four varieties of blood-corpuscles in the body: (1) red, (2) white, (3)
nucleated red, and (4) the hæmatoblasts (Hayem), or blood-plates of
Bizzozero.
(1) Red Corpuscles.--In each cubic millimeter of plasma there are about
5,000,000 red cells. The percentage may vary within health limits from
90 to 110. The corpuscles are circular, non-nucleated, biconcave disks,
homogeneous, to ordinary inspection structureless, and consist of a
colorless stroma which is possibly reticulated, and a red coloring
matter, the hæmoglobin. In {883} health they are tolerably uniform in
size, about 7.9 µ[1] in diameter, or in English measurement 1/3200 of
an inch (Gulliver). Even in normal blood there may be slight variations
in size between 6.5 µ and 8.5 µ, the average, according to Hayem, being
7.5 µ.
[Footnote 1: µ is used to signify a micro-millimeter or 1/1000 part of
a millimeter.]
(2) Colorless or white corpuscles, nucleated masses of protoplasm, with
an average diameter of 10 µ, or about 1/2500 of an inch. The majority
have a finely granular protoplasm, but in a few the granules are coarse
and do not completely fill the clear protoplasm. The ultimate structure
is reticular (Heitzman). Erhlich[2] has shown by their varying reaction
to eosin that there are chemical differences among the colorless cells
quite unrecognizable by other means. In healthy blood they display
active amoeboid changes at ordinary temperatures. Their protoplasm does
not, as is commonly stated, rapidly disintegrate, but if kept at a
medium temperature retains its vitality, as shown by movements, for
hours. The number per cubic millimeter is from 8 to 15 millions, and
the ratio to the red is variously computed as 1 to 300 or 1 to 500.
[Footnote 2: _Frerichs find Leyden's Archiv_, Bd. i.]
(3) Nucleated red corpuscles, which occur in the blood of the foetus
and the infant, gradually diminishing until at the third or fourth year
they disappear. In the adult they do not occur in the blood in health,
but are normal constituents of the red marrow of the short bones. They
measure from 1/1500 to 1/2000 of an inch, and are of somewhat variable
intensity of color, often quite as deep as the ordinary red forms.
There may be two or even three nuclei, not colored, grouped together,
often eccentric, and in some instances protruding from the cell.
(4) The hæmatoblasts of Hayem, the blood-plates of Bizzozero, the
elementary or intermediate corpuscles, are small discoid colorless
corpuscles about 3 µ in diameter, and are normal constituents of
healthy blood. When the blood is withdrawn, they aggregate together
into irregular clumps or masses, which have long been known as
Schultze's granule-masses. It can be readily demonstrated in new-born
rats or kittens, in which these masses abound, that the corpuscles
composing them are isolated in the vessels, and only run together when
the blood is drawn. The statement is commonly made that the
granule-masses of Schultze result from the disintegration of the white
corpuscle (of the red, Erhlich), but half an hour's study of the
question in a new-born rat will convince any competent histologist that
we have here to do with a separate blood-element.[3] It appears to have
important relations with the production of fibrin.
[Footnote 3: Consult _Proceedings Royal Society_, 1874; _Centralblatt
f. d. Med. Wissenschaften_; _Medical News_, 1882, 2; Bizzozero,
_Virchow's Archiv_, Bd. xi.; Hayem, _Recherches sur l'Anatomie normal
et pathologique du Sang_, Paris, 1878.]
Of the origin and life-history of the red corpuscles during
post-embryonic life we have still much to learn. They are stated to
develop--
(1) From colorless corpuscles, the lymph-cells or leucocytes. In the
lymph-glands, the Malpighian bodies of the spleen, in the thymus, or
the adenoid tissue of the tonsil, of the lymph-elements in the
intestines and other regions, colorless cells are constantly being
manufactured, and the general belief has been since Hewson's time that
the red corpuscles develop in some way or other from these leucocytes.
How or where has not yet been settled. It does not apparently go on in
the blood, or we should surely catch, in the many observations and with
the excellent powers now in use, a glimpse of the birth of one of them.
Some observers (Johnstone[4]) maintain that they develop from the
granular protoplasm of the adenoid reticulum by a process of budding.
This may be so, but we should expect to find the lymph in the efferent
{884} vessels and of the thoracic duct much more rich in red cells than
is usually the case, and in specimens of healthy glands we should find
young-looking elements such as he describes.
