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ANEMIA.
V
     FREDERICK  P. HENRY, M.D.,


PROF. OF CLINICAL MEDICINE IN THE PHILADELPHIA POLY-
 CLINIC; ONE OF THE PHYSICIANS TO THE EPISCOPAL HOS-
 PITAL; ONE OF THE PHYSICIANS TO THE PHILADELPHIA
  HOSPITAL ; CONSULTING PHYSICIAN TO THE HOME FOR
   CONSUMPTIVES ;  CORRESPONDING MEMBER OF THE
    ROYAL MEDICAL ACADEMY OF ROME, ETC., ETC.
REPRINTED FROM
THE  POLYCLINIC
          PHILADELPHIA:
P. BLAKISTON, SON  &  CO.,
       No. 1012 Walnut Street.
               1887. 
         MbZlcL,






    Copyright, 1887, by.
P. BLAKISTON, SON & CO. 
                   too

     DR. S. WEIR MITCHELL,

THIS WORK IS, BY PERMISSION, RESPECTFULLY
               DEDICATED.
' Semper honos, nomenque tuum, laudesque manebunt,
 Qux me cunque terrx vocant." 
 
PREFACE.
  This, the first systematic treatise on anaemia
published in this country, is a reprint of a series
of articles published in The Polyclinic dur-
ing the past year, and embodies the  results
of many years' study of the blood and the dis-
orders consequent upon its imperfect elabora-
tion.  The statements  which  it contains  are,
for the most part, based upon personal obser-
vation, and where this has been wanting, upon
accepted  facts  of physiology  and  pathology.
I have  endeavored  to supply the  want of a
trustworthy guide to a wide and growing field
of  research—a  want  which  I myself have
keenly felt.
  721 Pine Street, June 1st, 188/.
                     v 
 
CONTENTS.
                                           PAGE
Introduction................    I
Methods of Examination,.........   io
Anaemia in General,............   15
Exciting Causes of Anaemia,........   20
Symptoms of Anaemia,...........   27
Anatomical Characters of Aiuvmia,.....   30
Diagnosis  of Anaemia,...........   31
Prognosis of Anaemia,...........   34
Treatment of Anaemia in General,  ......   35
Varieties of Anaemia,...........   43
Chlorosis,  Anaemia of Puberty,.......   47
Anaemia Lymphatica,...........   59
Leucocythaemia,.............   75
Anaemia Splenica,............102
Pernicious Anemia,............114
Secondary Anaemia,............129
Toxanaemia,  .  ..............130
Parasitic Aneemia,............132
Index,.................135
                       vii 
 
ANEMIA.
               INTRODUCTION.
  The blood holds in solution certain albumin-
ous bodies, of which the principal are serum-
albumin, serum-globulin, and fibrinogen, and a
number  of mineral  substances,  the  chief  of
which are common salt (sodium chloride) and
sodium carbonate. These may  be  classed  as
the invisible constituents of the blood, and their
investigation  belongs to the  domain  of the
physiological chemist.   In addition, it holds  in
suspension  certain bodies, the  red  and  white
corpuscles, which are open to direct inspection,
and may, therefore, be  classed  as the visible
constituents of the blood.  The study of  these
latter, as regards their form, color, size, number
and relative proportion, is the  province of the
histologist, and it  is with these  properties that
we are concerned in this treatise.
  The red corpuscles of man are circular disks,
with rounded edges and depressed centres. On
account of the difference in thickness between
      A              1 
2
the central and peripheral  parts of a red cor-
puscle, it is impossible that its  entire surface
can be accurately focused  by the microscope
at the same  time, and, accordingly,  when its
centre appears bright its periphery is dark, and
vice versa.   The diameter of the human red
corpuscle is about T|^ of a millimetre, or ^Vtr ot
an inch.  The chemistry  of the red corpuscles
is quite complex, and, in  some respects, still
unsettled.   The  most  important  ingredient,
haemoglobin, is conspicuous by its brilliant op-
tical properties, and its amount  may  be most
readily determined by these alone.   It is the
only proteid of the body that contains iron, and
the amount of this mineral in the  ash of the
blood  affords a method of determining the
amount of  haemoglobin in  a given specimen.
It is by means of the haemoglobin in the red
corpuscles  that the blood conveys  oxygen  to
the tissues.   Haemoglobin is  characterized by
the readiness with which it absorbs and parts
with oxygen.   It exists in the blood  in two dis-
tinct forms : in the arterial blood as oxy-haemo-
globin, and in the  venous blood  as reduced
haemoglobin.   These two  forms  are readily
distinguished by  means  of the spectroscope. 
3
Haemoglobin is crystallizable, the crystals being
obtained with greater or less ease from the blood
of different animals.   They may  be obtained
most readily from the blood of the rat, by simply
mixing it with distilled water on  a glass slide.
Other means employed with the blood of other
animals are : alternate freezing and  thawing of
the blood, the passage through it  of electric
shocks, of the vapors of ether and chloroform,
and the addition of the alkaline salts of the bile.
The  largest crystals are  deposited from blood
that is allowed to undergo decomposition.  Thus
obtained, they are often of enormous size—from
three to five centimetres long. This is explained
by the  supposition  that putrefaction  destroys
substances which are preventive of  crystalliza-
tion.  If there is any single element of the body
that deserves to be called "vital," it is undoubt-
edly haemoglobin.   It is  universally  present,
and conveys to the tissues the element, oxygen,
that is most essential to the life of the individual,
while its  diminution below  the  normal,  even
when slight, is manifested by various symptoms
of functional  disorder, and when  extreme  and
long continued, leads to grave  and irreparable
organic lesions.   Its  chemical properties are 
4
extraordinary,  and  apparently  contradictory.
It  is organic and yet crystallizable;  it has an
eager affinity for oxygen, and  yet parts with  it
on the slightest demand; it is soluble in water,
and circulates in the blood without leaving the
red corpuscles; and, finally, without losing its
identity, it exists in the blood in two distinct
forms :  in the arteries as  oxy-haemoglobin, in
the veins as reduced haemoglobin.   The  ab-
sence of this substance from the blood in greater
or less degree, is at the root of the various  forms
of anaemia, about to be considered.
  The white, or colorless corpuscles, are spher-
ical masses  of granular, nucleated protoplasm,
having a diameter of io/j-* or 25V5 of an inch.
They ppssess the power of spontaneous move-
ment, and hence are sometimes called amoeboid
cells, from their resemblance, in this respect, to
the unicellular rhizopod,  called  the  amceba.
They exist in healthy blood  in about the pro-
portion of one white to five  hundred red cor-
puscles.  Their  specific  gravity is  less than
that of the red  corpuscles,  and, therefore,  if
blood be placed in a narrow cylindrical vessel
 * The Greek letter, fi, is used as  the sign of the micromilli-
metre, or one-thousandth of a millimetre. 
5
and kept from coagulating by a temperature a
little above  the  freezing point, or by the addi-
tion of a saline, such as  sodium sulphate, the
red corpuscles will collect at the bottom of the
vessel, and  the  white at the top.   Owing to
their scanty  numbers, great difficulty stands in
the way of  their accurate chemical analysis.
Nevertheless,  some  work has been   accom-
plished  in   this  direction.   Their contractile
power is probably dependent upon a substance
closely  resembling the  myosin of voluntary
muscle.  Their  nuclei  may  be isolated from
the surrounding protoplasm  by the action of
gastric juice, which dissolves the  protoplasm
and leaves  the  nucleus  intact.  The  latter is
composed of a mucin-like substance,  contain-
ing phosphorus, called nuclein.  The minute
granules scattered  throughout the  substance of
the white corpuscles are, some of them, soluble
in ether and alcohol, and therefore regarded as
fat granules;  the  nature of the granules  not
thus dissolved is unknown.  Glycogen is also
contained in the white  corpuscles, as  may be
demonstrated  by  treating them with  a solu-
tion of one  part iodine,  and two parts potas-
sium iodide, in one hundred parts water. 
6
  Besides the red and white corpuscles, other
morphological elements exist in the blood, con-
cerning the character and  function of which
there exists considerable confusion.  They are
the haematoblasts of Hay em, identical with the
blood-plates (Blutplattchen) of  Bizzozero, the
microcytes, and the advanced lymph  disk or
invisible corpuscle  of Norris.  When blood is
examined under the microscope, there may be
occasionally observed, and sometimes in large
numbers, certain  granular-looking masses of
irregular shape, the size of which is variable,
but may considerably exceed that of the white
corpuscles.   They are known  as  Schultze's
granule  masses.   With  strong  lenses,  it  is
readily  seen that  they are not  granular  or
amorphous—like the amorphous urates seen in
urine—but are  composed of distinct and inde-
pendent individual elements,* which latter are
the haematoblasts or blood-plates.  " They are
the elementary corpuscles of Zimmermann, the
globulins of Donne, the grains sarcodiques of
Vulpian, and the granulations  libres  of Ran-
vier.  The latter regarded them as particles of
fibrin, which serve as centres  of coagulation,
* This was first demonstrated by Osier. 
7
just  as  a crystal of sodium sulphate dropped
into  a  solution of  the  same will  serve as a
centre of crystallization." *
  These bodies are not,  as has been supposed,
disintegration products of the white corpuscles,
for they may be seen circulating in the blood
of transparent tissues, such as the mesentery.
Their function is intimately concerned with the
production of fibrin.
  The  microcytes  are  round or  disk-shaped
bodies,  much smaller than the red corpuscles.
They vary considerably in  size, their average
diameter being 3/*.   They resemble minute red
corpuscles, and sometimes  contain considerable
coloring matter.  They  are  very numerous in
idiopathic, so-called pernicious, anaemia, while,
on the other hand, the granule masses  are but
scantily present  in  that disease.   Microcytes
are also to be found in perfectly healthy blood.
  The colorless corpuscle of Norris is a red cor-
puscle minus its coloring matter.  Norris claims
that  it is a young red disk that has been elabo-
rated in the lymph glands, and has entered the
blood by the thoracic duct, and  that it  gradu-
 *The Coagulation of the Blood.  F. P. Henry, Archives of
Medicine, December, 1884. 
8
ally acquires all the properties of a mature red
corpuscle.  His  opponents contend that it is a
red corpuscle deprived of its coloring matter by
the very manipulations used to demonstrate it.
The question is still unsettled.
  The functional power of the blood is depend-
ent upon the number and quality  of  its red
corpuscles.  When a deficiency exists in either
of these respects, the tissues suffer for the  want
of oxygen—the  most important  nutritive  ele-
ment of the body.  When the degree of anaemia
is  slight, it  may be manifested by  symptoms
which are not to be  distinguished from neuras-
thenia in its various forms, except by an  exami-
nation of the blood.  The latter affection often
co-exists  with  a perfectly normal  condition of
the blood.  When  the  anaemia is  of  higher
grade, the want of oxygen—equivalent to want
of breath—may not be experienced except upon
exertion, of which the amount necessary to pro-
duce this  symptom is  in inverse  ratio  to the
degree of anaemia.   In extreme cases,  simply
raising the head from  the recumbent position
will suffice to induce  breathlessness or  even
syncope.   Even  in  such  extreme cases,  the
symptoms alone will not suffice for  diagnosis, 
9
for there are diseases of which the most promi-
nent symptoms are due to irregular distribution
of the blood, a hyperaemia of one vascular dis-
trict necessarily causing a correlative anaemia
of another, while the constitution of the blood
is normal.  The most  conspicuous example of
this condition is furnished by Addison's disease,
in which, owing to vasomotor  paralysis, there
is  great accumulation of  blood  in  the  ab-
dominal vessels and a correlative anaemia of
the brain.   Here,  also,  dyspnoea  arises upon
slight exertion; the  muscles  are weak  and
easily fatigued, and in extreme  cases, during
the frequent exacerbations of the disease, simply
raising the head from the pillow is  sufficient to
induce syncope. Until very recent times, these
symptoms of Addison's disease were ascribed
by the most eminent authorities to a high degree
of anaemia.  It is now established that in such
cases the constitution of  the  blood may be
normal, and that the symptoms are due to its
irregular distribution.   Further instances  are
unnecessary to prove the diagnostic importance
of a proper examination  of the blood.  The
presence of anaemia may be guessed at without
such examination,  and the diagnosis (?)  con- 
10
firmed or rejected by the result of the treatment,
while the patient, in the meantime, may have
been  losing what might have been  saved by
proper methods.  Not only the bare  presence
of anaemia, but its variety and degree,  are to be
ascertained by examining the blood, as well as
its progress under different modes of treatment.
In short, no contribution to the clinical history
of a case of anaemia deserves to be compared
with that derived from  an  examination of the
blood.
         METHODS OF EXAMINATION.
  These  consist in the enumeration of the red
and  white  corpuscles, and the  determination
of the percentage of haemoglobin in the former.
The instruments used for counting the corpus-
cles are all constructed upon the same principle,
the  different modifications being  such  as are
designed to facilitate the rapid counting of the
cells, and the easy reckoning of their percentage
as compared with the standard of health.  A
known quantity of blood is diluted with a known
quantity of fluid,  and in a cell of certain depth
and superficies—the latter indicated by squares
of a certain size ruled upon  an  ocular  micro-
meter, or on the bottom of the cell containing the 
11
blood—the number of corpuscles is  counted.
With these factors—the  depth of the  cell, its
superficies, and the degree of the dilution—the
number of corpuscles in a cubic  millimetre  of
blood, for  instance, is  readily  estimated.  It
is  self evident that the  more  the  blood  is
diluted,  the  easier  is  the  counting  of the
corpuscles, and  the  longer  the subsequent
calculation.   The  chief  instruments  in  use
for  counting  the blood  corpuscles   are the
compte-globules  of  M.  Malassez,  for a de-
scription of  which see  Comptes  Rendus de
L Academie  des   Sciences,  Dec,  1872,  also
These  de  Paris, 1873;   the  hematimetre  of
MM.  Hayem and Nachet, described in the
Comptes  Rendus  de L'Academie  des Sciences,
26 Avril, 1875!  and the haemacytometer  of
Dr. Gowers, of London.
  The different  instruments  for  counting the
blood corpuscles  may be used in  combination.
Thus, in  many of my own observations, I have
used Gowers' pipettes with  Hayem and Nachet's
cell and eye-piece.  Thoma and Zeiss {Her-
mann's Handbuch der Physiologie, IV, Bd. I),
also, have constructed an  apparatus composed
of the pipette  used with  Malassez' instrument, 
12
known as the mixer [inelangeur) of Potain, and
a cell similar to that of Gawers.   The instru-
ments of Gowers and Zeiss are superior to the
others  mentioned,  in  that  they may  be  used
with any microscope without adjustment for the
different objectives  employed. The counting is,
however, sometimes rendered very difficult with
Gowers' instrument, on account  of the  large
size  of the squares—y^ of a millimetre.   The
squares in the cell Of Zeiss' instrument are only
^5 of a millimetre, rendering the counting a very
easy task.   Until quite recent times, it was sup-
posed that the  quality of the blood could be
accurately determined by counting its  corpus-
cles.  If these were found below the standard—
5,000,000 per cubic millimetre—anaemia  was
supposed to exist; while, on the other hand,  if
above this  standard, anaemia was confidently
declared to be absent.   It was apparently taken
for granted that the red blood corpuscle was a
constant quantity, a unit, containing invariably
the same amount of haemoglobin.  It  is  now
thoroughly  established  that the  amount of.
haemoglobin in two red corpuscles, from differ-
ent individuals, may vary as much as 50 per
cent., so that the mere number of the corpuscles 
13
does not afford an infallible proof of the pres-
ence or  absence  of anaemia.   When  the cor-
puscles are decidedly below the normal average,
anaemia, of  course, can be determined by a
mere  count, but even  here its  degree can
only be  accurately  estimated by  determining
the percentage of haemoglobin, the reduction
of which is usually greater than that  of the
number  of the corpuscles.  It is,  however,  in
those  cases  of anaemia in  which  the number
of the corpuscles is  normal, or  even greater
than normal, that the  superiority of the haemo-
globin test is  unmistakably manifested.   The
writer  agrees with Hayem,  that, if one  had  to
choose, in  cases of this sort, between the two
methods, the color test would undoubtedly be
preferred.*
  The principal point to be determined in an
examination of the blood is the functional value
of the red blood corpuscles, which bears a direct
ratio to  the amount  of haemoglobin  in each.
 * " Si dans les cas de ce genre, cas d'ailleurs extremement com-
muns, on voulait s'en tenir a l'une des deux methodes d'examen
du sang, c'est done sans hesitation au procede chromometrique
qu'il faudrait donner la preference."  Recherches sur I'anat.
norm, et path, du sang. Paris, 1878. 
14
As a rule, when the number of blood corpuscles
is normal, the amount of haemoglobin is also
normal, or  nearly so, but, and  this fact deter-
mines the value of a color test, there are numer-
ous exceptions to this rule.   Thus, Baxter and
Willcocks found 6,600,000 corpuscles per cubic
millimetre, in a case of typhoid fever, but they
contained only 45 per cent, of the normal quan-
tity of haemoglobin,  making their functional
value equal to that of 2,970,000 normal corpus-
cles ; so  that,  in  spite of the high figures, the
degree of anaemia was great.
  Instruments for estimating the percentage of
haemoglobin  have been devised  by Hayem,
Malassez and Gowers, of which the most simple
is the globinometer of Dr. Gowers.  I have used
this apparatus with  much  satisfaction.  It is
light,  compact, and  easily manipulated.  The
words of its inventor  are equally applicable to
the instruments of Hayem and Malassez. " The
instrument  is  only expected to yield approxi-
mate results,  accurate within two or three  per
cent.   It has, however, been found  of much
utility in  clinical observations."
  From these introductory remarks, the import-
ance, for clinical  purposes, of a proper exami- 
15
nation of the blood is manifest.   It is a signifi-
cant fact that those who, in the course of their
practice, make  frequent  examinations of the
blood, encounter cases of disease never met
with by others, with perhaps much greater op-
portunities for observation  ; but no more so than
that the oculist has become able, by improved
clinical methods, to classify cases  formerly
vaguely known  as  "amaurosis," into  retinitis,
choroiditis, atrophy of optic nerve, separation of
retina, glaucoma, etc.  The wonderful progress
of ophthalmology in recent times has been due
to the  skillful  handling of a small mirror, and
what we know of blood diseases, is due to the
microscope in conjunction with an  apparatus
which is already regarded as  one of its import-
ant " accessories."   We  now proceed to the
consideration of our proper subject, Anaemia.
           AN.EMIA IN GENERAL.
  The term anaemia, signifying an impoverished
state  of the blood, is to be preferred, both on
the grounds of etymology  and euphony, to such
terms  as spanaemia, oligaemia, oligocythaemia,
which have been introduced at various times
on  the plea of greater accuracy.  It has, be-
sides,  the great  advantage of  possessing  its 
16
exact equivalent in the French and  German
languages—" anemie" and " anamie."  All the
different varieties of anaemia are characterized
by a diminution of the  number or value of the
red blood corpuscles ; that is to say, of the nor-
mal amount  of haemoglobin.  From  a clinical
point of view, this is the primary and essential
morbid condition.  It is supposed and argued
that this reduction  in the amount of haemoglo-
bin is preceded by a reduction in the amount
of the plasmatic albuminates ; but this question
is quite as obscure as that concerning the pre-
albuminuric stage of Bright's disease. Anaemia
is not a  neurosis or a functional disorder, as one
might suppose, from the loose manner in which
the term is  occasionally employed, but a sys-
temic condition dependent upon a lesion which
can be demonstrated with the utmost precision.
  There are certain predispositions to anaemia
dependent upon sex, age and constitution. The
female sex  is more prone to anaemia than the
male ; and peculiarly so  during the  pregnant
condition, in which, owing to the great demands
upon the blood for the nourishment of the foetus,
anaemia is the rule.  On the other  hand, the
female sex is  more tolerant of anaemia than the 
17
male, which is partly due to the fact that the life
of females is, as a rule, more sedentary.  Many
women go through a long life without any par-
ticular ailment, but are known to possess what
is termed a  delicate constitution.  Being for-
tunately free from  any constitutional vice, no
organic disorder develops; nevertheless they are
chronic  invalids.   They are usually treated
with excessive consideration by friends and rela-
tives  of their own  sex,  and regarded  by  the
average practitioner as lucrative humbugs. The
fact is, that such women are suffering—if such a
term may be applied to a condition which brings
with it so great freedom from responsibility—from
a light grade of chronic anaemia. It is astonishing
upon what a small amount of food such persons
support a long existence ; but it is to be observed
that if the income  is small the output is still
smaller.  Many such persons play the  role of
amiable drones in  the hive of busy workers.
They do not repine at their  lot, preferring to
bear those ills they have rather than fly to others
(the responsibilities  of health) that they know
not of.
  The predisposing influence of  age is most
marked during youth and advanced life.  The
      B 
is
demands of growth during adolescence render
the equilibrium of the blood peculiarly unstable.
This, also, is more marked in females, in whom
the evolution of  the sexual system is, as a rule,
attended with more systemic perturbation.
  Anaemia  should,  undoubtedly, be  classed
among the tissue changes known to  the histolo-
gist  as  "senile;" indeed, there is excellent
ground  for believing that it  is at the root of
those which are most  suddenly  disastrous, to
wit,  the degenerations of  the  walls of small
blood vessels.   During the  inevitable  period
known  as  the " decline of life,"  the system is
especially intolerant of nutritive  losses.  The
recuperative power  of the blood is impaired.
It  is just  at this period, also, that the diseases
attended with such losses are most prevalent;
among  which  are  to be  reckoned  chronic
catarrhs of mucous  surfaces, such as the pul-
monary and vesical; hemorrhoids, ulcers, etc.
  Anaemia may  be congenital.  In  1883, while
examining the blood of several new-born chil-
dren at the Maternity  Hospital, I encountered
the following case :—
  " Case .3.—Mary  C------, born  5.20 a.m.,
November 5th.   Count made 2.30 p.m., Novem- 
19
ber 6th.   Child weighed six and three-fourths
pounds at birth ; labor natural.  Number of red
corpuscles per cubic millimetre, 3,625,000; pro-
portion of white  cells to red, 1 to 145.   This
case was undoubtedly one of congenital anaemia.
The child's  only appearance of malnutrition
was a shriveled state of the integuments of the
feet, and a less rosy color of the skin than normal.
Foranew-born child, it was decidedly pale. This
shriveled  state of the  skin emphatically nega-
tives the idea of a relative anaemia from excess
of fluid.   The blood was probably deficient in
quantity  (oligaemia)  as  well  as defective  in
quality (oligocythaemia).   There was   also  a
decided increase  in the  number of the white
cells.   Careful  inquiry proved that  there had
been  no hemorrhage from the cord.   As pos-
sibly bearing upon the congenital imperfection
of this child, I may mention the fact  that the
parents were themselves  immature—the father
being seventeen, and the mother eighteen years
old."*  It is possible, also, that the case may
have been one of congenital syphilis.

