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Ehrlich, Paul / Histology of the Blood Normal and Pathological
. (This
book was produced from scanned images of public domain
material from the Google Print project.)



London: C. J. CLAY AND SONS,



Leipzig: F. A. BROCKHAUS.

Transcriber's note:

For Text: Words surrounded by a cedilla such as ~this~ signifies that
the words are bolded in the text. Words surrounded by underscores like
_this_ signifies the words are in italics in the text. Words surrounded
by equal signs (=like this=) means the letters in the words are spaced
out (gesperrt). For numbers and equations, carats before bracketed
numbers denote a superscript.

Minor typos have been corrected.







W. MYERS, M.A., M.B., B.Sc.







[_All Rights reserved._]



In no department of Pathology has advance been so fitful and interrupted
as in that dealing with blood changes in various forms of disease,
though none now offers a field that promises such an abundant return for
an equal expenditure of time and labour.

Observations of great importance were early made by Wharton Jones,
Waller, and Hughes Bennett in this country, and by Virchow and Max
Schultze in Germany. Not, however, until the decade ending in 1890 was
it realised what a large amount of new work on the corpuscular elements
of the blood had been done by Hayem, and by Ehrlich and his pupils. As
successive papers were published, especially from German laboratories,
it became evident that the systematic study of the blood by various new
methods was resulting in the acquisition of a large number of facts
bearing on the pathology of the blood; though it was still difficult to
localise many of the normal hæmatogenetic processes. The production of
the various cells under pathological conditions, where so many new
factors are introduced, must necessarily be enshrouded in even greater
obscurity and could only be accurately determined by patient
investigation, a careful arrangement and study of facts, and cautious
deduction from accumulated and classified observations.

The pathology of the blood, especially of the corpuscular elements,
though one of the most interesting, is certainly one of the most
confusing, of all departments of pathology, and to those who have not
given almost undivided attention to this subject it is extremely
difficult to obtain a comprehensive and accurate view of the blood in
disease. It is for this reason that we welcome the present work in its
English garb. Professor Ehrlich by his careful and extended observations
on the blood has qualified himself to give a bird's-eye view of the
subject, such as few if any are capable of offering; and his book now so
well translated by Mr. Myers must remain one of the classical works on
blood in disease and on blood diseases, and in introducing it to English
readers Mr. Myers makes an important contribution to the accurate study
of hæmal pathology in this country.

Comparatively few amongst us are able to make a cytological examination
of the blood, whilst fewer still are competent to interpret the results
of such an examination. How many of our physicians are in a position to
distinguish between a myelogenic leukocythæmia and a lymphatic leukæmia?
How many of us could draw correct inferences from the fact that in
typhoid fever there may not only be no increase in the number of certain
of the white cells of the blood, but an actual leukopenia? How many
appreciated the diagnostic value of the difference in the cellular
elements in the blood in cases of scarlet fever and of measles, and how
many have anything more than a general idea as to the significance of a
hypoleucocytosis or a hyperleucocytosis in a case of acute pneumonia, or
as to the relations of cells of different forms and the percentage
quantity of hæmoglobin found in the various types of anæmia?

One of the most important points indicated in the following pages is
that the cellular elements of the blood must be studied as a whole and
not as isolated factors, as "it has always been shown that the character
of a leukæmic condition is only settled by a concurrence of a large
number of single symptoms of which each one is indispensable for the
diagnosis, and which taken together are absolutely conclusive."
Conditions of experiment can of course be carefully determined, so far,
at any rate, as the introduction of substances from outside is
concerned, but we must always bear in mind that it is impossible, except
in very special cases of disease, to separate the action of the
bone-marrow from the action of the lymphatic glands; still, by careful
observation and in special cases, especially when the various organs and
parts may be examined after death, information may be gained even on
this point. By means of experiment the production of leucocytosis by
peptones, the action of micro-organisms on the bone-marrow, the
influence of the products of decaying or degenerating epithelial or
endothelioid cells, may all be studied in a more or less perfect form;
but, withal, it is only by a study of the numerous conditions under
which alterations in the cellular elements take place in the blood that
any accurate information can be obtained.

Hence for further knowledge of the "structure" and certain functions of
the blood we must to a great extent rely upon clinical observation.