[Footnote 4: _Seguin's Archiv_, vol. vi.]
(2) From the nucleated red corpuscles. In the embryo this undoubtedly
takes place, and as the weeks of development proceed, the ordinary red
forms gradually predominate. In the child the red nucleated cells
disappear early, and are then found only in the red marrow. So far as
my observations go,[5] they apparently originate from colorless
marrow-cells, which gradually become more homogeneous, and hæmoglobin
develops in the protoplasm. The nucleus degenerates and disappears,
when the cell has the appearance of an ordinary red disk. Rindfleisch
thinks that the nucleus of the nucleated red is extruded in the
development. It is possible that from these nucleated red corpuscles
cells may originate in another way--viz. by budding. This I have seen
and sketched in the marrow-cells,[6] and Malassez has studied the same
process.[7] The gemmæ are small, and sprout from the protoplasm, not
the nuclei, and when they break off they resemble the microcytes which
occur so abundantly in certain anæmic states. Bizzozero[8] holds that
these nucleated red corpuscles are independent elements which do not
develop from the colorless marrow-cells. They multiply by fission, and
develop into the ordinary red forms with the disappearance of the
nuclei. Several recent investigations support this view.[9]
[Footnote 5: _Centralblatt f. d. Med. Wissensch._, 1878.]
[Footnote 6: _Trans. Am. Ass. Ad. Science_, 1882.]
[Footnote 7: _Archives de Physiologie_, 1882.]
[Footnote 8: _Centralblatt f. d. Med. Wissenschaften_, Bd. xix.]
[Footnote 9: _Fortschritte der Medicin_, 1885, No. 1.]
(3) Hayem believes that the red corpuscles develop from the small
hæmatoblasts, but, so far as I know, his observations have never been
confirmed. He states that in normal blood they occur in the proportion
of about 1 to 20 red. In all states of blood reparation they increase
greatly. He describes a hæmatoblastic crisis as occurring after
hemorrhage, fevers, etc., when the number of these elements rapidly
augments, and is succeeded by the addition of many small pale-red
corpuscles, which he looks upon as intermediate between the
hæmatoblasts and the ordinary red forms.
The colorless corpuscles are regarded as the direct offspring of the
cells of the follicular cords in the lymph-glands and adenoid tissue,
but whether by process of division of existing leucocytes or by
sprouting from the endothelial places, or from the protoplasm in the
fibres of the reticulum, remains to be settled.
The nucleated red corpuscles are in the healthy adult confined to red
marrow, in which they probably develop from colorless cells, and may be
regarded, as Neumann originally suggested, as transitional or
intermediate forms between white and red cells. In anæmic states they
may occur in the spleen and in the lymph-glands.
Of the origin of the hæmatoblasts or blood-plates we know absolutely
nothing. They occur most abundantly under two most opposite
conditions--in the young growing animal just entering upon life, and in
the diseased, cachectic, wornout animal just preparing to abandon it.
Our knowledge of the relation of the cytogenetic organs to
blood-formation may be thus briefly stated: The spleen certainly takes
part in the development of colorless corpuscles, but its participation
in red blood-formation is more doubtful. The nucleated red or embryonal
forms do not occur, at least in any numbers, in health, though some
observers have noted that after a repeated bleeding the organ was
swollen and contained many such cells, as if it was the seat of an
active development. Though the opinion prevails widely that the spleen
is one of the important organs in the formation of red corpuscles, the
evidence for this belief is of an exceedingly scanty nature.
The lymphatic glands and the adenoid tissue in other regions are the
seats {885} of constant production of colorless corpuscles, but of
their relation to the red corpuscles there is the same lack of
information as in the spleen. I do not know of any corroboration of the
observation of Johnstone above mentioned, and in any case the number of
red cells in the efferent vessels of a lymph-gland is so small--and
indeed in the thoracic duct itself--that we cannot believe they are
produced as red corpuscles in large numbers within the lymphatic
system.