  * See paper entitled "A Contribution to the  Study of Icterus
Neonatorum,"  by  Frederick P. Henry, m.d.  Archives  of
Medicine, October, 1883. 
20
  The third cause, above mentioned, as predis-
posing to anaemia, is constitution.   No better
proof of  the existence of such a tendency can
be brought forward than the report of the above
case of congenital anaemia. An extended series
of examinations would probably show that  such
congenital deficiencies  in the composition of
the blood are by no means uncommon.   Cer-
tainly, the widest differences of external appear-
ance are presented by the new-born, from the
pale, puny sickling of  five or six  pounds, to
the rosy, vigorous child weighing from ten to
twelve.   With proper care, the puny child may
thrive and grow, perhaps, too rapidly, and pre-
sent every appearance  of health, but in  after
life,  under circumstances to  which  its  more
vigorous  contemporary would  rise superior, the
innate tendency to anaemia will manifest itself.
Precisely similar facts are observed with refer-
ence to the other tissues of the body.  One in-
dividual will not only retain his weight, but grow
fat  upon a diet which another would regard as
but little  removed from starvation.
       EXCITING CAUSES  OF  ANAEMIA.
  It is  hard to draw  a sharp  line between the
predisposing  and exciting causes  of anaemia. 
21
To the writer it seems proper to include among
the latter such causes as are equally operative
in either sex and at all periods of life; but in
such a division no  allowance is made  for the
wide differences in individual power of resist-
ance.
  A cause will excite anaemia in an individual
with an innate tendency to the disease ; while
in another, devoid of such tendency, it will not
do so, unless long  continued or  frequently re-
peated. In the former the cause deserves to be
called exciting ; in  the latter its action is more
closely allied to that of the causes called predis-
posing.   Bearing  this  in mind,  the exciting
causes of anaemia include  hemorrhage and
other pathological discharges, sexual excess, in-
sufficiency of food, light or air (bad hygiene),
the depressing emotions of grief and anxiety,
fever, and, finally,  whatever interferes with the
digestion, absorption and assimilation of food.
It is not pretended  that this list is complete, for,
as Immermann remarks, " Nearly every mor-
bid process, when  it occurs in a severe form, is
sooner or later followed by anaemia."  It would
be tedious to enter  at length into even the chief
exciting causes of anaemia ; but two, which  are 
22
the most  frequently encountered  in medical
practice, deserve  more than  a passing notice.
These are hemorrhage and fever.  Experiments
of Vierordt upon the lower animals—dog, rabbit,
guinea pig—show that death  ensues  promptly,
when, after bleeding, the red corpuscles are re-
duced about fifty per cent.  Later observations
show  that these figures  are not applicable  to
human beings, whose powers  of resisting hem-
orrhage are very much greater.  For example,
Behier (quoted by Laache) reported the case of
a woman  whose  blood,  after a metrorrhagia,
contained but 19 per cent, of  the normal num-
ber of red corpuscles ; having, theretofore, suf-
fered  a reduction of 81 per cent.  The woman
recovered after transfusion.  Laache examined
the blood of five previously healthy women
who had suffered from profuse hemorrhage, and
found the red  corpuscles reduced respectively
37, 61, 62, 64 and 68 per cent.  In three  of the
cases  there was complete restitutio ad integrum,
without transfusion ; in one, death occurred from
an intercurrent disease, septicaemia; and in the
remaining case, improvement  was progressing
at the time of the report.  It must be borne  in
mind, however, that  the result of a blood ex- 
23
amination after hemorrhage, depends upon the
time at which such examination is made.  It is
self-evident  that, if from a quantity of blood
outside the body three-fourths be removed, and
a sample of  the remaining fourth be examined,
its centesimal composition will be the same as
that of a sample  taken  from  the whole mass.
So, also, if the blood in the living vessels be ex-
amined immediately after a profuse hemorrhage,
its composition will closely resemble that of the
entire volume of blood before the hemorrhage.
It will not be identical with it, however, for dur-
ing the progress  of a hemorrhage, the lymph,
the tissue juices, and any ingested fluids,  are
rapidly taken up by the blood  vessels to re-
store the blood volume ;  so that, as Immermann
remarks, the immediate  effect  of  a  profuse
hemorrhage is a " complex dyscrasia, made up
of hypalbuminosis, leucocytosis and oligocy-
thaemia."  It is  no doubt true, in the majority
of cases, that  even  during the  progress  of a
hemorrhage, owing to the diminished vascular
tension, the  " osmotic current of tissue juices "
is strongly  directed  toward the blood vessels;
but I believe there are  cases in which, on ac-
count of the shock to the system produced by 
21
the sudden escape of a large amount of blood,
this current is extremely feeble, or even, for a
time, held in abeyance, and in which, therefore,
an examination of the blood, immediately after
hemorrhage, will show little  or no. difference in
its cellular composition.  The following is a case
in point:—
  On June 6th, 1885,1 examined the blood of a
woman, Mary L.,  aet. thirty-two, who,  during
the preceding four weeks, had suffered from con-
stant metrorrhagia,  which,  on two occasions,
had  been quite  profuse.  I  only succeeded at
last in  stopping the hemorrhagia by the intra-
uterine application of Monsell's solution.  On
June 5th  there was  still some slight  oozing,
which had entirely ceased by the  6th, the day
on which  the examination was made.  Number
of red corpuscles, per cubic millimetre, 4,600,-
000.   Proportion  of white  cells to red, 1  to
460.
   " As far as the number of red corpuscles per
cubic millimetre is concerned (I quote from my
note book), and the  proportion of white to red,
the blood may be considered absolutely normal,
but  the  woman  is  greatly  prostrated, with
blanched skin and mucous membranes.  The 
25
volume of her blood is evidently greatly dimin-
ished."
  As studies of the  centesimal cellular compo-
sition of the blood after hemorrhage,  Laache's
cases are defective, as  he himself admits, on
account of the time between  the hemorrhage
and the first examinations.  These were  made,
respectively, in Case I, on the 20th day after the
hemorrhage; in Case  II, on the 21st; in Case
III, on the 6th; and  in  Cases IV and  V, on
the 5th.
  The  anaemia of  fever offers certain peculi-
arities, to which I have  called  attention in an
article  in The Polyclinic for September 15th,
1885, entitled "The  Latent Anaemia of Typhoid
Fever."  These are, in  part, dependent upon
the loss of  water sustained by the system in all
febrile  affections,  and particularly in  typhoid,
owing  to its long duration and intestinal com-
plications.   In  typhoid  fever, which  may be
taken as a type, notwithstanding the evidences
of an impoverished  state of the blood, afforded
by the profound adynamia and the muscular
tremors, an examination during the height  of
the disease will show, at least, a normal number
of red  corpuscles.   The blood taken from the 
20
finger is of a dark  venous hue, does not flow
readily  on puncture,  and is evidently  inspis-
sated.   The condition is precisely the reverse
of that which obtains  after hemorrhage, which
is  a point of some  interest, since it has been
held, by at  least one eminent authority, that
a moderate  hemorrhage during the course of
typhoid fever is not to be dreaded as a compli-
cation.  This clinical  fact, if it be one, may be
explained by the tendency  of the blood, after
hemorrhage, to regain its former volume by the
imbibition of water.   The therapeutical deduc-
tion is to supply fever  patients  abundantly with
water, as was so  strongly advocated by the late
Dr. J. Forsyth Meigs.
  Although  the  number of red corpuscles in a
cubic  millimetre of blood may  be normal in
typhoid fever, their value  is decidedly below
par.  They  are  deficient  in haemoglobin, so
much so, that six million corpuscles may have
only the functional power of three million.
  In one form of fever, the malarial, recent in-
vestigations tend to show that a micro-organism
may be directly active  in  destroying  the  red
corpuscles.  These  organisms, if such they be,
were beautifully demonstrated by Dr. Council- 
27
man, of Baltimore, at the recent meeting of the
American Association of Physicians.   They oc-
cupy the interior of the red corpuscles, and are
apparently capable of distinct amoeboid move-
ments.  That some agency destructive of the
red corpuscles is operative in  certain cases of
malarial  fever is  proved by the occurrence of
haemoglobinuria as a symptom, which latter is
but itself the sequence of a preceding haemoglo-
binaemia.  The blood corpuscles are destroyed
while circulating in the vessels.