Some of the simpler problems have already been flooded with light by
those who following in Ehrlich's footsteps have studied the blood in
disease. But many of even greater importance might be cited from the
work before us. With the abundant information, the well argued
deductions and the carefully drawn up statement here placed before us it
may be claimed that we are now in a position to make diagnoses that not
long ago were quite beyond our reach, whilst a thorough training of our
younger medical men in the methods of blood examination must result in
the accumulation of new facts of prime importance both to the
pathologist and to the physician.

Both teacher and investigator cannot but feel that they have now at
command not only accurate results obtained by careful observation, but
the foundation on which the superstructure has been built up--exquisite
but simple methods of research. Ehrlich's methods may be (and have
already been) somewhat modified as occasion requires, but the principles
of fixation and staining here set forth must for long remain the methods
to be utilised in future work. His differential staining, in which he
utilised the special affinities that certain cells and parts of cells
have for basic, acid and neutral stains, was simply a foreshadowing of
his work on the affinity that certain cells and tissues have for
specific drugs and toxins; the study of these special elective
affinities now forms a very wide field of investigation in which
numerous workers are already engaged in determining the position and
nature of these seats of election for special proteid and other poisons.

The researches of Metschnikoff, of Kanthack and Hardy, of Muir, of
Buchanan, and others, are supplementary and complementary to those
carried on in the German School, but we may safely say that this work
must be looked upon as influencing the study of blood more than any that
has yet been published. It is only after a careful study of this book
that any idea of the enormous amount of work that has been contributed
to hæmatology by Ehrlich and his pupils, and the relatively important
part that such a work must play in guiding and encouraging those who are
interested in this fascinating subject, can be formed.

The translation appears to have been very carefully made, and the
opportunity has been seized to add notes on certain points that have a
special bearing on Ehrlich's work, or that have been brought into
prominence since the time that the original work was produced. This
renders the English edition in certain respects superior even to the



This translation of the first part of _Die Anæmie, Nothnagel's Specielle
Pathologie und Therapie_, vol. VIII. was carried out under the personal
guidance of Professor Ehrlich. Several alterations and additions have
been made in the present edition. To my friend Dr Cobbett I owe a debt
of gratitude for his kind help in the revision of the proof-sheets.

W. M.





The quantity of the blood 2
Number of red corpuscles 4
Size of red corpuscles 12
Amount of hæmoglobin in the blood 13
Specific gravity of the blood 17
Hygrometry 21
Total volume of the red corpuscles 21
Alkalinity of the blood 23
Coagulability of the blood 24
Separation of the serum 24
Resistance of the red corpuscles 25



[alpha]. Preparation of the dry specimen 32
[beta]. Fixation of the dry specimen 34
[gamma]. Staining of the dry specimen 36
Theory of staining 37
Combined staining 38
Triacid fluid 40
Other staining fluids 41
Recognition of glycogen in the blood 45
Microscopic determination of the distribution of the
alkali of the blood 46


The red blood corpuscles 48
Diminution of hæmoglobin equivalent 49
Anæmic or polychromatophil degeneration 49
Poikilocytosis 52
Nucleated red blood corpuscles 54
Normoblasts and megaloblasts 56
The fate of the nuclei of the erythroblasts 57
The clinical differences in the erythroblasts 61



The lymphocytes 71
The large mononuclear leucocytes 73
The transitional forms 74
The polynuclear leucocytes 75
The eosinophil cells 76
The mast cells 76
Pathological forms of white blood corpuscles 77
The neutrophil myelocytes 77
The eosinophil myelocytes 78
The neutrophil pseudolymphocytes 78
Stimulation forms 79


[alpha]. The spleen 84
[beta]. The lymphatic glands 100
[gamma]. The bone-marrow 105


History of the investigation of the granules 121
Since Ehrlich. 123
Methods of demonstration 124
Vital staining of granules 124
The Bioblast theory (Altmann) 128
The granules as metabolic products of the cells (Ehrlich) 130
Secretory processes in granulated cells 134


Biological importance of leucocytosis 138
Morphology of leucocytosis 142
[alpha]. 1. Polynuclear neutrophil leucocytosis 143
Definition 143
Clinical occurrence 144
Origin 144
[alpha]. 2. Polynuclear eosinophil leucocytosis,
including the mast cells 148
Definition 149
Clinical occurrence 150
Origin 154
[beta]. Leukæmia ("mixed leucocytosis") 167
Lymphatic leukæmia 170
Myelogenous leukæmia 171
Morphological character 187
Origin 187