The red bone-marrow, as pointed out by Neumann[10] and Bizzozero,[11]
appears to be the seat of blood-formation, and in the adult body is the
only region in which the embryonic or nucleated red cells are found. It
is a tissue similar in many respects to the spleen, and, though
confined to the short and flat bones, the total amount in the body is
very considerable. In the young it also fills the long bones. The
evidence of the development of red corpuscles in the marrow rests upon
the constant presence of nucleated cells infiltrated with hæmoglobin,
and of their fission. Forms undergoing the process of karyokinesis can
be seen without difficulty. In excessive hemorrhage, natural or
induced, it appears to undergo an active proliferation, and in the long
bones a red marrow may replace the fatty tissue.
[Footnote 10: _Centralblatt f. d. Med. Wissenschaften_, 1868.]
[Footnote 11: _Ibid._, 1868.]
The liver is doubtless the seat of blood-destruction, for the
bile-pigments and leucocytes with red corpuscles in their interior have
been found in its tissue. Nicolaides[12] has shown that in the blood of
the hepatic vein there may be a reduction of from one million to one
million and a half of red corpuscles per c.m. In the embryo Neumann[13]
has shown that it may be the seat of the production of corpuscles, but
there is no satisfactory evidence that in the adult this ever takes
place.
[Footnote 12: _Archives de Physiologie_, 1882.]
[Footnote 13: _Archiv der Heilkunde_, xv.]
The remarkable rapidity with which, after a profuse bleeding, the
normal proportion of red corpuscles is reached shows with what activity
the development may proceed, and how favorable the conditions must be
for their production. After the loss of a large quantity of blood the
manufacture of new corpuscles may proceed at the rate of 30,000,
40,000, or even 50,000 a day.
What becomes of the red corpuscles? Here, again, is a question not
satisfactorily settled. We do not know the average length of life of
corpuscles. They are supposed to be short-lived--three weeks, according
to Quincke. The need for their dissolution is assumed to provide
pigment for the various secretions and tissues, and we occasionally see
a few cells in the blood with a pallor which may be regarded as an
indication of senility.
Positive evidence, however, of their destruction is afforded by the
occurrence of the so-called corpuscles containing red corpuscles, which
occur normally in red marrow and in the spleen, and under some
circumstances in the lymphatic glands and liver. The red cells undergo
gradual transformation into a yellow granular, and finally black,
pigment. In normal spleen and marrow the numbers found are very
variable; in fevers and cachectic states they may be in extraordinary
numbers. Quincke and his pupil Peters[14] have studied with great care
this process of transformation of the red corpuscles and accumulation
of the pigment in the cells of the marrow, spleen, liver, and
lymph-glands, to which the term siderosis is applied. These
pigment-granules are in the form of an iron albuminate, and are used in
the development of new corpuscles. Thus, after repeated bleedings in
animals, they may disappear completely in the restoration of the blood,
while in animals into whose vessels blood has been transfused or
injected subcutaneously the iron-containing cells in the various organs
are very numerous, and even the cortical cells of the kidney contain
numerous granules.
[Footnote 14: _Deutsches Archiv f. klin. Med._, Bds. xxv., xxvii.,
xxxii., xxxiii.]
The amount of hæmoglobin in 100 grammes of healthy blood is {886} 13.45
grm. (Preyer). Malassez estimated the quantity in a cubic millimeter of
blood at between 0.125 and 0.134 milligramme, and, taking the
corpuscular richness at from 4,000,000 to 4,600,000, he has estimated
approximately the amount of hæmoglobin in each corpuscle.
PLETHORA.
General and persistent polyæmia or plethora has scarcely a place in
recent pathology. Formerly it was thought that either from
over-production or lowered expenditure the total amount of blood
accumulated and filled the blood-vessels to an abnormal extent. The
amount of blood undergoes, within limits, constant daily alterations,
and after a full meal the vessels are in a state of plethora compared
with their condition at the end of a ten hours' fast. If a
plethysmograph could be devised to record graphically the variations in
the total quantity of blood, each ingestion of food or drink into the
vessels would be followed by a rise, and each interval by a gradual
decline. So long as the organs of secretion and excretion are active
the quantitative and qualitative condition of the blood is maintained
at a tolerably uniform standard in each individual. At different
periods of life the relation of blood-weight to body-weight varies. In
the new-born the blood amounts to one-eighteenth part by weight of the
body, while in the adult the average is from one-twelfth to
one-fourteenth; so that in the infant there is a condition of
comparative plethora. There are no reliable observations on the
proportion of blood- to body-weight at respective ages, but there
appears to be a reduction in old age. In women it is stated that just
before each menstrual period there is a state of polyæmia.[15]
[Footnote 15: Mary Putnam Jacobi, _The Question of Rest for Women_, New
York.]
