglutination reaction which has any practical value for the practitioner.

Either blood-serum or the whole blood may be used. Serum is the better. To obtain it, it is convenient to use little vials, such as can be made by breaking off the lower half-inch of the tubes which have contained peptonizing powder. They must, of course, be well cleaned. One of these is filled to a depth of about one-fourth inch from a puncture in the finger, and is set aside for a few hours. When the clot has separated, it is picked out with a needle, leaving the serum. One drop of the serum is then added to nine drops of normal salt solution, making a dilution of 1:10. Distilled water may be used for dilution, but is more liable to cause error. The dilution can be more accurately made in the leukocyte pipet of the Thoma-Zeiss instrument. When the whole blood is used, it can be secured in the pipet and at once diluted with the salt solution. When it must be transported a considerable distance, dried blood is most convenient. A large drop is allowed to dry upon a clean slide or unglazed paper. It will keep for months without losing its agglutinating power. When ready to make the test, the dried stain is dissolved in ten drops of normal salt solution, care beingtaken that the drops are about the same size as the original drop of blood.

The reaction can be detected either microscopically or macroscopically:

Microscopic Method.—(1) The blood or serum having been obtained and diluted 1:10 as just described, mix it with a bouillon culture of the typhoid bacillus to any desired dilution. One drop of each makes a blood-dilution of 1:20, etc. The culture should be between eighteen and twenty-four hours old, and the bacilli must be actively motile. A stock agar culture should be kept at room temperature, and bouillon tubes inoculated the day before the examination is to be made. Agar cultures can be purchased from dealers in biologic products. They must be renewed monthly.

Instead of the bouillon culture, McFarland recommends the use of a suspension made by removing some of the growth from the surface of a fresh agar culture and mixing it well with a little sterile water. It is then necessary to examine the suspension microscopically to make sure that there are no natural clumps.

(2) Place a few drops of the mixture of blood and culture upon a perfectly clean slide and apply a cover-glass. The cover may be ringed with vaselin to prevent evaporation, but this is not usually necessary.

(3) Examine at intervals with a high dry lens—a one-sixth will answer very well. The light must be very subdued. At first the bacilli should be actively moving about. If the blood be from a case of typhoid, they will gradually lose their motion and gather together in clumps (Fig. 82). The clumps should be large, and the few bacilli remaining isolated should be motionless. Pseudo-reactions, in which there are a few small clumps of bacilli whose motion is not entirely lost, together with many freely moving bacilli scattered throughout the field, should not mislead. As a control, a dropof the culture should always be examined before making the test.

Normal blood may produce clumping if time enough be allowed. The diagnostic value of a positive reaction is, therefore, impaired unless clumping takes place within a limited time. With dilution of 1:20 the time limit should not exceed one-half hour; with 1:40, one hour. Tests based upon lower dilution than 1:20 are probably not reliable.

Macroscopic Method.—The principle is the same as that of the microscopic method. Clumping of the bacilli causes a flocculent precipitate, which can be seen with the naked eye. A dead culture gives the same results as a living one. This method is as reliable as the microscopic and is more convenient for the practitioner, although it requires more time.

Dead cultures, together with apparatus for diluting the blood, are put up at slight cost by various firms under the names of typhoid diagnosticum, typhoid agglutometer, etc. Full directions accompany these outfits.

The Widal reaction is positive in over 95 per cent. of all cases of typhoid fever. It may, rarely, be positive in other conditions, owing, sometimes at least, to faulty technic. It appears often as early as the sixth or seventh day; usually during the second week. It remains during the whole course of the disease, and frequently persists for years.

2.Opsonins.—That phagocytosis plays an important part in the body's resistance to bacterial invasion has long been recognized. According to Metchnikoff, this property of leukocytes resides entirely within themselves, depending upon their own vital activity. The recent studies of Wright and Douglas, upon the contrary, indicate that the leukocytes are impotent in themselves, and can ingest bacteria only in the presence of certain substances which exist in the blood-plasma. These substances have been namedopsonins. Their nature is undetermined. They probably act by uniting with the bacteria, thus preparing them for ingestion by the leukocytes; but they do not cause death of the bacteria, nor produce any appreciable morphologic change. They appear to be more or less specific, a separate opsonin being necessary for phagocytosis of each species of bacteria. There are, moreover, opsonins for other formed elements—red blood-corpuscles, for example. It has been shown that the quantity of opsonins in the blood can be greatly increased by inoculation with dead bacteria.