The blood platelets. The hæmoconiæ 190






In practical medicine the term "anæmia" has not quite the restricted
sense that scientific investigation gives it. The former regards certain
striking symptoms as characteristic of the anæmic condition; pallor of
the skin, a diminution of the normal redness of the mucous membranes of
the eyes, lips, mouth, and pharynx. From the presence of these phenomena
anæmia is diagnosed, and according to their greater or less intensity,
conclusions are also drawn as to the degree of the poverty of the blood.

It is evident from the first that a definition based on such a frequent
and elementary chain of symptoms will bring into line much that is
unconnected, and will perhaps omit what it should logically include.
Indeed a number of obscurities and contradictions is to be ascribed to
this circumstance.

The first task therefore of a scientific treatment of the anæmic
condition is carefully to define its extent. For this purpose the
symptoms above mentioned are little suited, however great, in their
proper place, their practical importance may be.

Etymologically the word "=anæmia=" signifies a want of the normal
=quantity of blood=. This may be "general" and affect the whole organism;
or "local" and limited to a particular region or a single organ. The
local anæmias we can at once exclude from our consideration.

_À priori_, the amount of blood may be subnormal in two senses,
quantitative and qualitative. We may have a diminution of the amount of
blood--"=Oligæmia=." Deterioration of the quality of the blood may be
quite independent of the amount of blood, and must primarily express
itself in a diminution of the physiologically important constituents.
Hence we distinguish the following chief types of alteration of the
blood; (1) diminution of the amount of Hæmoglobin (=Oligochromæmia=), and
(2) diminution of the number of red blood corpuscles (=Oligocythæmia=).

We regard as anæmic all conditions of the blood where a diminution of
the amount of hæmoglobin can be recognised; in by far the greater number
of cases, if not in all, Oligæmia and Oligocythæmia to a greater or less
extent occur simultaneously.

The most important methods of clinical hæmatology bear directly or
indirectly on the recognition of these conditions.

There is at present no method of ESTIMATION OF THE TOTAL QUANTITY OF THE
BLOOD which can be used clinically. We rely to a certain extent on the
observation of the already mentioned symptoms of redness or pallor of
the skin and mucous membranes. To a large degree these depend upon the
composition of the blood, and not upon the fulness of the peripheral
vessels. If we take the latter as a measure of the total amount of
blood, isolated vessels, visible to the naked eye, _e.g._ those of the
sclerotic, may be observed. Most suitable is the ophthalmoscopic
examination of the width of the vessels at the back of the eye. Ræhlmann
has shewn that in 60% of the cases of chronic anæmia, in which the skin
and mucous membranes are very white, there is hyperæmia of the
retina--which is evidence that in such cases the circulating blood is
pale in colour, but certainly not less in quantity than normally. The
condition of the pulse is an important indication of diminution of the
quantity of the blood, though only when it is marked. It presents a
peculiar smallness and feebleness in all cases of severe oligæmia.

The bleeding from fresh skin punctures gives a further criterion of the
quantity of blood, within certain limits, but is modified by changes in
the coagulability of the blood. Anyone who has made frequent blood
examinations will have observed that in this respect extraordinary
variations occur. In some cases scarcely a drop of blood can be
obtained, while in others the blood flows freely. One will not err in
assuming in the former case a diminution of the quantity of the blood.

The fulness of the peripheral vessels however is a sign of only relative
value, for the amount of blood in the internal organs may be very
different. The problem, how to estimate exactly, if possible
mathematically, the quantity of blood in the body has always been
recognised as important, and its solution would constitute a real
advance. The methods which have so far been proposed for clinical
purposes originate from Tarchanoff. He suggested that one may estimate
the quantity of blood by comparing the numbers of the red blood
corpuscles before and after copious sweating. Apart from various
theoretical considerations this method is far too clumsy for practical