Worm-Müller[16] and Cohnheim[17] have made some very interesting
experiments on this question of plethora. By transfusion in dogs a
state of artificial plethora is readily established, and the animals
stand the injection of as much as 10 or 12 per cent. of the body-weight
of blood, above which quantity a fatal result ensues. After an
injection of 20 or 30 per cent. of the total amount of blood, the
superfluous plasma and corpuscles are got rid of in a few days, while
with a larger injection of 60 to 80 per cent. it takes two or three
weeks before the normal state is again reached. The albuminous and
nitrogenous materials are largely got rid of by the urine, which
increases rapidly in quantity and also in the amount of urea. The
excess of corpuscles gradually disappears, and the hæmoglobin becomes
deposited, as Quincke has shown, in the form of small granules in the
cells of the liver, spleen, and bone-marrow.
[Footnote 16: _Transfusion and Plethora_, Christiania, 1875.]
[Footnote 17: _Allgemeine Pathologie_, 2te Auflage.]
In a similar way, it is reasonable to think that the body is quite
capable of disposing of surplus albuminous materials in over-fed, lazy
individuals with active digestion, whose red faces, full vessels, and
bounding pulses give the impression of a distended circulatory system,
and whom we term plethoric. Their appearance is the result rather of
blood-distribution than of actual increase in the total volume, and
there is no evidence that under any circumstances a rich and abundant
diet without much exercise can permanently increase the amount of
blood. It was formerly held that the healing of an old sore or the
cessation of an accustomed discharge or loss of blood, by diminishing
expenditure while the blood-making power was maintained, could induce
plethora if no local disorder was excited "before the vessels {887} in
general reached a state of plethoric tension." Of such a condition, and
of the plethora apocoptica that was thought to occur after the
amputation of a limb, we do not hear much now, and the prevalent
opinion of pathologists is expressed by Cohnheim, when he says "that,
except as a transitory state, polyæmia does not occur under any
circumstances." What, then, is the meaning of the full-blooded,
rubicund condition which we see in some men, not necessarily large
feeders, but often with vigorous active constitutions and perfect types
of health? The appearance of plethora is caused chiefly by the
distension of the superficial vessels; the circulation of the skin is
remarkably active, particularly in the face, and it is probable that we
have here to deal with local peculiarities of the vessels or of their
innervation, and not with any general augmentation of the total
blood-mass. It may be, however, that in such persons there is a
plethora of certain of the constituents of the blood--viz. the red
corpuscles--and there may be a state of polycythæmia rubra, as it has
been called, in which the percentage of red cells is increased. In
several such cases I have found, as has been previously noted, the
number of red corpuscles considerably over the average. A relative
increase in the number of red corpuscles also occurs in those sudden
and excessive losses of fluid, as in cholera, in which the blood may
become thick and sticky from the great reduction in the plasma,
particularly of the water and salts--anhydræmia--or in cases in which
the income of fluid is greatly restricted. Henry (F. P.) has recorded a
case[18] of stenosis of the cardia, in which, with great emaciation,
the corpuscles per c.m. were 5,525,000.
[Footnote 18: _Archives of Medicine_, New York, vol. vii.]
The condition known as hydræmic plethora develops whenever there is a
great reduction in the number of corpuscles, as after a hemorrhage, or
when the blood has been impoverished by long-standing suppuration,
albuminuria, or in the growth of large tumors. So also when the
secretion of urine is diminished, as in some cases of Bright's disease,
and at the same time charged with albumen, the blood may become very
watery; but in these states there is not an absolute increase in the
entire blood, but only a relative excess of the water. Occasionally,
this great excess can be noticed in the blood-drop as it comes from the
finger-tip; the corpuscles do not fill the entire drop, and
consequently leave irregular areas unoccupied by the red disks.
ANÆMIA.
A reduction in the amount of the blood or of its corpuscles occurs
under a great variety of circumstances. Broadly speaking, we can
recognize two great clinical and pathological groups of cases: I. Those
induced by causes acting upon the blood itself; and, II. Those induced
by disturbance in the functions of the blood-making organs.