           SYMPTOMS OF AN/EMIA.
  It  is customary for medical writers to describe
the immediate effects of the  sudden  escape of
blood from the vessels as typical of what they
call acute anaemia;  but this, in my opinion, is
a mistake.  As I have elsewhere  said:  " The
symptoms  of acute loss of blood, and its fre-
quently fatal  termination when not more than
one-half  the normal amount has been lost, are
due to sudden ischaemia of the nerve centres."
Anaemia  undoubtedly exists, but is not the cause
of the  immediate  symptoms  of hemorrhage.
These are  due to a disorder of the circulation,
which may be precisely imitated by the appli- 
28
cation of Junod's boot to one of the lower ex-
tremities.
  The  remote effects of a hemorrhage, that is
to say, the condition  of the  patient when  the
nervous system  has recovered  from its shock
and the circulation has regained its equilibrium,
may be taken as typical of acute anaemia.   The
chief of these are pallor of skin and mucous
membranes, muscular weakness, vertigo or syn-
cope, on exertion, or even on assuming the  up-
right position, and a  small, soft, frequent and
excitable  pulse.  In  addition,  there is thirst,
anorexia,  or an  appetite that is irregular and
fanciful.   The digestion is feeble and readily
disordered.  There is a prevailing sense of cold,
and yet  on slight exertion  the skin becomes
flushed and perspiration breaks out.   The tem-
per is  apt to be peevish and irritable, and the
normal control  of the emotions is impaired.
While  the temperature, upon the whole, is low-
ered, irregular pyrexia, to which the term " an-
aemic fever" has  been applied, is  commonly
observed in the severest forms of anaemia.  The
cause of this fever has given rise to much  dis-
cussion, and the explanation offered by Immer-
mann  seems to be the most plausible.   It is 
29
that, owing to the extreme reduction of the nu-
tritive properties of the blood, the tissues suffer
to such an extent as actually to undergo a spon-
taneous decay or necrobiosis, which is attended
with the evolution of heat, as is always the case
"when chemical compounds of a more stable
kind are generated from such as are less stable."
  Haemic,  systolic,  cardiac  murmurs,  and  a
musical murmur (bruit de diable) in the jugular
veins, are among the physical  signs.  In high
degrees of anaemia  there is  great emaciation,
which is generally masked by oedema.  Hem-
orrhages from mucous surfaces, particularly in
the form  of epistaxis, and  into  the retina, are
of common occurrence.  A fatal termination is
generally ushered in by a mild form of delirium,
which may be for days preceded by  a condition
of lethargy, from which  the patient is readily
roused to full consciousness, but relapses into
the lethargic state as soon as the  effort to attract
his attention  is abandoned.   The last remarks
are only  applicable to  certain  fatal  forms of
anaemia into which there is reason to believe an
anaemia  simplex may sometimes be converted.
If an anaemia of high degree, whether it origi-
nate in hemorrhage, fever, or what not, becomes 
30
chronic, all the organs of the body, and among
them, of course, those concerned in blood mak-
ing, will suffer from malnutrition, so that a con-
dition which was at first what is  termed func-
tional, may eventually become organic ; that is
to say, dependent upon  lesions to which it has
itself given rise.

         anatomical characters.
  The anatomical characters dependent upon
a marked and long-continued deficiency of red
corpuscles, are dryness and translucency of the
tissues and fatty degeneration of  the heart, in-
tima of the arteries, renal and  gastric epithelia,
and the hepatic cells. In the heart, the papillary
muscles are chiefly affected, especially those of
the left ventricle, and the morbid change may
be detected by the naked eye in the  form  of
minute,  yellowish streaks, which have been
called "tabby mottling," or  "tabby-cat stria-
tion."  The retinal hemorrhages are dependent
upon degeneration of the vessel  walls and, in
one form of anaemia, upon this, in connection
with a plugging of the vessel affected, with white
blood corpuscles.  The  blood is seen to be less
than  normal  in quantity and of a lighter color 
31
 than natural.  In well-marked cases, it is of a
 light pink color, resembling water in which beef
 has been washed, and the hue which it imparts
 to  linen is sometimes  a pale  yellowish pink,
 which would hardly be recognized as a blood
 stain.  Notwithstanding the  deficiency of red
 corpuscles, and the consequent pale tint of the
 blood, the muscles, even in the highest degrees
 of anaemia, are often found of a deep red color,
 and the adipose tissue of a rich yellow.

                 diagnosis.
  The lighter grades of anaemia merge imper-
 ceptibly into health.  In city  residents, even of
 the well-to-do classes,  whose occupation  is at-
 tended with considerable mental work and its
 inevitable anxiety, anaemia is  the  rule rather
 than the exception. A number of corpuscles, not
 below 5,000,000 per cubic millimetre, of which
 the richness in haemoglobin,  as determined by
 Gowers' haemoglobinometer, does not fall below
 90 per cent., may be considered normal.  This
being understood, the lightest grade of anaemia
would be expressed by the following formula:—
N. (number of red corpuscles per cubic m.) = 100
 H. (percentage  of haemoglobin) .   .  .  =.80
V. (value of each corpuscle)  .  .   .  .  =x% 
32
  An individual whose blood condition would
be expressed by these figures, might show little
or no departure from health, and be aware of
none.  I have several times found such figures
in young men  whose blood I have examined
for the purpose of comparing one counting in-
strument with another.  In the above example,
N. is normal, say 5,000,000, but these 5,000,000
corpuscles possess only four-fifths the normal
percentage of haemoglobin, and are, therefore,
functionally equal to 4,000,000 normal corpus-
cles.
  Anaemia, as a rule, is not clinically appreciable
until the haemoglobin represents between three
and four million corpuscles per cubic m.   The
actual number of red corpucles may be five, or
even  six, million per cubic m., but their real
value is sixty, or even fifty, per cent, of the
normal.  This degree of anaemia is attended by
both signs and symptoms, such as pallor, a ten-
dency to vertigo, flushing of the face,  perhaps
tinnitus  aurium,  muscular  fatigue on  slight
exertion, backache,  irregular appetite, and  a
capricious,  captious temper.  Such a condition
might be merely functional, or secondary to the
early stage  of some  organic affection,  such as 
33
Bright's disease,  diabetes mellitus, carcinoma,
phthisis, etc.
  The next grade of anaemia is that in which
the real value of  the corpuscles is between two
and three millions.   In this degree, the percent-
age of haemoglobin may be much greater than
in the preceding,  owing to the fact that now the
corpuscles  are decidedly  reduced in number.
It is a familiar fact to all students  of blood
diseases that, as  the number of corpuscles di-
minishes, the percentage  of haemoglobin  in-
creases, until in the severest forms of anaemia
—those termed pernicious—it may equal or ex-
ceed, even  double, the percentage  of red cor-
puscles.  A reduction of both  number and value
of red corpuscles is much  graver than a mere
diminution  of value.  A  number  as low  as
3,000,000 generally indicates  a serious state of
affairs, and may depend upon a more advanced
stage of one of the diseases  above  mentioned,
or upon  one  or  other of  the  diseases  of  the
blood-making organs, to be considered later.
  The  highest grades of anaemia are those in
which the real value of the  corpuscles varies
between  500,000  and 2,000,000 per  cubic m.
Such  figures are generally the expression of
      c 
34
diseases of the blood-making organs—spleen,
lymph glands, bone  marrow—or of that form
of "anczmatosis" to which the term pernicious
has been justly applied.   An apparent paradox
is  met with in these intense forms of anaemia,
namely, that 500,000 corpuscles may contain as
much haemoglobin as is usually found  in one
million.  When this is the case, it is due to the
fact that the average diameter of the corpuscles
is decidedly above the  normal.  This increase
in size may possibly be a conservative provision
on the part of nature, but the fact remains that
increased  size and altered shape (poikilocytosis)
of the red corpuscles must  be regarded as of
very grave significance.  An average diminu-
tion in the  size of the corpuscles  is generally
combined with an increase  in their number, a
set of conditions commonly observed in that
form of anaemia called chlorosis.

                 prognosis.
  The prognosis of anaemia in general has been
sufficiently hinted at in the preceding remarks ;
but it  may be well to emphasize the fact that
an anaemia per se is never grave until distinct
anatomical alterations in the red corpuscles— 
35
alterations of size and shape—are manifested.
The prognosis of secondary anaemias is involved
with that of  the primary disease.

    treatment of anemia in general.
  On  account  of  the general prevalence  of
Anaemia,  its preventive  treatment  is  of the
utmost importance.   The great majority of in-
dividuals  who are " run down " in health,  or
suffering from  "nervous exhaustion," which
they attribute to overwork, are simply, as before
said, more or less anaemic.  Overwork is the
unfortunate  scapegoat whose  erratic conduct
renders him an easy prey to both  physician
and patient.   Work may be rather regarded as
a raw, nutritive material, which is  usually pre-
pared and served in an underdone condition.
There  may  be  exceptional  cases  in  which
anaemia is justly attributed to  overwork alone,
but the writer has never seen one.   There is a
careless way of regarding this  matter which
leads to inaccurate statements.  For instance,
if the hours of work encroach upon those of
sleep, it is the want  of  sleep,  as much  as the
excess of work, that is to blame  for the result-
ing anaemia.  If the irrational worker neither 
36
takes the time to eat or digest his meals, his
anaemia is due to inanition or indigestion.  If
he finds, or imagines, that the steady use  of
tobacco,  coffee and alcohol is helpful in  the
kind of work he is performing, it is just possible
that his habits are  alone to blame for his im-
paired  physical state.
  As this is  not a treatise on  hygiene, I  shall
not stop to  indicate the amounts of food, air,
exercise  and  sleep  essential  to  preserve  the
health  of the  average man, woman or child;
but I cannot refrain from pausing to condemn
a prevalent error.  There appears to be a wide-
spread delusion in the minds of young men that
muscular strength and bodily health are synony-
mous terms.  This is true, indeed, but only to
the extent that a certain  amount of muscular
strength  coincides with  the healthy condition.
There  is a limit in each  individual—a Rubicon
—the very attempt to cross which is  attended
with danger.  The story of the man who began
by lifting the calf, and continuing to do so each
day, ended by lifting the cow, is  one of those
plausible lies which  only serve to enhance the
beauty of truth by showing how a germ of the
latter may  give an  air of vraisemblance to a 
37
tissue of falsehood.  It is a pitiful sight, relieved
only by its absurdity, that of a young, slender
stripling exhausting himself in vain efforts to
become  an  "athlete."   Out-door  sports  are
excellent for the growing boy, but heavy gym-
nastics should be reserved, as a rule, for those
who have attained their full growth. The boy
will defeat his object of becoming a strong man
by practicing them too early.  Let him possess
his soul in patience.  As the fisherman says,
in La Fontaine's fable :—
         " Petit poisson deviendra grand,
          Pourvu que Dieu lui prete vie."