Quincke has endeavoured to calculate the amount of blood in cases of
blood transfusion for therapeutic purposes. From the number of red blood
corpuscles of the patient before and after blood transfusion, the amount
of blood transfused and the number of corpuscles it contains, by a
simple mathematical formula the quantity of the blood of the patient can
be estimated. But this method is only practicable in special cases and
is open to several theoretical errors. First, it depends upon the
relative number of red blood corpuscles in the blood; inasmuch as the
transfusion of normal blood into normal blood, for example, would
produce no alteration in the count. This consideration is enough to shew
that this proceeding can only be used in special cases. It has indeed
been found that an increase of the red corpuscles per cubic millimetre
occurs in persons with a very small number of red corpuscles, who have
been injected with normal blood. But it is very hazardous to try to
estimate therefrom the volume of the pre-existing blood, since the act
of transfusion undoubtedly is immediately followed by compensatory
currents and alterations in the distribution of the blood.

No property of the blood has been so exactly and frequently tested as
convenience of the counting apparatus, and the apparently absolute
measure of the result have ensured for the methods of enumeration an
early clinical application.

At the present time the instruments of Thoma-Zeiss or others similarly
constructed are generally used; and we may assume that the principle on
which they depend and the methods of their use are known. A number of
fluids are used to dilute the blood, which on the whole fulfil the
requirements of preserving the form and colour of the red corpuscles, of
preventing their fusing together, and of allowing them to settle
rapidly. Of the better known solutions we will here mention =Pacini's= and
=Hayem's= fluids.

Pacini's solution. Hydrarg. bichlor. 2.0
Natr. chlor. 4.0
Glycerin 26.0
Aquæ destillat. 226.0

Hayem's solution. Hydrarg. bichlor. 0.5
Natr. sulph. 5.0
Natr. chlor. 1.0
Aquæ destillat. 200.0

For counting the white blood corpuscles the same instrument is
generally used, but the blood is diluted 10 times instead of
100 times. It is advantageous to use a diluting fluid which
destroys the red blood corpuscles, but which brings out the
nuclei of the white corpuscles, so that the latter are more
easily recognised. For this purpose the solution recommended by
Thoma is the best--namely a half per cent. solution of acetic
acid, to which a trace of methyl violet has been added[1].

The results of these methods of enumeration are sufficiently exact, as
they have, according to the frequently confirmed observations of R.
Thoma and I. F. Lyon, only a small error. In a count of 200 cells it is
five per cent., of 1250 two per cent., of 5000 one, and of 20,000
one-half per cent.

There are certain factors in the practical application of these methods,
which in other directions influence the result unfavourably.

It has been found by Cohnstein and Zuntz and others that the blood in
the large vessels has a constant composition, but that in the small
vessels and capillaries the formed elements may vary considerably in
number, though the blood is in other respects normal. Thus, for example,
in a one-sided paralytic, the capillary blood is different on the two
sides; and congestion, cold, and so forth raise the number of red blood
corpuscles. Hence, for purposes of enumeration, the rule is to take
blood only from those parts of the body which are free from accidental
variation; to avoid all influences such as energetic rubbing or
scrubbing, etc., which alter the circulation in the capillaries; to
undertake the examination at such times when the number of red blood
corpuscles is not influenced by the taking of food or medicine.

It is usual to take the blood from the tip of the finger, and only in
exceptional cases, _e.g._ in oedema of the finger, are other places
chosen, such as the lobule of the ear, or (in the case of children) the
big toe. For the puncture pointed needles or specially constructed
instruments, open or shielded lancets, are unnecessary: we recommend a
fine steel pen, of which one nib has been broken off. It is easily
disinfected by heating to redness, and produces not a puncture but what
is more useful, a cut, from which blood freely flows without any great

The literature dealing with the numbers of the red corpuscles in health,
is so large as to be quite unsurveyable. According to the new and
complete compilation of Reinert and v. Limbeck, the following figures
(calculated roundly for mm.^{3}) may be taken as physiological:


Maximum Minimum Average
7,000,000 4,000,000 5,000,000


Maximum Minimum Average
5,250,000 4,500,000 4,500,000

This difference between the sexes first makes its appearance at the time
of puberty of the female. Up to the commencement of menstruation the
number of corpuscles in the female is in fact slightly higher than in
the male (Stierlin). Apart from this, the time of life seems to cause a
difference in the number of red corpuscles only in so far that in the
newly-born, polycythæmia (up to 8-1/2 millions during the first days of
life) is observed (E. Schiff). After the first occasion on which food is
taken a decrease can be observed, and gradually (though by stages) the
normal figure is reached in from 10-14 days. On the other hand the
oligocythæmia here and there observed in old age, according to Schmaltz,
is not constant, and therefore cannot be regarded as a peculiarity of
senility, but must be caused by subsidiary processes of various kinds
which come into play at this stage of life.