I. Of causes acting directly upon the blood, we shall consider--
1st. Hemorrhage, traumatic or spontaneous. A high grade of anæmia may
be quickly produced by loss of a large quantity of blood, and the
reduction is in all the constituents; there is a true oligæmia. If the
amount lost be excessive, death results from the diminution in the
total volume of blood and general lowering of the arterial pressure. If
the hemorrhage is sudden and profuse, as from a large vessel, the loss
of four or five pounds of blood, or even less, may be sufficient to
induce fatal syncope. In hemorrhage into the pleura or peritoneum from
rupture of aneurisms, etc., it is rare to meet with more than three or
four pounds of clot and serum; seven and a half {888} pounds is the
largest amount I know of shed into one of the cavities (pleura) by
rupture of an aneurism. When the bleeding extends over several days,
the amount lost may be very much greater. In cases of hæmophilia
extraordinary accounts are given of the amount collected in the course
of a few days. In a case of hæmoptysis a patient lost over ten pounds
by measurement in one week, and then recovered from the immediate
effects. After the most severe hemorrhages the reduction in the number
of red corpuscles is not nearly so great as in forms of idiopathic
anæmia. Thus in the case just mentioned at the termination of the week
of bleeding there were 1,390,000 red corpuscles to the cubic
millimeter. In any single bleeding a fatal result follows the loss of
one-third or one-half of the total blood-volume. The process of
regeneration of the blood goes on with astonishing rapidity, and in
some bleeders a week or ten days will suffice to re-establish the
normal amount. The restitution begins even during a hemorrhage by the
absorption of lymph from the tissues under the lowered pressure in the
vessels. The dryness and stickiness of the serous membranes after death
from a profuse hemorrhage is usually very marked. The water and saline
constituents of the blood are readily restored by absorption from the
gastro-intestinal tract. The albuminous elements are also quickly
renewed, but it may take weeks or months before the number of
corpuscles reaches the normal standard. Indeed, this condition of
oligocythæmia, as it is called, may persist, grow worse, and ultimately
prove fatal. The microscopical characters of the blood after severe
hemorrhage are not much changed, except as regards the white
corpuscles, which are relatively increased, and the fibrin network,
which is much less marked than in health. The white corpuscles may be
very slightly reduced in number per cubic millimeter--a fact to be
accounted for either by a relatively diminished loss during the
bleeding, owing to their adhesiveness and wall-loving properties, or to
a quick restitution from the lymph which is poured into the
blood-stream. It has been observed both in dogs and men by Lyon[19]
that after a severe hemorrhage the number of red per cubic millimeter
diminished for several days after the bleeding had been checked. How
and where does the regeneration of red corpuscles take place after a
severe hemorrhage? One would think that under these circumstances, if
any, we should be able to get information which might be of service in
determining the problem of blood-development; but, in spite of the
numerous experiments on the subject, we are still far from a knowledge
of full details. The observations of Neumann,[20] Litten and Orth,[21]
Bizzozero,[22] Lepine,[23] and others appear to prove conclusively that
the bone-marrow plays an important part in the formation of the new red
disks, becoming lymphoid, losing its fat, and the nucleated red cells
increase enormously. The same process has been observed in many cases
in man. In a case of profuse metrorrhagia with profound anæmia
Neumann[24] found the marrow in all the bones of a rich raspberry red,
full of the nucleated forms, which were also very abundant in the
blood, and more in the vena azygos than in the aorta. The evidence in
favor of the active participation of the spleen is not so conclusive.
Neumann[25] concludes that the spleen takes no share in the process,
and holds that the nucleated red cells found in it are probably derived
from the bone-marrow. Bizzozero, on the other hand, has found the
spleen swollen and showing signs of lively blood-formation. He states
that after removal of the spleen the restitution of the red corpuscles
takes place much more slowly. Pouchet, on the contrary, says the
regeneration goes on just as rapidly without the spleen. {889} Of the
action of the lymph-glands there is even less evidence. They have been
found swollen, but in traumatic anæmia I do not know of any
observations on their swelling and conversion into a red spleen-like
tissue, such as have been found in some cases of idiopathic anæmia.
[Footnote 19: Of Norwich, Conn.: _Virchow's Archiv_, lxxxiv.]