  The curative treatment  of a  case  of anaemia
is, in part, determined by its causes, and includes
the control of hemorrhage  and other patho-
logical discharges; the removal from an unfav-
orable hygienic environment; the administration
of a proper amount of nutritious food, and the
suppression  of causes which interfere with its
digestion and assimilation.  In many inveterate
cases, in which cure is still possible, this result
cannot   be   attained without  weeks, perhaps
months, of persevering treatment.  A complete
control  of the  patient is essential, and to  this 
38
 end, the seclusion insisted  upon by Dr. Weir
 Mitchell is of great  importance,  for by it an
 important obstacle to recovery is at once re-
 moved, to wit, the  demoralizing sympathy of
 injudicious friends.  Excellent results have been
 accomplished by the means so  judiciously em-
 ployed  by Dr. Mitchell, namely, rest, seclusion
 and passive  exercise in combination with  the
 diet and medication adapted to the peculiar
 exigencies  of the case.  This method of cure
 has been elaborately explained by Dr. Mitchell
 in his well-known work, entitled,  " Fat and
 Blood," and is doubtless familiar to the medical
 men of this country.   I have seen a number of
 cases of chronic  anaemia whose  treatment by
 this method has been attended with the happiest
 results.   I have also  seen it fail, as is to be ex-
 pected where everything fails,  namely, in  the
 secondary anaemia of malignant  disease, and
 also in  certain advanced cases  of pernicious
 anaemia, in which there were marked alterations
 in the size and shape of the red corpuscles, as
 well as extreme diminution  of their number.
  The advantages to be derived from a thorough
employment of the so-called rest cure are with-
in the reach of few, and in the majority of cases 
39
our main reliance  is on drugs.  The chief of
these are iron, arsenic, the mineral acids and
cod-liver oil.  Hayem also reports the success-
ful  employment  of ferrocyanide of potassium
in cases of decided anaemia. The preparations
of iron  are so  numerous that, supposing them
to be of equal value, one might well be at a loss
to select from among them.  This, however, is
by no means the  case, and I will, therefore, in-
dicate those which I consider the best.   In  pill
form nothing has given me more satisfaction
than the formula  of Blaud :—

  R.   Ferri sulphatis,
       Potassii carbonatis,   aa    gr. iss.    M.
  Sic—One, or more, after each meal.
  To obtain the  best effects of a ferruginous
preparation, it  is  often  necessary to give it in
large doses, and  the  above is  no exception to
this rule.  It may be pushed,  if well borne, to
the  extent  of three pills thrice  daily.   The lac-
tate, the pyrophosphate, the malate and Que-
venne's powder,  are  all excellent preparations
of iron.  Strychnia, quinia and arsenic may be
advantageously combined with the iron.  The
latter preparation is best given in the  form of 
40
Fowler's solution.  In addition to its specific
action upon  the  skin, arsenic  has for a long
time been recognized as  possessing a general
beneficial action  in  certain states of impaired
nutrition,  which  had caused it to be classed
among  the  agents  known as  " eutrophic."
There is no doubt that much, if not the whole,
of this favorable effect is  due  to the increased
amount of haemoglobin in  the  blood,  which
results from its administration.  Arsenic is spe-
cially indicated in anaemias of  malarial origin,
although its use is by no means limited to these
forms.
  The  treatment of  secondary  anaemias  is
largely influenced by the nature of the primary
affection.   As  a  general  rule, arsenic will  be
found of  service  in  those forms  of secondary
anaemia in which there is a  state  of congestion
or catarrh of the gastro-intestinal mucous mem-
brane.  Osier reports good  results from  its use
in the anaemia of heart disease, the " cachexie
cardiaque" of French writers.  In the  causa-
tion of this form of anaemia, the obstacle to ab-
sorption presented by the engorgement  of the
gastro-intestinal veins is an important factor.
  In cases with a syphilitic history, the mercuric 
41
chloride may be usefully administered with iron,
as in the following formula:—
  R.   Hydrarg. chlorid. corrosiv.,  gr.j
       Tinct. ferri. chlorid.,       3 ij
       Glycerin.,                g ss
       Aquse,      q.s. ad.       giij.      M.
  SiG.—One drachm  after each meal.  The dose
may be  gradually increased to  two drachms thrice
daily.

  The ferrocyanide of potassium recommended
by Hayem is worthy of trial, on account of its
endorsement by so  distinguished an authority
on the physiology and  pathology of the blood.
He begins by giving one gramme (about gr. xv)
daily, in two powders, and gradually increases
the dose until six grammes, in six powders, are
given.
  Transfusion is a measure which  has  been so
often adopted as  a  dernier  ressort that it has
fallen  into discredit.   If any benefit is to be
derived from transfusion, it  is  certainly not
when the patient is  moribund.  After the sud-
den escape  of  a large amount of blood, the
natural process  of restoration may be best imi-
tated by the  injection into a vein of a normal 
42
saline  solution  (0.6   per   cent.  NaCl.),  the
amount of which must be  determined by the
effects  upon  the patient; or the  following for-
mula of Hayem for intra-venous injection in
cholera, may be employed :—

  R.  Distilled water,           1 litre
       Sodium chloride,  pure,     5 grammes
       Sodium sulphate,  pure,     10 grammes.   M.
  Sig.—Filter and inject slowly at a temperature of
380 C. (100.40 F.)

  When the  object of  transfusion is  not so
much to overcome the  effects of sudden ischae-
mia of the nerve centres as to introduce a gradual
improvement in the patient's nutrition, defibrin-
ated blood should be employed.
  It has been pointed out that when the respira-
tion is greatly embarrassed, the injection  into
the vessels of an additional  amount of reduced
haemoglobin,  such  as  exists in venous blood,
may only make matters worse by adding to this
embarrassment, and so accelerate a fatal end-
ing. In such cases the  blood to be transfused
should be taken from an artery.  Quite recent-
ly the injection of defibrinated blood into the
peritoneal cavity and  into   the  subcutaneous 
                     43

connective tissue has  been practiced with ap-
parent benefit.  The dangers attendant upon
the transfusion of heterogeneous blood are well
known.  It should  never be used.  Milk  has
been  transfused successfully in  a few rare in-
stances, but for this purpose is greatly inferior
to defibrinated  blood.  It is apt to occlude the
vessels, many of its globules being much larger
than the largest white corpuscles.  If used,  it
should be boiled, in order to destroy the bacteria
which are almost sure to be present.
           varieties of anemia.
   Anaemias are properly classified with refer-
ence to their origin.  The nutritive fund of the
blood is continually drawn upon in the processes
of nutrition, and if the demands  are inordinate,
as in fever and hemorrhage, the resulting anae-
mia may be justly  ascribed  to  undue  waste.
Under this head a  large  number of anaemic
conditions might be grouped.  A large propor-
tion of the remainder might, with equal pro-
priety, be attributed to  inadequate  supply  of
nutritive materials, due either to absolute want
of proper food, or to  its imperfect digestion  and
absorption.  There would still remain a number
of cases in which both of these causative factors 
44
are so intimately combined that it is impossible
to decide which of them  deserves the  greater
etiological importance.  A division based upon
such physiological data as  above pointed out,
although desirable, is, with our present  knowl-
edge, altogether  inadequate.  Like  so many
classifications in other departments of medicine,
it is not ample enough to cover our ignorance
of the  subject.   In a previous contribution* to
the literature of anaemia, I advocated a division
of its different forms into essential and symp-
tomatic, and gave the following explanation of
my reasons for so doing:—
  "By  essential anaemia, I mean those forms
of the affection that are associated with  disease
of the cytogenic organs, or with congenital mal-
formations of the vascular system, namely, the
lymphatic, splenic and medullary anaemiae, and
chlorosis; and by symptomatic  anaemia, those
forms of the disease associated  with  affections
of non-cytogenic organs  which interfere with
nutrition, such  as febrile  anaemia, the anaemia
of phthisis, cancer, Bright's disease, the anaemia
of heart disease—cachexie cardiaque of Andral
—the anaemia of lead poisoning and of inani-
* Cartwright, Essay, 1881. 
45
tion.  Malarial and syphilitic anaemia occupy
the border line between the two classes.  When
recent and dependent upon an acute attack,
they may come under the head of  febrile anae-
mia,  but when  chronic,  they are frequently
essential, the one generally of the splenic, the
other of the lymphatic, variety.  These afford
interesting  examples  of the conversion of a
symptomatic  into an essential anaemia, and it
is  held by the writer  to be highly probable
that  they are not the only instances of such
conversion."
  The time that  has passed since the above
paragraph  was written  has  only served  to
strengthen the opinions it contains, more espe-
cially that  concerning the  conversion of one
form of anaemia into another.   At present,
however, I  prefer the terms  "primary" and
"secondary"  to  "essential"  and "symptom-
atic," because they are more widely employed
and more  in  accord with our general medical
nomenclature.
   In addition, I am in  favor of a third division,
to include those  forms of anaemia due to the
destructive effect of toxic substances upon the
blood corpuscles, and would suggest for them
the term toxancemia. 
                       46

  Anaemias of parasitic origin are so important
in certain countries (and  perhaps more so in
our own  than we suspect) as to merit separate
classification.
  The following classification is offered, in the
belief that it is one under which all the different
varieties  of  anaemia may  be  appropriately
grouped:—
              i.  primary  anaemias.
    Chlorosis.
    Lymphatic anaemia (Hodgkin's disease).
    Splenic       "
    Leucocythsemia.
    Pernicious anaemia.
           II. secondary anaemias.
    Anaemia of fever.
         "    hemorrhage.
         "    phthisis.
         "    heart disease.
         "    cancer.
         "    syphilis, etc.
              hi. toxan^mias.
    Anaemia of lead poisoning (saturnine anaemia).
         "    arsenic   "
         "    arseniuretted hydrogen poisoning.
         "    phosphorus poisoning.
         "    nitric oxide    " 
47
           IV. PARASITIC anemias.
    Anaemia caused by Anchylostomum duodenale.
       "       "    Bilharzia haematobia.
       "       "    Filaria sanguinis.
       "       "    Plasmodium malarias.

     CHLOROSIS.  ANAEMIA OF PUBERTY.
  With the advent of puberty comes the most
sudden and imperative demand upon the blood
that is  encountered during the normal life his-
tory of the individual, and this  is  superadded
to the  continued demands of growth, which is
most active at this period.  It is, therefore, not
surprising that an anaemic condition is common
at this  time of life; the wonder is that it  is not
the rule.  The developmental impulse of pu-
berty will rouse from their dormant existence
any congenital imperfections of the blood such
as  were described  in  an early part of  this
work.
   A great deal of confusion surrounds the sub-
ject of chlorosis, which is partly due to the fact
that statements made by well-known authorities
in times when the blood was but rarely exam-
ined, have been repeated ever since by writers
upon the subject.  The researches of Johann 
48
Duncan, in  1867 * demonstrated that in chlo-
rosis the red corpuscles may be normal in num-
ber, while their value—the quantity of  haemo-
globin  they  carry — is greatly  reduced.   In
Duncan's cases—three in number—the percent-
age of haemoglobin was 0.3. 0.31  and 0.37, the
normal standard being 1.  While there  can be
no  question  of  the originality  and  value of
Duncan's demonstration that the coloring mat-
ter of the red corpuscles may be reduced with-
out a corresponding diminution of their number,
I am convinced that such a condition is  not pe-
culiar to chlorosis or any other form of anaemia.
In fact, in one of the cases upon which his cele-
brated observations were made there is room
for doubt as regards the diagnosis, owing to the
fact that the patient had a splenic tumor.
  By chemical analysis of the blood, in cases
of chlorosis,  a condition has been  detected
which is thought by some to be pathognomonic.
Becquerel and Rodier, and  Quinquaud  have
found a normal  proportion of albuminates in
the plasma of chlorotic blood, while in the blood
of anaemia in general, they are  said to be di-
  * Sitzungsbericht der K. Acad, der Wissensch.  in Wien.
B. lv, 1867. 
49
minished.  Indeed, the first two observers have
found a condition of hyperalbuminosis.  Im-
mermann, in his excellent article in Ziemssen's
Cyclopaedia, adopts  this as the  distinguishing
trait of chlorosis, which  he regards as an affec-
tion suigeneris, and  deprecates any attempt to
" merge it in the great ocean of anaemia."  He
holds that the blood in this  affection is deficient
in haemoglobin alone  without any corresponding
diminution in the albuminates of  the plasma.
  Quincke, in view of the discrepancies between
his  own examinations of the blood in cases of
chlorosis and those of Duncan, concluded that
there must be at least two kinds  of chlorosis—
the one with a normal number  of corpuscles
deficient in  haemoglobin ;  the  other with a di-
minished number of  corpuscles, which may be
either normal  or deficient with regard to their
haemoglobin.*  Laache has examined the blood
of cases presenting the typical  picture  of chlo-
rosis, and found it normal in every respect. He
  * " Es muss daher verschiedene Chlorose geben, die eine mit
normaler  Zahl aber verringertem Hb-gehalt, die andere mit
verminderung der Zahl derselben wobei  der Hb-gehalt des
einzelnen normal oder ebenfalls vermindert sein kann."—Vir-
chow's Arch., 1872, B. liv., p.537.
      D 
50
proposes for these  anomalous  cases the term,
pseudochlorosis.  He contends that  they are
cases of chlorosis, because their symptoms are
identical with  that affection, and quotes with
approval the following sentence from the thesis
of  Moriez :   " L'hematologiste diagnostiquera
I'anemie et  ne pourra  pas diagnostiquer  la
chlorose; ceci est affaire au clinicien."  I may
say, in passing, that I entirely dissent from this
view of the  subject.  Virchow  has endeavored
to place chlorosis  upon a distinct anatomical
basis by demonstrating, in fatal  cases, an im-
perfect  development of the heart and blood
vessels.  He has found the aorta of a full-grown
woman so small as barely to  admit  the little
finger, and its coats, while preserving their elas-
ticity, were  much  thinner  than normal.    In
addition, degenerative  changes  in the intima
were often  met  with.  With  this  diminished
calibre of the arterial system, the heart may  be
either normal in size, subnormal, or hypertro-
phied.  When it is recalled that the blood vessels
and the red corpuscles are  derived  from the
same  embryonic  layer—the  mesoblast—the
bearing upon the pathology of chlorosis of a
congenital  hypoplasia  of this  portion of the 
51
skeleton becomes manifest. Virchow's doctrine
has not, however, met with general acceptance.
One of the most important functions of the ar-
terial system is its power of adaptation to varying
volumes  of blood, and in chlorosis, to employ
the words  of  Coupland,   "no proof has been
given that the  diminution in  size of the vessels
has not followed upon diminution  in the total
quantity  of blood."  With  reference  to this
subject, Fagge remarks:   "I believe that such
affections are not congenital, but due to  endo-
carditis occurring in childhood.  Thus it seems
to me that the hypoplasia of the aorta, instead
of being itself  a primary defect, is but a second-
ary result  of the valvular lesion.   I am not,
therefore, disposed to attach much value to Vir-
chow's observations as they stand at present."
  From the above remarks, an idea may be
obtained of the obscurity surrounding the sub-
ject of chlorosis from an anatomical and chemi-
cal standpoint.  The same is  true with  regard
to its clinical  history.  The most various con-
ditions of different organs and systems  have
been  described  as more or  less symptomatic
of this affection.  The heart  has  been  found
abnormally small in  some  cases,  abnormally 
52
large in others.   The genital system is some-
times imperfectly developed; at others, its devel-
opment exceeds  the normal limits.  Sometimes
amenorrhoea exists, and may either precede or
follow the anaemic symptoms.  On the other
hand, a chlorotic menorrhagia has been spoken
of.   The  number  of red  corpuscles has been
found normal in  some cases, increased or dimin-
ished in  others.   Immermann's view that the
blood of chlorosis is peculiar in that it is only
deficient in haemoglobin, the plasmatic albu-
minates being undiminished, is not generally
accepted, for "it has not been proved, except
in a few cases of pernicious anaemia, that the
serum albuminates  are  diminished  in other
forms of idiopathic anaemia besides chlorosis."*
With regard to  Laache's  cases of pseudochlo-
rosis, there can be no doubt that the symptoms
were due  to irregular distribution of the blood,
especially to the supra-diaphragmatic  portion
of the trunk.  A blood of good quality, if not
properly distributed, may  give rise to some of
the gravest symptoms of anaemia, such as pallor,
syncope, cardiac palpitation, feeble  pulse, etc.
  * Coupland.  Gulstonian Lectures  on Anaemia.  Lancet,
April  16th, 1881. 
53
This is well  seen in certain cases of Addison's
disease.
  The confusion in which the  subject of chlo-
rosis is involved is due to the persistence in
regarding it as a disease sui generis, distinct
from all other forms of anaemia.  The truth of
the matter appears  to me to be simply this :  At
the time of puberty there is an urgent physio-
logical demand  upon the blood, which is com-
plied with by vigorous individuals without detri-
ment to the organism.  The  ordeal of puberty
is  safely passed.   In  less vigorous,  but still
sound, healthy organisms, a decided  degree of
anaemia, one calling for treatment,  declares
itself  at this  time.  Finally, in those with any
congenital tendency  to anaemia, whether this
may have  been due to  general malnutrition
during intra-uterine life, or to  a  special hypo-
plasia of the vascular system (the  mesoblast),
the anaemia of puberty is intense.  The case is
a typical one of chlorosis.
  The term  chlorosis is  too  convenient to  be
readily abandoned, for under it has been, and
will be, included many sins of diagnosis.  This
is a questionable advantage, and the term should
only be used to  express an anaemia  occurring 
54
at the age of puberty and in the great majority
of cases, in the female sex.
                 DIAGNOSIS.
  The diagnosis of chlorosis is included in that
of anaemia in general.  There is nothing special
with regard to the blood to mark it as a distinct
disorder.  In mild cases there may be a normal
number of blood corpuscles,  and a  reduction
in the  amount of haemoglobin which may  be
but 60, or even 50, per cent, of the normal.   In
severe  cases the number of corpuscles and the
percentage of  haemoglobin  are both reduced.
In the well-marked case  of a young lady aet.
17, whose blood I recently examined, I  found
the following figures :—
No. red corpuscles per cubic millimetre, 2,690,000.
Color (haemoglobin)......32 per cent.
  The  percentage  of red corpuscles (haemic
unit), as compared with the normal (5,000,000),
was  54, so that the value of each corpuscle was
only |f of the normal, making the  2,690,000
corpuscles found equal to  1,594,080 normal
corpuscles.
  The corpuscles were smaller than normal and
perfectly circular in outline.   The white cells 
55
were  not increased.   With  reference to the
mere  number of the red  corpuscles  in  chlo-
rosis,  Hayem gives 3,520,000 as the  mean  of
eighteen counts  (about 70.4 per  cent.),  and
Coupland about  3,000,000, or 60  per cent,  as
the mean in seven cases.   As concerns the size
and shape of the corpuscles, there  are different
statements.   As a rule, they vary considerably
in size, but the average is below  the normal.
This is also the opinion of Hayem and Laache,
while Malassez  considers  the average size  of
the corpuscles to be increased.  This discrep-
ancy may be due to the fact that  in the  more
intense forms, those  approaching pernicious
anaemia  in their symptoms, there  is a greater
number  of  large-sized corpuscles. In perni-
cious  anaemia the  average size of  the corpus-
cles is decidedly above the normal, and  since
this fatal affection is due, in my opinion, rather
to the prolonged operation  of the   ordinary
causes of anaemia than to  one that is  specific,
it is evident that those  cases of chlorosis which
approach the  border line will show a greater
number of large corpuscles  than those further
removed from it.  Chlorosis is to be distin-
guished  from Bright's  disease, especially the 
56
insidious  form so often associated with con-
tracted kidneys,  and from the  early  stage of
phthisis.  The former differential diagnosis is
to be made by careful, perhaps repeated,  exam-
inations of the urine;  the  latter by means of
the thermometer.  According to Peter,  the  sur-
face  temperature  of  the  superior  intercostal
spaces is normal or subnormal in cases of chlo-
rosis, and the same  on both sides ; whereas, it
is elevated on both sides, with a difference be-
tween the two, in latent tuberculosis.  In chlo-
rosis, also, the phosphates  of  the urine  are
below the normal figure, while in early phthisis
phosphaturia  is quite common.  The cardiac
murmurs in chlorosis  should not be too hastily
set down  as  haemic.   An interesting  case in
point is reported by Dr.  T. K. Chambers  (" Re-
newal of Life ")—that of an unmarried  servant,
aet. 25,  with symptoms  of  anaemia so  marked
that the attempt to stand upright caused faint-
ness.  There was pain  in the cardiac region  and
a  loud blowing murmur with the  first sound.
" This blowing murmur was very  audible all
over the cardiac region and up the large vessels
into the neck, but loudest,  and of a  harsher
character  than elsewhere, just at the  level of 
57
the  aortic valves."   Under the use  of Mist.
Ferri Comp. all the  anaemic symptoms  disap-
peared in twenty-one days, although the " car-
diac murmur  remained as loud, if not louder,
and was equally ringing in its tone at the level
of the aortic valves."  There had been no his-
tory of acute rheumatism, and  Chambers con-
cluded—and I think most justly—that the car-
diac lesion was one of arrest of development.
                 PROGNOSIS.
  The prognosis of recent, uncomplicated chlo-
rosis is good.  If of long duration, the nutrition
of the cytogenic organs may have suffered to
such  an extent  that they are incapable of re-
suming their normal functional activity.  The
case is  now inveterate, or pernicious, and its
progress is, as a rule, from bad  to worse.  The
blood corpuscles now resemble those  of the
amphibia in their number, their size, their shape
and their percentage of haemoglobin, and re-
covery is all but hopeless.  Intercurrent febrile
and inflammatory affections are more than usu-
ally dangerous in cases of chlorosis.   The com-
plications to be dreaded in chlorosis are phthisis,
gastric ulcer, endocarditis and chorea.   There
also seems to  be a certain causal relationship 
58
between chlorosis and exophthalmic  goitre—
Graves' disease.  The best test of the  ultimate
prognosis is the immediate  effect  of proper
treatment, the response to which in chlorosis is
remarkably prompt and decided.
                 TREATMENT.
  For the treatment of uncomplicated chlorosis,
we  have a specific in the preparations of iron.
To  show numerically  the effect of  this drug,
I append the  following  figures from  a case
published  by  me in  the  Cartwright  essay,
1881:—
 April  23d, No. red globules per c. mm., 1,870,000
 April 30th,      "     "      "     2,945,000
 May  7th,      "     "      "     3,905,000
 May 19th,      "     "      "     4,315,000
 June 16th,      "     "      "     4,695,000