The influence which the taking of food exercises on the number of the
red blood corpuscles is to be ascribed to the taking in of water, and is
so insignificant, that the variations, in part at least, fall within the
errors of the methods of enumeration.

Other physiological factors: =menstruation= (that is, the single
occurrence), =pregnancy=, =lactation=, do not alter the number of blood
corpuscles to any appreciable extent. The numbers do not differ in
arterial and venous blood.

All these physiological variations in the number of the blood
corpuscles, are dependent, according to Cohnstein and Zuntz, on
vasomotor influences. Stimuli, which narrow the peripheral vessels,
locally diminish the number of red blood corpuscles; excitation of the
vasodilators brings about the opposite effect. Hence it follows, that
the normal variations of the number contained in a unit of space are
merely the expressions of an altered distribution of the red elements
within the circulation, and are quite independent of the reproduction
and decay of the cells.

=Climatic conditions= apparently exercise a great influence over the
number of corpuscles. This fact is important for physiology, pathology,
and therapeutics, and has come to the front especially in the last few
years, since Viault's researches in the heights of the Corderillas. As
his researches, as well as those of Mercier, Egger, Wolff, Koeppe, v.
Jaruntowski and Schroeder, Miescher, Kündig and others, shew, the
number of red blood corpuscles in a healthy man, with the normal average
of 5,000,000 per mm.^{3}, begins to rise immediately after reaching a
height considerably above the sea-level. With a rise proceeding by
stages, a new average figure is reached in 10 to 14 days, considerably
larger than the old one, and indeed the greater the difference in level
between the former and the latter places, the greater is the difference
in this figure. Healthy persons born and bred at these heights have an
average of red corpuscles which is considerably above the mean; and
which indeed as a rule is somewhat greater than in those who are
acclimatised or only temporarily living at these elevations.

The following small table gives an idea of the degree to which the
number of blood corpuscles may vary at higher altitudes from the average
of five millions.

Author | Locality | Height above sea- | Increase of
| | level |
v. Jaruntowski | Görbersdorf | 561 metres | 800,000
Wolff and Koeppe | Reiboldsgrün | 700 " | 1,000,000
Egger | Arosa | 1800 " | 2,000,000
Viault | Corderillas | 4392 " | 3,000,000

Exactly the opposite process is to be observed when a person accustomed
to a high altitude reaches a lower one. Under these conditions the
correspondingly lower physiological average is produced. These
interesting processes have given rise to various interpretations and
hypotheses. On the one hand, the diminished oxygen tension in the upper
air was regarded as the immediate cause of the increase of red blood
corpuscles. Miescher, particularly, has described the want of oxygen as
a specific stimulus to the production of erythrocytes. Apart from the
physiological improbability of such a rapid and comprehensive fresh
production, one must further dissent from this interpretation, since the
histological appearance of the blood gives it no support. Koeppe, who
has specially directed part of his researches to the morphological
phenomena produced during acclimatisation to high altitudes, has shewn,
that in the increase of the number of red corpuscles two mutually
independent and distinct processes are to be distinguished. He observed
that, although the number of red corpuscles was raised so soon as a few
hours after arrival at Reiboldsgrün, numerous poikilocytes and
microcytes make their appearance at the same time. The initial increase
is therefore to be explained by budding and division of the red
corpuscles already present in the circulating blood. Koeppe sees in
this process, borrowing Ehrlich's conception of poikilocytosis, a
physiological adaptation to the lower atmospheric pressure, and the
resulting greater difficulty of oxygen absorption. The impediment to the
function of the hæmoglobin is to a certain extent compensated, since the
stock of hæmoglobin possesses a larger surface, and so is capable of
increased respiration. So also the remarkable fact may be readily
understood that the sudden rise of the number of corpuscles is not at
first accompanied by a rise of the quantity of hæmoglobin, or of the
total volume of the red blood corpuscles. These values are first
increased when the second process, an increased fresh production of
normal red discs, takes place, which naturally requires for its
developement a longer time. The poikilocytes and microcytes then vanish,
according to the extent of the reproduction; and finally a blood is
formed, which is characterised by an increased number of red corpuscles,
and a corresponding rise in the quantity of hæmoglobin, and in the
percentage volume of the corpuscles.