To measure the amount of any particular opsonin in the blood Wright has devised a method which involves many ingenious and delicate technical procedures. Much skill, such as is attained only after considerable training in laboratory technic, is requisite, and there are many sourcesof error. It is, therefore, beyond the province of this work to recount the method in detail. In a general way it consists in: (a) Preparing a mixture of equal parts of the patient's blood-serum, an emulsion of the specific micro-organism, and a suspension of washed leukocytes; (b) preparing a similar mixture, using serum of a normal person; (c) incubating both mixtures for a definite length of time; and (d) making smears from each, staining, and examining with a one-twelfth objective. The number of bacteria which have been taken up by a definite number of leukocytes is counted, and the average number of bacteria per leukocyte is calculated; this gives the "phagocytic index." The phagocytic index of the blood under investigation, divided by that of the normal blood, gives theopsonic indexof the former, the opsonic index of the normal blood being taken as 1. Simon regards the percentage of leukocytes which have ingested bacteria as a more accurate measurement of the amount of opsonins than the number of bacteria ingested, because the bacteria are apt to adhere and be taken in in clumps.

Wright and his followers regard the opsonic index as an index of the power of the body to combat bacterial invasion. They claim very great practical importance for it as an aid to diagnosis and as a guide to treatment by the vaccine method. This method of treatment consists in increasing the amount of protective substances in the blood by injections of normal-salt suspensions of dead bacteria of the same species as that which has caused and is maintaining the morbid process, these bacterial suspensions being called "vaccines." The opinion of the majority of conservative men seems to be that while vaccine therapy is undoubtedly an important addition to ourmethods of treatment of bacterial infections, particularly of those which are strictly local, yet the value of the opsonic index in measuring resisting power or as an aid to diagnosis and guide to treatment is stillsub judice.

IX. TESTS FOR RECOGNITION OF BLOOD

1.Guaiac Test.—The technic of this test has been given (p. 89). It may be applied directly to a suspected fluid, or, better, to the ethereal extract. Add a few cubic centimeters of glacial acetic acid to about 10 c.c. of the fluid; shake thoroughly with an equal volume of ether; decant, and apply the test to the ether. In case of dried stains upon cloth, wood, etc., dissolve the stain in distilled water and test the water, or press a piece of moist blotting-paper against the stain, and touch the paper with drops of the guaiac and the turpentine successively.

2.Teichmann's Test.—This depends upon the production of characteristic crystals ofhemin. It is a sensitive test, and, when positive, is absolute proof of the presence of blood. A number of substances—lime, finesand, iron rust—interfere with production of the crystals; hence negative results are not always conclusive. Dissolve the suspected stain in a few drops of normal salt solution upon a slide. If a liquid is to be tested, evaporate some of it upon a slide and dissolve the residue in a few drops of the salt solution. Let dry, apply a cover-glass, and run glacial acetic acid underneath it. Heatvery gentlyuntil bubbles begin to form, replacing the acid as it evaporates. Allow to cool slowly. When cool, replace the acid with water, and examine for hemin crystals with two-thirds and one-sixth objectives. The crystals are dark-brown rhombic plates lying singly or in crosses, and are easily recognized (Fig. 83). Failure to obtain them may be due to too great heat or too rapid cooling. If not obtained at first, let the slide stand in a warm place, as upon a hot-water radiator, for an hour.

X. SPECIAL BLOOD PATHOLOGY

The more conspicuous characteristics of the blood in various diseases have been mentioned in previous sections. Although the great majority of blood changes are secondary, there are a few blood conditions in which the changes are so prominent, or the etiology so obscure, that they are commonly regarded as blood diseases. These will receive brief consideration here.

A. ANEMIA

This is a deficiency of hemoglobin, or red corpuscles, or both. It is either primary or secondary. The distinction is based chiefly upon etiology, although each type presents a more or less distinctive blood-picture. Secondary anemia is that which is symptomatic of some otherpathologic condition. Primary anemia is that which progresses without apparent cause.