  " This case affords a remarkable instance of
the effect of iron in  the  treatment of certain
forms of anaemia.  It is  classified under the
head of chlorosis, on account of the menstrual
troubles to which the patient has been  subject
since the period of puberty, the habitual delicacy
of her constitution depending, so far as can be
ascertained, upon a  chronic deficiency in the
blood-making function; and, finally, on account 
59
of the  haemic cardiac  murmurs,  which gradu-
ally  disappeared as the quality  of the blood
improved."   The preparations used were, first,
the reduced iron, which was afterward changed
to the  pyrophosphate.   Blaud's pill, the proto-
chloride of iron in  pill form (Rabuteau's pill),
the lactate and the malate, may all be employed.
There  are many cases in which, owing to digest-
ive troubles, iron cannot be immediately em-
ployed.  The best  method of preparing such
patients for  specific treatment with iron is a
more or less systematic employment of the rest
cure, including massage, passive  exercise, and
a  carefully  regulated,  nutritious  diet.  Before
administering iron,  the physician must be satis-
fied that a cardialgia, if present, is not dependent
upon a gastric ulcer. To effect a cure, iron must
sometimes be given in heroic doses.  Valuable
therapeutic  data may be obtained  by frequent
examinations of the blood during the treatment
of a  case.
            ANAEMIA LYMPHATICA.
   This disease is almost as  rich in synonyms
as in symptoms.  In addition to the title at the
head of this  section, the following terms are
commonly  applied  to   it:  Adenia, Pseudoleu- 
60
kaemia, Malignant  Lymphoma, Lymphaden-
oma, Lymphosarcoma, and Hodgkin's Disease.
These  are far from being equally appropriate ;
but something can be urged in favor of each
one of these terms, in accordance with the point
of view of him who applies it.  Thus, the sur-
geon, having  his attention directed to the ex-
ternal manifestations of the disease, will natu-
rally employ one of the titles ending  in  oma,
while the countrymen  of Hodgkin will  con-
tinue to make use of the one which  associates
with the disease the name of the discoverer.  I
have already written  upon this subject, under
the title " Hodgkin's Disease," with the explan-
ation that "the perplexing nomenclature of this
affection has led the writer to adopt the  term
' Hodgkin's  Disease,'  in  the  belief that it  is
more generally  understood than any of the
other terms  employed."   From the  present
standpoint, that of anaemia, it seems to  me that
the term  Anaemia Lymphatica is  to  be pre-
ferred.  I refer those who may be interested in
investigating the claims of Hodgkin to the dis-
covery of this disease to the Medico-Chirurgical
Transactions, Vol.  xvn, 1832, where it is first
clearly described from a clinical point  of view. 
61
From a purely anatomical standpoint, Malpighi
deserves the honor of having been the first to
call attention to the  pathological combination
of enlargement of the splenic corpuscles which
bear his  name with general hypertrophy of the
lymphatic glands.  This  is  proved by  the fol-
lowing quotation, which was  brought to the
notice of  Dr. Hodgkin by  Mr. G. O. Heming:
" In homine difficilius emergunt (speaking of
the granules in the spleen), si tamen ex morbo
universum glandularum genus turgeat, mani-
festiores redduntur, aucta ipsarum magnitudine,
ut in defuncta  puella observavi,  in  qua. lien
globulis  conspicuis  racematim dispersis totus
scatebat."
  The anatomical features of  anaemia lym-
phatica are hypertrophy, more or less  general,
of  the lymphatic glands ;  hypertrophy of the
spleen, due to  enlargement of its Malpighian
bodies ; the development of adenoid tissue in
various parts  of the body ; a high,  although
usually not extreme, degree of anaemia ; and
the absence of leucocythaemia.  It usually be-
gins as a local, glandular swelling upon the
surface of the  body, which  may remain lim-
ited  for  weeks or  months to  one  lymphatic 
62
group.  We are ignorant of any law governing
the extension of the glandular  enlargement.
At  times  it follows  the course of  the  lymph
stream ; at others, beginning in the neck, axilla
or groin, it will next attack glands in either of
these  situations  on  the  opposite  side.  The
superficial  glands are usually chiefly involved,
especially  those of the  neck and  axilla, but
cases  have been observed in  which  the morbid
process has been limited to the deep lymphatics
of the trunk.   In a  case reported by Osier
{Canada Med. and Surg. Journal,  Feb., 1881)
the retro-peritoneal glands were the only ones
affected.  The  enlargement  is not inflamma-
tory, neither does it cause inflammation in the
surrounding connective tissue.  The individual
enlarged glands are, therefore, freely  movable
upon  each  other, and  not united  into a  dense
mass, as in scrofula.   Their consistence varies.
They  may be soft, almost to the point of fluc-
tuation, or  of nearly cartilaginous  hardness, but
no division of the disease can  be based upon
such differences, for hard  and soft glands may
be present  in the same case at  the  same time.
While the changes  characteristic of scrofula
—chronic inflammation, suppuration and case- 
63
ation—are conspicuous by their absence, there
is no positive antagonism between " lymphad-
enoma"  and  scrofula,  and,  therefore,  such
changes are now and then encountered.  They
may be excited by  traumatism of the super-
ficial tumors.  On section, the  soft  glands are
gray or grayish red, and yield  an abundant
turbid juice, while the hard ones are, on section,
of a yellowish white color, and exude a  thin,
transparent fluid.  Ecchymotic  spots and apo-
plectic extravasations may be  present in both
forms  of  tumor.  Under the microscope, the
difference in consistence of the growths is found
to be owing to the degree of thickening of the
glandular reticulum and septa.  The soft tumors
are due solely  to numerical increase  of the
cells, which differ, for  the  most part, in  no
respect from  normal  lymph  cells, although,
here and  there, larger, darkly granular cells,
with two  or three nuclei, may be met with,
and true giant cells, with ten to twenty nuclei.
The hard tumors present the same appearances,
with more or less  thickening of the glandular
connective tissue.
  The splenic  enlargement,  although  a char-
acteristic feature, is  believed to  be generally 
64
secondary to that of the glands, for cases have
been observed in which, with general involve-
ment of the latter and secondary formations of
adenoid tissue in other organs,  the spleen re-
mained  normal.  The enlargement  of  the
spleen  is mainly due to an hypertrophy of those
masses of adenoid tissue which so closely resem-
ble the lymphatic glands—the Malpighian cor-
puscles.  The spleen, in  this  disease, never
attains the colossal  size it sometimes reaches
in leucocythaemia,  its  long  diameter rarely
exceeding  ten  inches.  The diameter  of  the
hypertrophied Malpighian corpuscles varies from
that of a pin's head to one or two centimetres,
and their white or yellowish color, like  that of
the lymphatic glands, contrasted with the dark
red color of the pulp, gives to the cut surface a
characteristic variegated  appearance.  Adhe-
sions of the capsule of the spleen to neighbor-
ing organs are commonly met with.  The  en-
larged  corpuscles may easily be mistaken for
tubercular  masses,  especially  as,  under  the
microscope, they are seen to contain the same
elements,  namely, small round cells, more or
less altered in appearance, and  giant cells con-
tained  in a reticular  tissue.  The arrangement 
65
of these constituents, however, is, according to
Langhans, different from  that of tubercle.  In
the tubercular nodule  the reticulum  is in the
centre, or in a zone between the periphery and
the centre, while in  the lymphadenoid nodule
the reticulum occupies the periphery, the cells
the centre.
  The infective nature of Anaemia Lymphatica
is shown by the development of adenoid tissue
in organs and tissues of which it is not a normal
constituent, such as  the  liver,  kidneys, lungs,
heart, testicles  and  digestive  tract;  less fre-
quently the bones, skin and nerve centres.  The
metastatic nodules spring  from the connective
tissue of  the organ  ;  in  the  lungs, from the
peribronchial connective  tissue ; in the liver,
from the  capsule of Glisson, etc.  The suppo-
sition that they may  arise  from the  endothelial
cells of  the lymph  spaces has  not yet  been
established.  The microscopic  structure of the
nodules has been most carefully studied in the
liver, and their origin proved to be in the inter-
acinous  tissue,  by the fact that a bile duct
usually  occupies their centre.  Dr.  Burdon-
Sanderson, having  observed  a  thickening of
the walls of the  intra-lobular capillaries and a
      E 
66
vacuolated condition of the liver cells, thinks it
probable that the growth may originate in the
glandular tissue.  Instead of  nodules, a diffuse
leucocytal infiltration of the inter-acinous tissue,
as in incipient cirrhosis, is sometimes observed.
In the lungs, the nodular deposits have been
often mistaken for tubercle.  They invade the
organ from  behind forward, starting from  al-
ready enlarged lymphatic glands.   In the kid-
ney the deposit assumes the form of inter-tubular
streaks. .On the serous  membranes it occurs
in the form of flattened patches, which may be
half an inch in diameter.   Under the influence
of this disease the thymus gland may, although
almost completely atrophied, resume its original
shape and size.  The follicles at the base of the
tongue, the tonsils and the retro-nasal  adenoid
tissue (" pharyngeal tonsil "), may be so greatly
enlarged as  to completely occlude  the posterior
nares.   The  thickening of the intestinal walls
from new formation  of adenoid  tissue  may be
enormous, but it has never been known to cause
stricture.  In a case reported by Dr. Murchison,
the walls  of the duodenum were  from one to
two inches thick, and yet the " intestinal mucous
membrane corresponding to the morbid deposit 
67
 was not ulcerated, and  the calibre of the  gut
 did not appear materially narrowed."   Various
 forms of paralysis may  be due to the deposit
 having its seat in the nerve centres, but such
 cases are exceedingly rare. The blood is dimin-
 ished in quantity and of poor quality.   Macro-
 scopically, it  is  light  colored,  thin and un-
 coagulated  in the heart chambers, or, if coag-
 ula are present, they are quite small.   Careful
 counts of the blood corpuscles have proved that
 the diminution in their number is, as a rule, by no
 means so great as that observed in cases of per-
 nicious anaemia.  In four cases carefully studied
 by Laache the greatest reduction in the number of
 the red corpuscles was 1,830,000 per cubic mil-
 limetre,  the count having been made eleven
 days before the death of the patient.  In a case
 of my own, a boy  of five, with  enormous en-
 largement of the right cervical glands, the num-
 ber of  corpuscles per  cubic  millimetre was
 5,462,000, while the haemoglobin was only sixty
 per cent, of the normal;  so that the functional
 value of the corpuscles was diminished by forty
per cent.  In  a case reported by  Dr.  Richard
Geigel {Deutsches Archiv fur Klinische Medi-
an, Bd. 37, p. 59,  1885), that  of a boy twelve 
68
years old, the right side of whose neck was occu-
pied by a glandular tumor as large as a child's
head, almost daily counts of the  blood corpus-
cles were made from June 7th to July 23d.  The
lowest  count was 960,000, on July 12th.   The
percentage of haemoglobin was never estimated.
  Effusion into the pleural and abdominal cavi-
ties is often  found, and may be due to the irri-
tation caused by growths of adenoid tissue upon
these membranes, or to the pressure of en-
larged  glands upon  the vena azygos  and the
vena portae.  Hydrops lactea may  be  caused
by the  pressure of enlarged glands upon the
thoracic duct.  The bone marrow is very rarely
affected.   Birch-Hirschfeld  knew of but one
case in which this tissue was abnormal.   The
bones  themselves,   especially  the vertebrae,
sternum  and ribs, may be eroded by the pres-
sure of enlarged glands.
  Nature of the Disease.—This is  best under-
stood by comparing it with another disease,
with which,  but  for an examination  of the
blood,  it would  certainly  be  confounded,
namely, leucocythaemia.  Langhans, in view of
the fact that the  principal distinction  between
these two diseases is the absence in the former 
69
of an increase in the number of white corpus-
cles, has  suggested their classification under
one  head, such  as  adenia or lymphadenoma,
with the division into a leukaemic and a non-
leukaemic form.   Dr. H.  C.  Wood  is of  the
opinion that, " clinically, the so-called true and
false leukaemia are  the same, save only in  the
matter of the white  blood corpuscles."  This is
also  the  view of Dr. Wm.  Pepper,  who  in-
cludes under the term " an&matosis " the affec-
tions which I have  grouped  under the head of
primary anaemia, with the exception of  chlo-
rosis.  The term is apt,  convenient and  com-
prehensive, but  has not been widely adopted.
While  admitting the  fundamental relationship
between these various forms of anaemia, I think
that better scientific work will be accomplished
by continuing to treat them as separate affec-
tions, by dwelling upon their points of diverg-
ence.  In fact, the  tendency of late  has  been
rather to separate than to unite  anaemia lym-
phatica and leucocythaemia.   Dr. Moxon  and
others  hold  that there  is no such  disease as
pure lymphatic leucocythaemia, the grounds for
which  will be  stated in  treating of leucocy-
thaemia. 
70
  The disease  may be defined as an infective
hyperplasia of the lymphatic tissue of the body,
with progressive anaemia.
  Symptoms.—These are due to the pressure of
enlarged glands and new formations of adenoid
tissue in  the  most various  situations, causing
stenosis of ducts,  blood vessels,  air passages,
oesophagus, etc. ; and to  the  profound disturb-
ance of nutrition and resulting anaemia, which
set in sooner or  later.  By the pressure of the
enlarged cervical and bronchial glands may be
caused cough, dyspnoea and difficult deglutition,
which  may all  be  aggravated by the simul-
taneous enlargement of the tonsils and retro-
nasal adenoid  tissue.  The cerebral  circula-
tion  may also be  disturbed by pressure upon
the cervical  veins.   In the  axilla,  enlarged
glands  may  cause brachial  neuralgia  and
oedema, and  enlarged inguinal glands  may
give rise to similar  disturbances in the lower
extremity.  Enlarged portal  glands may give
rise to ascites and jaundice.  Sensory and motor
paralysis  may be  caused by growths in  the
brain and spinal cord.  Digestive disturbances
may be due to the  growth of adenoid tissue in
various portions of the alimentary canal. As a 
71
rule, the glandular enlargement does not cause
pain and is not tender, or very slightly so, on
pressure.  The same is true with regard to the
spleen, but occasionally the hypertrophy of this
organ gives rise to a sense of weight and drag-
ging in the left hypochondrium, or even pain
that may radiate to the back and opposite side.
Pyrexia is frequent  during the course of the
disease, but  presents  nothing  characteristic,
being sometimes continuous, at others remit-
tent or irregularly intermittent.  Murchison and
De Renzi have each observed a case in which
the glandular enlargement, instead of gradually
increasing, was paroxysmal,  coinciding  with
attacks of pyrexia of several  days' duration.
After each attack the  enlargement subsided,
but remained  greater  than  before.   On  the
other hand, Laache has reported a case in which
during the febrile attacks the glands diminished
in size.  He  suggests,  in explanation, that  a
pyrogenic material may be absorbed from the
glands.  In the  great majority of  cases no
change  in  the  dimensions of  the  enlarged
glands is observed during the attacks of fever.
The remaining symptoms  are those of steadily
progressive  anaemia, namely,  muscular weak- 
72
ness, paleness of skin and visible mucous mem-
branes, palpitation of the heart with sometimes
a systolic murmur, frequent pulse, epistaxis,
oedema, and  serous effusion not accounted for
by mechanical obstruction.
  Diagnosis.—This presents certain difficulties
when the enlargement  remains for a long time
limited to one glandular  group.   It  is to be
distinguished from scrofula, sarcoma  and car-
cinoma.  Strumous glandular enlargement is
generally associated with other signs of scrofula,
such as affections of the bones, joints,  skin and
mucous membranes,  and  especially  with  the
characteristicyaaV^ of the  strumous diathesis.
The glands, too, are usually adherent to each
other and to the skin, and the morbid process
slowly advances to an  unhealthy suppuration.
In  sarcoma,  also,  the glands are adherent,
whereas the tumor of anaemia lymphatica is dis-
tinguished by the free mobility of the enlarged
glands upon  each other.  This communicates
an unmistakable sensation on palpation, which
Southey has aptly compared to that experienced
in handling  a number  of balls enclosed  in a
net.   Carcinoma is almost always  secondary,
and  extends  by glandular contiguity,  while, as 
73
already remarked, there appears to be no law
governing  the  direction  of  the  progress  of
lymphadenoma.   Leucocythaemia is  excluded
by a microscopic examination of the blood.
  Prognosis.—The prognosis of this disease is not