Other authors infer a relative and not an absolute increase in the
number of red corpuscles. E. Grawitz, for example, has expressed the
opinion that the raised count of corpuscles may be explained chiefly by
increased concentration of the blood, due to the greater loss of water
from the body at these altitudes. The blood of laboratory animals which
Grawitz allowed to live in correspondingly rarefied air underwent
similar changes. Von Limbeck, as well as Schumburg and Zuntz, object to
this explanation on the ground, that if loss of water caused such
considerable elevations in the number, we should observe a corresponding
diminution in the body weight, which is by no means the case.

Schumburg and Zuntz also regard the increase of red blood corpuscles in
the higher mountains as relative only, but explain it by an altered
distribution of the corpuscular elements within the vascular system. In
their earlier work Cohnstein and Zuntz had already established that the
number of corpuscles in the capillary blood varies with the width of the
vessels and the rate of flow in them. If one reflects how multifarious
are the merely physiological influences at the bottom of which these two
factors lie, one will not interpret alterations in the number of the red
corpuscles without bearing them in mind. In residence at high altitudes
various factors bring about alterations in the width of the vessels and
in the circulation. Amongst these are the intenser light (Fülles), the
lowering of temperature, increased muscular exertion, raised respiratory
activity. Doubtless, therefore, without either production of microcytes
or production _de novo_, the number of red corpuscles in capillary blood
may undergo considerable variations.

The opposition, in which as mentioned above, the views of Grawitz,
Zuntz, and Schumburg stand to those of the first mentioned authors,
finds its solution in the fact that the causes of altered distribution
of the blood, and of loss of water, play a large part in the sudden
changes. The longer the sojourn however at these great elevations, the
more insignificant they become (Viault).

We think therefore that from the material before us we may draw the
conclusion, that after long residence in elevated districts the number
of red blood corpuscles is absolutely raised. The therapeutic importance
of this influence is obvious.

Besides high altitudes, the influence of the tropics on the composition
of the blood and especially on the number of corpuscles has also been
tested. Eykmann as well as Glogner found no deviation from the normal,
although the almost constant pallor of the European in the tropics
points in that direction. Here also, changes in the distribution
occurring without qualitative changes of the blood seem chiefly

* * * * *

The same reliance cannot be placed on inferences based on the results of
the Thoma-Zeiss and similar counting methods for anæmic as for normal
blood, in which generally speaking all the red cells are of the same
size and contain the same amount of hæmoglobin. In the former the red
corpuscles, as we shall shew later, differ considerably one from
another. On the one hand forms poor in hæmoglobin, on the other very
small forms occur, which by the wet method of counting cannot even be

Apart even from these extreme forms, 1,000 =red blood corpuscles of
anæmic blood are not physiologically equivalent to the same number of
normal blood corpuscles=. Hence the necessity of closely correlating the
result of the count of red blood corpuscles with the hæmoglobinometric
and histological values. The first figure only, given apart from the
latter, is often misleading, especially in pathological cases.

It is therefore occasionally desirable to supplement the data of the
INDIVIDUALLY. This is effected by direct measurement with the ocular
micrometer; and can be performed on wet (see below), as well as on dry
preparations, though the latter in general are to be preferred on
account of their far greater convenience.

Nevertheless the carrying out of this method requires particular care.
One can easily see that in normal blood the red corpuscles appear
smaller in the thicker than they do in the thinner layers of the dry
preparation. We may explain this difference as follows. In the thick
layers the red discs float in plasma before drying, whilst in the
thinner parts they are fastened to the glass by a capillary layer.
Desiccation occurs here nearly instantaneously, and starts from the
periphery of the disc; so that an alteration in the shape or size is
impossible. On the contrary the process of drying in the thicker
portions proceeds more slowly, and is therefore accompanied by a
shrinking of the discs.