1.Secondary Anemia.—The more important conditions which produce secondary or symptomatic anemia are:

(a)Poor nutrition, which usually accompanies unsanitary conditions, poor and insufficient food, etc.

(b)Acute infectious diseases, especially rheumatism and typhoid fever. The anemia is more conspicuous during convalescence.

(c)Chronic infectious diseases:tuberculosis, malaria, syphilis, leprosy.

(d)Chronic exhausting diseases, as heart disease, chronic nephritis, cirrhosis of the liver, and gastro-intestinal diseases, especially when associated with atrophy of gastric and duodenal glands. The last may give an extreme anemia, indistinguishable from pernicious anemia.

(e)Chronic poisoning, as from lead, arsenic, and phosphorus.

(f)Hemorrhage—either repeated small hemorrhages, as from gastric cancer and ulcer, uterine fibroids, etc., or a single large one.

(g)Malignant tumors:these affect the blood partly through repeated small hemorrhages, partly through toxic products, and partly through interference with nutrition.

(h)Animal Parasites.—Some cause no appreciable change in the blood; others, like theUncinariaandBothriocephalus latus, may produce a very severe anemia, almost identical with pernicious anemia. Anemia in these cases is probably due both to toxins and to abstraction of blood.

The blood-picture varies with the grade of anemia.Diminution of hemoglobin is the most characteristic feature. In mild cases it is slight, and is the only blood change to be noted. In very severe cases hemoglobin may fall to 15 per cent. Red corpuscles are diminished in all but very mild cases, while in the severest cases the red corpuscle count is sometimes below 2,000,000. The color index is usually decreased.

Although the number of leukocytes bears no relation to the anemia, leukocytosis is common, being due to the same cause.

Stained films show no changes in very mild cases. In moderate cases variations in size and shape of the red cells and polychromatophilia occur. Very severe cases show the same changes to greater degree, with addition of basophilic degeneration and the presence of normoblasts in small or moderate numbers. Megaloblasts in very small numbers have been encountered in extremely severe cases. Blood-plaques are usually increased.

2.Primary Anemia.—The commonly described varieties of primary anemia are pernicious anemia and chlorosis, but splenic anemia may also be mentioned under this head.

(1)Progressive Pernicious Anemia.—It is frequently impossible to diagnose this disease from the blood examination alone. Severe secondary anemia sometimes gives an identical picture. Remissions, in which the blood approaches the normal, are common. All the clinical data must, therefore, be considered.

Hemoglobin and red corpuscles are always greatly diminished. In none of Cabot's 139 cases did the count exceed 2,500,000, the average being about 1,200,000. In more than two-thirds of the cases hemoglobin wasreduced to less extent than the red corpuscles: the color-index was, therefore, high. A low color-index probably indicates a mild type of the disease.

The leukocyte count may be normal, but is commonly diminished to about 3000. The decrease affects chiefly the polymorphonuclear cells, so that the lymphocytes are relatively increased. In some cases a decided absolute increase of lymphocytes occurs. Polymorphonuclear leukocytosis, when present, is due to some complication.

The red corpuscles show marked variation in size and shape (Plate VIII and Fig. 84). There is a decidedtendency to large oval forms, and despite the abundance of microcytes, the average size of the corpuscles is generally strikingly increased. Polychromatophilia and basophilic degeneration are common. Nucleated red cells are always present, although in many instances careful search is required to find them. In the great majority of cases megaloblasts exceed normoblasts in number. This ratio constitutes one of the most important points in diagnosis, since it is practically unknown in other diseases. Blood-plaques are diminished.

The rare and rapidly fatal anemia which has been described under the name ofaplastic anemiais probably a variety of pernicious anemia. Absence of any attempt at blood regeneration explains the marked difference in the blood picture. Red corpuscles and hemoglobin are rapidly diminished to an extreme degree. The color index is normal or low. The leukocyte count is normal or low, with relative increase of lymphocytes. Stained smears show only slight variations in size, shape, and staining properties of the red cells. There are no megaloblasts, and few or no normoblasts.

(2)Chlorosis.—The clinical symptoms furnish the most important data for diagnosis. The blood resembles that of secondary anemia in many respects.