so hopeless as might be inferred from  the term,
" malignant lymphoma,"  applied to it by Bill-
roth.   In estimating the probable  course  of a
case, and its duration, the most important factor
is the stage which  the growth has reached.  If
local, a cure is not  only possible, but  highly
probable, provided the tumor is situated in one
of the superficial lymphatic groups ; that  is to
say, within the  province of surgery.  If the
affection has become general, the prognosis is
unfavorable ; but  even then, individual cases
present wide  differences  with  regard to  the
rapidity of their downward course, depending
chiefly upon the  amount of pyrexia and the
degree of anaemia.  The average duration of the
disease is about two years, but is  largely influ-
enced by  the preceding  health of  the patient,
being shortest in those of delicate constitution. It
has been observed to run a  very rapid  course
after parturition, especially when this had  been
accompanied with considerable hemorrhage. 
74
  Treatment.—An early diagnosis is the  most
important requisite to a successful treatment.
In most of the cases on record the affection has
remained limited  to one of  the  superficial
lymphatic groups  for a varying period, during
which  the propriety of extirpating the tumor
should be considered.  By this means the dis-
ease may sometimes be cured and its  progress
often  delayed.  The  enlarged  glands  must
sometimes be removed as a palliative measure,
when they threaten to destroy life by impeding
respiration or deglutition, or cause intense pain
by pressure upon nerves.  Friction over the en-
larged glands has been said to cause  a reduc-
tion of their size, and the same result has  been
attributed to the application of electricity.  The
general nutrition of the body should be main-
tained, as far as possible, by a diet as generous
as the digestive system can  dispose of.  The
anaemia  should be  combated with  iron  and
arsenic, and  the  latter is  believed to exert a
specific action when injected  into the morbid
growths.  Warfwinge  reports   several  cases
cured  by the intra-splenic  and intra-glandular
injection of Fowler's solution.  He injected four
drops of the solution thrice daily, and observed 
75
a steady reduction of the size of the tumors and
a gradual improvement of the condition of the
blood.
              LEUCOCYTHAEMIA.
  The consideration of this disease naturally
follows that of the one which has so often been
mistaken  for it.  From the point  of view that
the genuine  should always have precedence
over the spurious, it might well have come first
in order, but the object of this work, as its name
implies, is to keep prominently in view the anae-
mia common to the various disorders of which
it  treats.  From this standpoint, the anaemia
of pseudo-leukaemia, being uncomplicated, de-
serves the precedence.
  Nomenclature.—Of the two names of this dis-
ease, leucocythaemia (white-cell blood) and leu-
kaemia (white blood), the former is  certainly the
more accurate ; for the latter might be applied,
with equal propriety, to the appearance of the
blood after a meal containing an abundance of
fat, and in many cases the blood presents to the
unaided eye no deviation from the normal ap-
pearance.  Nevertheless, the term leucocythae-
mia  has been  practically rejected by German
writers,  whose  important contributions  to  our 
76
knowledge of this disease  entitle their prefer-
ences—or prejudices—to respectful considera-
tion.   I  shall, therefore, employ both  terms
interchangeably in the course of this article,
giving the preference,  when an  adjective  is
needed, to that derived from the shorter of the
two.
  Anatomical Characters.—This disease is pre-
eminently  one to which the  term organic or
structural may be applied;  for it cannot be said
to exist until a striking change in the  composi-
tion of the blood has become manifest.  The
degree of  this change — the increase in the
number  of the white  cells—necessary to con-
stitute the disease, is not agreed upon ;  and this
is not surprising, since, as all are aware, the
number  of these bodies in healthy blood can
only be approximately stated.  In health, after
meals, the number of leucocytes in the blood is
increased,  and this increase  coincides with a
congestion and tumefaction  of the  spleen, of
which the elastic capsule is specially adapted to
these periodic changes of volume.   This condi-
tion of physiological increase in the number of
the  white cells is known as  leucocytosis, and the
same term is applied to the undue proportion of 
77
these bodies sometimes observed in fevers and
during pregnancy.   A narrow boundary line
between leucocytosis and leucocythaemia cannot
be  drawn.  They are, rather, separated by a
broad strip of territory, which either may invade.
During the progress of a case of leucocythaemia
that may eventually end  in  death, there may
be periods of remission, during which the pro-
portion of white cells to red may be but little
removed from the normal;  and, on the other
hand, a state of the blood at first regarded as a
mere leucocytosis may gradually, by its  per-
sistence and further progress, convince  the ob-
server that he has to deal with a genuine leuco-
cythaemia.  The tendency, however, is, rather,
to regard leucocytosis as leucocythaemia than
the reverse.
  Three, forms of leucocythaemia are described
—the splenic, lymphatic and medullary, which
are secondary to changes in those organs—the
spleen, lymph glands  and bone marrow, uni-
versally  accepted as  hcematopoietic, or blood
making.   Cases have been supposed to be due
to lesions of other organs, such as the  thymus
and thyroid bodies, the tonsils and intestinal
glands, but these were mostly reported before 
78
Neumann had directed attention to the marrow
as a fons  et origo mali, and there is no proof
that such cases were not of the medullary or
myelogenous form.   As the affection is mostly
one of adult life—the greatest number of cases
occurring between thirty and fifty years of  age
—the part taken in its production by a foetal
organ, such as the thymus, is highly prob-
lematical.
  The first stage of the morbid process in  the
spleen is a hyperaemia, which may be so intense
in degree and  so rapid in development, as to
cause great enlargement of the organ and sen-
sations of discomfort, weight, and even pain, in
the left hypochondrium. The tissue of the gland
is soft and its surface irregular, the depressions
corresponding  to the insertions of the  fibrous
trabeculae. At this period the condition differs
only in its degree  and persistence  from that
which normally exists during digestion.  Soon,
however, the enlargement acquires a more per-
manent—a structural—foundation, from numer-
ical  hypertrophy of the  cells  of  the splenic
pulp.  The size  of the organ increases, and may
become so enormous as to fill the space between
the ribs and groin on the left side, and  extend 
79
beyond the umbilicus on the right.   The results
of inflammation of the capsule are commonly
apparent in the form of thickenings, opacities
and adhesions to neighboring  organs.   The
gross appearance of  the cut surface is variable.
Sometimes it differs  in no  respect from that of
a  normal spleen ; at others,  all traces of the
Malpighian bodies have disappeared ;  the sec-
tion is smooth and firm, closely resembling that
of the liver.  In the pure  splenic  form of leu-
cocythaemia the Malpighian bodies, while, per-
haps, plainly evident, are  not  enlarged.  They
become so  only in  the lymphatic and lieno-
lymphatic forms.  Hemorrhagic infarctions are
often observed.
   The  alterations  of the  lymphatic glands,
like those of  the spleen, are  due to simple
hyperplasia, and have been already described
in  the section  on  anaemia  lymphatica.   In
leucocythaemia  their  consistence  is  usually
soft.
   The changes in the bone marrow, to which
attention was first called by Neumann, are two-
fold.   In the first form it is of grayish-yellow or
yellowish-green color, and closely resembles a
thick, creamy pus ; in the second, more or less of 
80
red is mingled with the gray or yellow, until in the
most marked degrees of this variety the medulla
may be of the color of raw beef. These variations
in color are explained by Ponfick as being due to
varying densities  in the accumulations of white
cells  and  corresponding  variations  in  the
amount of blood in the vessels. The leucocytes
are seen, under the microscope, to be embedded
in an extremely  fine  reticular tissue.  In this
altered marrow there may be apoplectic extrav-
asations such as have been described as occurring
in the spleen and lymph glands.   The bones,
of which  the  medulla most frequently under-
goes these changes, are the sternum, ribs  and
vertebrae.
  In other than  lymphatic organs, any alter-
ations are  due to the altered state of the blood,
and consist of the fatty degenerations common
to anaemia in general  and of infiltrations and
nodular deposits  of leucocytes.  The infiltra-
tions are most common in the liver and  kid-
neys, causing considerable enlargement of these
organs. The nodules have been observed both
in the substance of  organs and  on their serous
surfaces, as well as on  the mucous membranes
of the air  passages and stomach.  The peri- 
81
toneum may be covered with gray, semi-trans-
parent nodules  varying in size from a pin's
head to a pea, and so closely resembling miliary
tubercle in their gross and microscopic appear-
ances that the absence of the bacillus may be
the only differential point.  The minute struc-
ture of the nodules of this " leukaemic peritonitis"
may also resemble that of alveolar sarcoma, as
in a case described by  Laache.
   Changes  in   the  Retina.—In well-marked
cases of leucocythaemia,  certain  retinal lesions
are commonly observed,  to which attention was
first directed by  R.  Liebreich in 1861.  Being
generally   situated near  the  periphery of the
fundus oculi, they but seldom cause any visual
disturbance, and, therefore, their  frequency can
only be estimated by an ophthalmoscopic ex-
amination  of all  cases.  The  eye-ground is of
an orange-yellow hue,  its veins pale and wider
than normal, and traces of  hemorrhage are
scattered along  their course.  Other  spots are
observed,  of  which  the  appearance  indicates
a more compound structure than that of mere
hemorrhage.  They have a whitish-yellow cen-
tre and a reddish border  of extravasated blood,
and are  analogous  to the lymphoid deposits
      F 
K2
in other tissues.   The  cause of these  retinal
hemorrhages is twofold.  They are favored by
the malnutrition of the vessels from deficiency
of red corpuscles, and excited by the obstructions
from excess of the white.
  Changes  in the Blood.—The  characteristic
feature of leucocythaemia  is an absolute  in-
crease in the number of white blood cells, which
in extreme degrees of  the disease may be
even greater than that of the red.  This alter-
ation in  the cellular composition of the blood
may alter  its  macroscopic  appearance  by
causing  it  to assume a  pale-red, grayish-red,
or chocolate  color ("milchchocolade") ; but  it
would be exceedingly rash  to predict the exist-
ence of leucocythaemia  from a gross examina-
tion of a specimen of blood. Such a caution
will not  seem unnecessary to those who, like
myself, have seen  a case reported as leucocy-
thaemia in which the blood was never examined
at all.  The white cells are by no means uni-
form in  size.  In one  of Mosler's cases  the
smallest  were one-third  smaller  than  the red ;
the largest  four times larger than the  red.   It
is doubtful whether, as Virchow  supposed,  any
diagnostic significance can be attached to such 
83
variations ; for in a case of pure splenic leucocy-
thaemia the leucocytes  have varied  in diameter
from  5 fi  to  15//.  Virchow holds  that in the
latter variety the leucocytes in the blood are
identical with the cells of the splenic pulp, and
that in the lymphatic form they are uninucleated
like the cells of the lymphatic glands. Before
attempting, however, to make the diagnosis of a
disease, it is necessary to establish its existence,
and that of  the so-called  lymphatic leucocy-
thaemia is emphatically called in question.  In
the medullary form, Neumann has found in the
blood, red nucleated cells such as normally in-
habit the marrow, and regards them as charac-
teristic of this  variety.  They  are  not always
present, having been  searched for in vain by
Mosler in a typical case of  medullary  leu-
kaemia {Berl. klin.  Woch., 1876, No. 49).
  The degree  of  anaemia  is rarely  extreme.
 ases may steadily proceed to a fatal termina-
tion without a reduction of more than fifty per
cent, of the normal number of red corpuscles,
although  exceptional cases  occur  in which the
number of red corpuscles is exceedingly small;
for example  ,0.5 million per cubic millimetre.
There are no characteristic changes in the size 
S4
and shape of the red corpuscles.  The value of
the latter (their percentage of  haemoglobin) is
well maintained, rarely  sinking below seventy-
five  per  cent.   A  point  of some  importance
with reference to the pathogeny of  the disease
is  that the number of white and red cells  to-
gether is less than that of the normal number of
red.  Certain pointed octahedral crystals were
discovered in leucocythaemic blood  by Charcot
in 1853,  identical with those subsequently ob-
served by Leyden, in  1871, in  the  sputa of
asthmatics.  In i860, in a case  reported by Dr.
Calvin Ellis, Dr. White found  " numerous mi-
nute crystals.   They were colorless, elongated,
faintly marked, rhombic  octahedra, exhibiting
irregularities of form, indicating an  organic na-
ture."  To these crystals  he gave the name of
" Leukosin."  In 1863 Dr. Howard  Damon dis-
covered, in the leucocythaemic  blood  of a boy,
certain crystals which, he asserts, " differed en-
tirely, in form, size, color, degree of  resistance
at atmospheric influences, refractive  and other
properties, from all known crystals of the human
blood.''  They were composed of " hexagonal
and pentagonal plates of  unequal sides, of rec-
tangular  plates in the form  of squares and 
85
parallelograms, and also  of a  few triangular
plates.  Some of these crystals  were  twice the
size  of the  red  blood corpuscles  in  the  same
field of view." The name of "Leucocrystallin "
was  applied to them by Dr. Damon.*  Certain
normal  constituents of the spleen have been
found in leucocythaemic blood, such as lactic
and  formic acids, leucine and hypoxanthine.
The  specific gravity of the blood is diminished
in leucocythaemia owing to the fact that the red
corpuscles  are replaced by the lighter  leuco-
cytes ; and, further, because the normal propor-
tion  of water is  retained.  The proportion  of
fibrin is, as a rule, increased.
  Clinical  History.—In the insidious  nature  of
its onset,  and its gradual  progress,  leucocy-
thaemia resembles many fatal diseases which run
a chronic  course.  The first  symptoms  com-
plained of are those of anaemia in general, such
as muscular  weakness, lassitude,  indisposition
to exertion, either physical or mental, anorexia,
indigestion, and dyspnoea, on exertion.  As the
case  progresses, other symptoms arise, of which
some are to be attributed to leukaemic deposit  in
* See Bolyston Prize Essay on Leucocythaemia, 1864. 
Sli
the parts  affected.  Among these are hemor-
rhages,  either spontaneous  or traumatic;  the
former variety being most commonly met with
in the form of epistaxis ; the latter, after the ex-
traction of teeth.   Diarrhoea  is now the rule,
and oedema of feet and legs and ascites finally
set in.  The last-named  symptoms are most
common when the spleen is greatly enlarged
and indurated, and are favored by  deposits in
the liver and by the leukaemic  peritonitis above
mentioned.  Singular anomalies are sometimes
observed in the course of this disease.  For ex-
ample, although the appetite is generally mark-
edly  deficient, often to the point of absolute
anorexia,  it  may be  voracious, as  in a case
observed by Prof. Da Costa (Am. Jour. Med.
Sci., Jan. 1875), in which, in spite of an inordi-
nate  consumption of food and  the  absence of
diarrhoea,  the loss of flesh was  progressive.  On
the other hand, in a case reported by Mosler, in
which the  blood  was chocolate-colored and the
white  cells were  to the red as  two to three, the
digestion was unimpaired and  the body weight
maintained.   Dizziness, aggravated  by move-
ment, may  be a marked symptom.  In  the
splenic  form,  sensations of weight, dragging 
87
and pain are felt in the left hypochondrium ; and
in the  medullary variety, tenderness of bones,
particularly  the  sternum, may be  detected.
Visual disturbances may be due to hemorrhage,
to leukaemic deposit, or to leukaemic retinitis ;
but marked retinal changes may be  observed
in cases which have presented no symptoms of
eye disease.  There is no peculiar facies of this
disease.  The extreme pallor of pernicious anae-
mia  is rarely  observed.  On  the contrary, the
cheeks often  present  a  circumscribed flush,
even in a late stage of the affection.  There is
nothing typical  in  either pulse or  respiration,
but fever of irregular type is invariably met with
at some period of the  clinical  history.  The
proportion of white cells to red is diminished by
the occurrence of suppuration  in any part of the
body.   When  the leukaemic cachexia is fairly
established, the enlarged spleen  may diminish
greatly in size without any corresponding im-
provement in the symptoms.  In a case reported