Even in healthy persons small differences in the individual discs are
shewn by this method. The physiological average of the diameter of the
greater surface is, according to Laache, Hayem, Schumann and others, 8.5
µ for men and women (max. 9.0 µ. min. 6.5 µ.) In anæmic blood the
differences between the individual elements become greater, so that to
obtain the average value, the maxima, minima, and mean of a large number
of cells, chosen at random, are ascertained. =But with a high degree of
inequality of the discs this microscopical measurement loses all
scientific value.=

However valuable the knowledge of the absolute number may be for a
judgment on the course of the illness, it gives us no information about
the AMOUNT OF HÆMOGLOBIN IN THE BLOOD, which is the decisive measure of
the degree of the anæmia. A number of clinical methods are in use for
this estimation; first direct, such as the colorimetric estimation of
the amount of hæmoglobin, secondly indirect, such as the determination
of the specific gravity or of the volume of the red corpuscles, and
perhaps also the estimation of the dry substance of the total blood.

Among the direct methods for hæmoglobin estimation, which aim at the
measurement of the depth of colour of the blood, we wish first to
mention one, which though it lays no claim to great clinical accuracy
has often done us good service as a rapid indicator at the bedside. A
little blood is caught on a piece of linen or filter-paper, and allowed
to distribute itself in a thin layer. In this manner one can recognise
the difference between the colour of anæmic and of healthy blood more
clearly than in the drop as it comes from the finger prick. After a few
trials one can in this way draw conclusions as to the degree of the
existing anæmia. Could this simple method which is so convenient, which
can be carried out at the time of consultation, come more into vogue, it
alone would contribute to the decline of the favourite stop-gap
diagnosis, 'anæmia.' For neurasthenic patients also, who so often fancy
themselves anæmic and in addition look so, a _demonstratio ad oculos_
such as this is often sufficient to persuade them of the contrary.

Of the instruments for measuring the depth of colour of the blood, the
double pipette of Hoppe-Seyler is quite the most delicate. A solution of
carbonic oxide hæmoglobin, accurately titrated, serves as the standard
of comparison. The reliable preparation and conservation of the normal
solution is however attended with such difficulties, that this method is
not clinically available. In the last few years, Langemeister, a pupil
of Kühne's, has invented a method for colorimetric purposes, also
applicable to hæmoglobin estimations. The instrument depends on the
principle, that from the thickness of the layer in which the solution to
be tested has the same colour intensity as a normal solution, the amount
of colour can be calculated. As a normal solution Langemeister uses a
glycerine solution of methæmoglobin prepared from pig's blood. To our
knowledge this method has not yet been applied clinically. Its
introduction would be valuable, for in practice we must at present be
content with methods that are less exact, in which coloured glass or a
stable coloured solution serves as a measure for the depth of colour of
the blood. There are a number of instruments of this kind, of which the
"hæmometer" of Fleischl, and amongst others, the "hæmoglobinometer" of
Gowers, distinguished by its low price, are specially used for clinical
purposes. Both instruments give the percentage of the hæmoglobin of
normal blood which the blood examined contains, and are sufficiently
exact in their results for practical purposes and for relative values;
although errors up to 10% and over occur with unpractised observers.
(Cp. K. H. Mayer.) Quite recently Biernacki has raised the objection to
the colorimetric methods of the quantitative estimation of hæmoglobin,
that the depth of colour of the blood is dependent not only on the
quantity of hæmoglobin but also on the colour of the plasma, and the
greater or less amount of proteid in the blood. These errors are quite
inconsiderable for the above-mentioned instruments, since here the blood
is so highly diluted with water that the possible original differences
are thereby reduced to zero.

Among the methods for indirect hæmoglobin estimation, that of
calculation from the amount of iron in the blood appears to be quite
exact, since hæmoglobin possesses a constant quantity of iron of 0.42
per cent. This calculation may be allowed in all cases for normal blood,
for here there is a really exact proportion between the amounts of
hæmoglobin and of iron. Recently A. Jolles has described an apparatus
for quantitative estimation of the iron of the blood, called a
"ferrometer;" which renders possible an accurate valuation of the iron
in small amounts of blood. However for pathological cases this method of
hæmoglobin estimation from the iron present is not to be recommended.
For if one tests the blood of an anæmic patient under the microscope for
iron one finds the iron reaction in numerous red blood corpuscles.

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