The most conspicuous feature is a decided decrease of hemoglobin (down to 30 or 40 per cent. in marked cases), accompanied by a slight decrease in number of red corpuscles. The color-index is thus almost invariably low, the average being about 0.5.

As in pernicious anemia, the leukocytes are normal or decreased in number, with a relative increase of lymphocytes.

In contrast to pernicious anemia (and in some degree also to secondary anemia) the red cells are of nearly uniform size, are uniformly pale (Fig. 84), and their average diameter is somewhat less than normal. Changes in size, shape, and staining reactions occur only in severe cases. Erythroblasts are rarely present. The number of plaques is generally decreased.

(3)Splenic Anemia.—This is an obscure form of anemia associated with great enlargement of the spleen. It is probably a distinct entity. There is decided decrease of hemoglobin and red corpuscles, with moderate leukopenia and relative lymphocytosis. Osler's fifteen cases averaged 47 per cent. hemoglobin and 3,336,357 red cells. Stained films show notable irregularities in size, shape, and staining properties only in advanced cases. Erythroblasts are uncommon.

B. LEUKEMIA

Except in rare instances, diagnosis is easily made from the blood alone. Two types of the disease are commonly distinguished: themyelogenousand thelymphatic. Atypical and intermediate forms are not uncommon. Pseudoleukemia, because of its clinical similarity to lymphatic leukemia, is generally described along with leukemia.

1.Myelogenous Leukemia.—This is usually a chronic disease, although acute cases have been described.

Hemoglobin and red corpuscles show decided decrease. The color-index is moderately low.

Most striking is the immense increase in number of leukocytes. The count in ordinary cases varies between 100,000 and 300,000. Counts over 1,000,000 have beenmet. During remissions, the leukocyte count may fall to normal.

While these enormous leukocyte counts are equaled in no other disease, and approached only in lymphatic leukemia and extremely high-grade leukocytosis, the diagnosis, particularly during remissions, depends more upon qualitative than quantitative changes. Although all varieties are increased, the characteristic and conspicuous cell is the myelocyte. This cell never appears in normal blood; extremely rarely in leukocytosis; and never abundantly in lymphatic leukemia. In myelogenous leukemia myelocytes usually constitute more than 20 per cent. of all leukocytes. Da Costa's lowest case gave 7 per cent. The neutrophilic form is generally much more abundant than the eosinophilic. Both show considerable variations in size. Very constant also is a marked absolute, and often a relative, increase of eosinophiles and basophiles. Polymorphonuclear neutrophiles and lymphocytes are relatively decreased.

The red cells show the changes characteristic of a severe secondary anemia, except that nucleated reds are commonly abundant; in fact, no other disease gives so many. They are chiefly of the normoblastic type. Megaloblasts are uncommon. Blood-plaques are generally increased.

2.Lymphatic Leukemia.—This form may be either acute or chronic. There is marked loss of hemoglobin and red corpuscles. The color-index is usually moderately low.

The leukocyte count is high, but lower than in the myelogenous type. Counts of 100,000 are about the average, but in many cases are much lower. This highcount is referable almost wholly to increase of lymphocytes. They generally exceed 90 per cent. of the total number. In chronic cases they are chiefly of the small variety; in acute cases, of the large form. Myelocytes are rare.

The red corpuscles show the changes usual in severe secondary anemia. Erythroblasts are seldom abundant. Blood-plaques are decreased.

3.Pseudoleukemia(Hodgkin's disease) resembles lymphatic leukemia in that there is marked and progressive enlargement of the lymph-nodes. There is, however, no distinctive blood-picture. The changes in hemoglobin and red cells resemble those of a moderate symptomatic anemia, with rather low color-index. The leukocytes are commonly normal in number and relative proportions.

4.Anæmia Infantum Pseudoleukæmica.—Under this name von Jaksch described a rare disease of infancy, the proper classification of which is uncertain. There is enlargement of liver and spleen, and sometimes of lymph-nodes, together with the following blood-changes: grave anemia with deformed and degenerated red cells and many erythroblasts of both normoblastic and megaloblastic types; great increase in number of leukocytes (20,000 to 100,000), and great variations in size, shape, and staining of leukocytes, with many atypical forms and a few myelocytes.

The table on the following page contrasts the distinctive blood-changes in the more common conditions.

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