by Laache, the spleen, which  had projected to
the right, beyond the median line and downward
almost to the symphysis  pubis, gradually con-
tracted until, just before death, it extended but
three centimetres below the left costal border. 
88
  Hypoxanthine is found in the urine as well as
in the blood, and in the former fluid the pro-
portion of uric acid is increased, sometimes to
six or eight times the normal.
  A division of the course of the disease into
two stages has been suggested: the first  con-
sisting of the development of the morbid pro-
cess in the haematopoietic organ or organs first
attacked and in  the blood;  the  second, of the
extension  of the process  to other non-lymphatic
organs. This division, although excellent from an
anatomical standpoint, is too objective for clinical
purposes.  The secondary leukaemic deposits can-
not be detected, as a rule, in  any organs but the
lymph glands, assuming, for the moment, that
the enlargement of these organs is secondary.
  Pathogenesis.—To  properly appreciate  the
cause of any deviation from the normal com-
position of the blood, it  is necessary to  under-
stand how that  composition is produced and
maintained.  In the problem  before  us—the
nature of leucocythaemia—the first step is to de-
cide whether there is any normal relationship
between the red and white  cells.   If-there be
any, it is  manifest that  the red, on  account of
their greater functional  importance, their size, 
89
shape, color and number, are derived from the
white, and not the white from the red.  The
question, therefore, is one concerning the origin
of the  red corpuscles;  and  those who have
studied it will doubtless agree  with  me that
there is scarcely a subject in physiology con-
cerning which our notions are so  fragmentary
and  confused.  This being the  case, it  is im-
possible to offer more than an hypothesis of the
nature of leucocythaemia.
  All authorities  are agreed that  in adult life
the lymphatic system—in which are  included
the spleen, lymphatic glands, and red marrow
—is the sole source of the red blood corpuscles.
The  cells of the splenic pulp, the  smaller uni-
nuclear cells of the lymphatic ganglia, and the
red,   nucleated  marrow-cells—first  described
by Prof.  Neumann, of  Kbnigsberg,  in 1868,
and subsequently called by Malassez,  "cellules
hemoglobiques''—are by some, perhaps different,
means converted into the  bi-concave  discs of
the circulating blood.  Time is requisite for this
conversion—a time of incubation in the blood-
making organs.   Any  unusual activity of the
circulation in these glands  may hasten the exit
of their cells, and cause them to appear in the 
90
blood in an immature condition. This is demon-
strated  by the physiological  concurrence of
leucocytosis with splenic post-prandial conges-
tion.  In leucocythaemia,  there is a persistent
hyperaemia of spleen  or  other  blood-making
organ, which prevents the leucocytes from at-
taining their proper development.   They enter
the circulation as  leucocytes.  This  view is
endorsed by  Dr.  Richard Norris, of  Birming-
ham,  and  held by others, who do not  agree
with him concerning the stages of the process
by which the white cells are normally elaborated
into red  corpuscles.  Norris contends that in
health the great majority of the leucocytes in the
blood-making organs are, before entering the
circulation, converted into a pale, colorless, bi-
concave  disc, which he terms the  " advanced
lymph disc."   This corpuscle  acquires haemo-
globin, and with it its full functional perfection.
The white blood  corpuscles  represent  those
leucocytes which have prematurely  entered the
circulation, for instance after a meal. These lat-
ter, however, may develop into red corpuscles
in the  circulation.  The  former mode of ori-
gin of red corpuscles  Norris calls the " major
process"  of  blood-formation ; the latter, the 
91
" minor process," and, therefore, in accordance
with his views, " leukaemia, in a word, is  the
encroachment of the minor  upon  the  major
process of blood-making."
  Several observers have noticed a diminution
or absence of amoeboid movement in the white
cells of leucocythaemic  blood.  " The earliest
observations on this point were made by Dr.
Laking,  in  1873, but  remained unpublished.
The results were communicated  by Dr. Pye-
Smyth to the Pathological Society in 1878, and,
in the same year, to the Lancet, by Dr. Cafavy.
Neumann also, in 1878,  found amoeboid move-
ments wanting, or very sluggish,  in a case  of
leukaemia,  although they were active in the
corpuscles  of fluid from blisters  in the same
patient."   (Lancet,  1880, ii,  769.)  Dr.  John
Cafavy, who has given special attention to this
subject, concludes that " the colorless corpuscles
in leukaemia are dead,  or dying,  and hence
incapable of development."   This functional
incapacity of the white cells may be referred to
the shortness of their stay in the lymphatic
organs, of which  the hyperaemia prevents their
reaching the normal term of  their gestation.
They are to be regarded as abortive products. 
02
  Under this section  it is appropriate  to con-
sider the question, which has been raised, as to
whether the customary division of this disease
into three varieties, the splenic, lymphatic and
medullary, is warranted.  A primary splenic
leucocythaemia  being  universally accepted, it
remains to  consider  whether  the  lymphatic
glands and the bone marrow may be the start-
ing point of the  disease.  Some authorities,
while not explicitly rejecting the lymphatic and
medullary varieties, do so tacitly by describing
no other than the splenic.   Dr. Moxon is  the
most  outspoken upholder of the  doctrine that
the spleen is the only starting point of leuco-
cythaemia, and  emphatically rejects the theory
of a lymphatic  leukaemia,  which he stigma-
tizes as a "myth."  He holds that  the enor-
mous accumulations of leucocytes in the lymph
glands  and bone  marrow  are secondary  de-
posits  from the blood, and, in support of this
view,  he has demonstrated that the  leucocytes
normally present in the lymph spaces—which
have been shown by Dr. Klein to be out-wan-
dered white blood  cells—are greatly increased
in number in cases of leucocythaemia.  These
cells  are  conducted  through the  lymphatic 
93
vessels to the glands, and if these are pervious,
re-enter the blood; if not, the  glands  enlarge
by  the  continual  accession  of out-wandered
blood cells ; " so that," Dr. Moxon concludes,
" lymphatic leukaemia is  a myth ;  and  the
pathology of leukaemia, now so complex, should
be simplified, when it will better  conform with
the clinical uniformity which characterizes the
disease."  I am inclined to accept Dr. Moxon's
opinion in so  far as the lymphatic variety is
concerned, for the reason that in  anaemia lym-
phatica we find a lesion of the glands identical
with that which exists in lymphatic leukaemia.
The last-named affection, assuming its existence
for  the sake of the  argument,  is  made  up of
lymphatic anaemia plus leucocythaemia.  I  be-
lieve, however, that  there is  substantial  proof
of the existence of a primary medullary leukae-
mia.  For example, in a case observed by Vir-
chow, fracture of the femur appeared to be the
determining cause.  In another,  reported by
Mursick, the disease attacked a soldier five
days after amputation for a gunshot wound of
the knee-joint, and at the autopsy osteo-myelitis
of the femur was found.  The patient had been
previously healthy.  In the remarkable case of a 
94
sea captain, reported by Mosler, in whom the dis-
ease followed prolonged exposure to cold during
an Arctic winter, pain and tenderness over the
entire length of the sternum were among the
earliest symptoms, and speedily became so in-
tense as to compel the man to desist from any
kind of manual work.  The  list of cases such
as those last referred to  is so long, and the
cases  themselves  so  remarkable, that those
who are at all familiar with them feel the ne-
cessity of great caution in  discussing the ques-
tion of  a primary medullary leukaemia.   As
above stated, I believe the evidence is in favor
of such an  affection, and, with the  object  of
obtaining further confirmation, I would suggest
to hospital surgeons and their assistants the im-
portance of  examining the blood after injuries
of the bones.
  ^Etiology.—The male sex is more predisposed
to this disease than the female, the male cases
on record standing to the female in  the  pro-
portion of about two  to one.  The influence of
age is not striking, although the disease occurs
most frequently during adult  life,  and between
the ages of thirty and fifty.  Neither  infancy
nor old age is exempt.   Cases in infants  of 
95
fifteen and sixteen months have been  reported
by Trousseau and Mosler, and one of Vidal's
cases was sixty-nine years old.  Dr. Goodhart
has also reported to the Clinical Society of Lon-
don six cases under two years of age.   Poverty
includes, in one word, a number of predisposing
factors, such  as  an  unfavorable  hygienic  en-
vironment, insufficient food, and the depressing
emotions  of  care and  anxiety.  A few cases
have been attributed to traumatism of the spleen,
and  others, as already stated, to that of the
bones.  There can, I think, be  no doubt that
long-continued  exposure  to  severe  cold  has
excited the disease in several instances.
  Diagnosis.—This can be made in no other
way than by a microscopic examination of the
blood, and to warrant the diagnosis of leucocy-
thaemia, the increase in the number of the white
cells must be  absolute as well as relative.   In
well-marked cases  the  microscopic inspection
of a drop of blood will suffice for the barest pur-
poses of diagnosis,  but will give no idea of the
grade of the affection.  With the latter object
in view,  the  number of red and  white cor-
puscles in a given volume of blood—a cubic
millimetre—must be estimated by means of a 
!)6
hemacytometer, such  as that  of Gowers or
Zeiss.  I have more than once  refuted a  di-
agnosis of leucocythaemia  which had  been
made by the examination of a drop of blood
under the microscope.  In one of the cases the
diagnosis  thus made  seemed  unmistakable,
but on carefully counting the red and white
cells, I found a great reduction  of the former,
and a proportion of one to eighty between the
white and red, but the number of the white cells
Per cubic millimetre was within normal limits. In
every case of profound anaemia in which the
number of  white cells is not reduced pari passu
with the red, the diagnosis (?) of leucocythaemia
is liable to  be made, unless  the most accurate
methods of investigation are employed.   I have
seen as many as from twelve to fifteen white
cells in each microscopic field of a specimen of
blood  of  which a more careful examination
showed that the increase was merely relative.
The liability to error being so great, what is the
increase, absolute and relative, which warrants
the diagnosis of leucocythaemia ?  There is no
fixed rule.  Each observer is a law unto him-
self.  For my own  part, if the number of leuco-
cytes per cubic millimetre is increased (i. e., if 
97
they are more than 10,000), and if the propor-
tion of white cells to red is as great as one to
fifty, I consider that the limits of leucocytosis
have been overstepped.  This is confirmed by
the co-existence of great tenderness of sternum,
ribs or vertebrae, and made  absolutely certain
by the detection of any enlargement of the
spleen.  As to the question whether the pre-
cise variety of the disease may be  ascertained
by an examination of the blood, there is little
to be said.  As already mentioned under the
head of changes in the blood, the size of the
white  cells may vary  greatly in  the  purely
splenic form.   The presence of red nucleated
cells in the blood is believed by Neumann to be
pathognomonic  of the  medullary variety, but
their absence  does not  exclude an  implication
of the marrow.  The  absent  or  diminished
amoeboid movement of the white cells is a point
with which diagnosis is not so much concerned
as pathogenesis, and, therefore, it has been re-
ferred to under the latter head.
  Dr.  Richard Geigel {loc. cit.) has suggested
and practiced  the following method  for making
easier the counting of the white cells.  To fifty
cubic centimetres of a one-half of one per cent.
      G 
98
chloride  of sodium  solution,  are  added four
drops of a one  and one-half per cent, solution
of gentian violet, and by using  this  in  the
counting of the corpuscles, instead of the ordi-
nary diluting fluid, the red corpuscles are  un-
altered, while the leucocytes are stained blue,
so that it is impossible to overlook a single  one
of them.
  The diagnosis of leucocythaemia having been
made with the  microscope, its variety is to be
determined by the ordinary methods  of physi-
cal  diagnosis.  A case  in  which  the  spleen
is increased in size, while nothing abnormal
can be detected in lymph glands or  bones, is
one of pure  splenic leukaemia.  Combinations
of enlarged spleen and lymph glands are desig-
nated as lieno-lymphatic or lymphatico-splenic,
in accordance with the supposed priority of the
organ affected.  The medullary form  may also
be complicated with an enlarged spleen  or with
hypertrophied lymphatic ganglia, and  the same
remarks are applicable to it.
  Prognosis.—In  the earliest stage, that of hy-
peraemia of the haematopoietic organ involved,
a cure may be  effected by a proper course of
treatment.  The prognosis is more unfavorable 
99
when the enlargement of spleen or other organ
is maintained  by  numerical  hypertrophy of
its cells, and becomes absolutely so when the
leukaemic infection  has become general.  The
latter event—the establishment of the leukaemic
cachexia—may sometimes be demonstrated by
an inspection of the fundus oculi, in which leu-
kaemic  deposits are readily seen.  A  not un-
common mode of death is apoplexy, to which
there is a predisposing cause from malnutrition
of vessel walls, and an exciting one from ac-
cumulation of leucocytes within their lumina.
  From one to three years is the average dura-
tion of the disease.
  Treatment.—The cures reported have been
mostly in children, which may be owing to the
fact that their impressible systems render easier
an early diagnosis.   The very fact that  their
powers of resistance are less than those of adults
is thus favorable,  from a therapeutic stand-
point.   Dr. Goodhart has reported to the Clini-
cal Society of London six cases of children,
under two years  of age, which were -cured by
the administration of either phosphorus, iodide
of iron, or cod-liver  oil.  In  all of them the
spleen was moderately enlarged and the white 
100
cells increased about tenfold.  Mosler also has
reported the cure of a boy of ten  years, who
" took a drachm and a half of sulphate of quinine
in the course of four days, and then ten grains,
and afterward six grains daily ;  he completely
recovered."  The case was of the splenic form.
Mosler prefers quinine to all internal remedies,
but recommends  also the employment of oil of
eucalyptus and piperin, in accordance with the
results of certain experiments by himself and
Hans Scenderop, which  show that both these
substances cause contraction of the spleen  in
dogs.  They may be prescribed in pill, as in the
following formula:—
  R-.  01. eucalypti,              gtt. ioo
      Piperini,
      Cerae albse,        aa      3)
      Pulv. althese,              3 ij.
     M. et ft. pil. No. C.
  SiG.—Three to five pills thrice daily.
  Careful counts of the blood corpuscles during
the employment of arsenic, have proved  that
this drug has a  favorable  influence over the
course of leucocythaemia. It should be given in
full doses and pushed to the point of toleration.
A local  treatment of the enlarged spleen by 
101
means of electricity, cold douches, and ice bags,
has been practiced, and often with the result of
materially  reducing  its size.  Once, however,
the disease is fairly established, the spleen may
fluctuate very greatly in size, without any cor-
responding effect upon  the patient's condition.
In  the  early stage of the splenic form, local
treatment should not be neglected.  Botkin re-
ports a case of lieno-lymphatic  leukaemia  in
which faradization wa's followed by a consider-
able  reduction  in the long and transverse
diameters of the enlarged spleen, which coin-
cided with improvement in the  general con-
dition of the patient.  In opposition it must be
stated that  Mosler has not been able to confirm
th« statement that the  size  of the spleen is re-
duced by faradization,  but  has seen its long
diameter apparently diminished by being pushed
upward  by the  contraction  of the abdominal
muscles.   Transfusion  of   defibrinated  blood
has been  employed  with  marked temporary
benefit, but cannot be  regarded  as a curative
measure.
   Extirpation of the  spleen  is only mentioned
for the purpose of condemning it.
   Postscript.—Although not without an opinion 
102
 concerning the rival claims of Bennett and Vir-
 chow to the discovery of leucocythaemia, I have,
 thus far, purposely refrained from expressing it.
 It appears to me that the credit of having pre-
 sented the subject of leucocythaemia in such a
 light as to attract the notice of the whole pro-
 fession, and to convince Bennett that six weeks
 before he had discovered a  new  disease, un-
 doubtedly belongs to Virchow. I also think that
 when a labored argument, such as that of Ben-
 nett, is  necessary to make good a claim, it is
 self-evident that the right of  possession can be
 called in question.

             ANAEMIA  SPLENICA.
   Definition.—This disease, which is the splenic
form of'pseudoleukcemia,  is completely ignored
 by nearly all the numerous  text books,  hand
 books, systems and cyclopaedias of medicine.
 Even Dr. Adolph Striimpell,  who published an
 elaborate article in the Archiv der Heilkunde,
 Vol. XVIII, 1877,  entitled  Zur  Kentniss der
 Ancemia  Splenica,  devotes  but eight  lines to
 this subject in his recent text book of medicine.
 Although apparently unknown to most of the
 writers of the works above  mentioned, splenic 
103
anaemia has long been recognized as a distinct
affection by those who have paid special atten-
tion to  diseases of the haematopoietic organs.
For example, in  the course of an article on the
" Relations of Leucocythaemia and Pseudoleukae-
mia," in  the American Journal of the Medical
Sciences for October, 1871,  Prof. Horatio C.
Wood remarks:  "1 now desire to  show  that
there is still a third form of pseudoleukaemia—a
splenic variety.   Under the names of tumor of
the spleen, splenic cachexia, etc., from time far
back, medical records furnish accounts of cases
which I believe represent this affection."  He
then proceeds to report a typical case of anae-
mia splenica.
  The best account of this affection that I have
been able to find in medical literature is by Dr.
Guido  Banti {Annali  Universali di Medicina
Chirurgia-Parte  Rivisla,  1883), and is based
upon a critical study of three cases :  a woman
of 73, a boy of 18, and a girl of 16.   To it, as
well as to the  article  by Stnimpell  above re-
ferred to, I am largely indebted for the follow-
ing description.
  Anatomical Characters.—The cadaver pre-
sents the well-known appearances of extreme 
104
 anaemia, and there is usually a certain amount
 of subcutaneous  oedema  and serous effusion.
 The spleen, while retaining  its shape, is en-
 larged, sometimes to thrice its normal size ;  its
 tissue  is more or less indurated, and its in-
 cisures deeper than normal.  The capsule pre-
 sents patches of thickening and opacity, and  is
 sometimes adherent to neighboring organs. On
 the surface of a section which is of a reddish-
 brown color, white or yellow-white spots, usually
 not exceeding the size of a pea, may often be
 observed.  With the  microscope,  it is found
 that the normal adenoid tissue has more or less
 completely disappeared, its place being more
 than supplied by a thickening of the reticulum,
 which, in parts of the organ, may be so great as
 to form parallel bundles of fibrous tissue, con-
 taining narrow lacume, in  which are embedded
 a few lymphatic cells.  The change is precisely
 similar to that of the indurated glands in anae-
 mia lymphatica, and in order to emphasize the
 fibrous character of the alteration in both these
 diseases,  Banti proposes  for it the  name  of
fibroadenia.   In the heart  and voluntary mus-
 cles, fatty changes are the rule.  The blood
 corpuscles  are notably   diminished.   From 
105
5,000,000 per cubic millimetre, they gradually
descend to four, three, or even one million.  In
a case of my own their  number  was between
one and two millions.  They  present the same
alterations in size and shape as are encountered
in all pernicious forms of anaemia.   Notwith-
standing  Banti's assertion that red  nucleated
cells have never been observed in the blood of
splenic  anaemia, they  are said, by Strumpell,
to have  been numerous, in  his case, in blood
from the veins of the lungs, liver and spleen.
They varied greatly in  size  and  shape, and
were  mostly uninuclear, although some con-
tained two nuclei,  and a  few contained three.
With reference to the proportion of white cells,
the cases may be divided into two classes.  In
the first, the normal number of white cells is
not surpassed.  In  the second, the white cells
are increased in number, without, however, ex-
ceeding the  limits  of leucocytosis. Their pro-
toplasm  is granular, and, on the addition of
acetic acid,  becomes transparent, and  shows,
as a rule, but one nucleus. They do not contain
pigment  granules,  and, on a warm  stage,  ex-
hibit well-marked amoeboid movements.
  The marrow  may present  the  changes that 
106
have been erroneously supposed to be peculiar
to the so-called progressive pernicious anaemia.
In Striimpell's case the medulla of sternum, ribs,
and tibiae, was of a dark-red color, and of un-
usually firm consistence, and presented the fol-
lowing minute changes:  i.  Scarcely  any  fat
cells were  present.   2. The colorless marrow
cells were of  widely  different size and  shape,
mostly uninuclear, though some contained two
nuclei and others enclosed red blood corpuscles.
3. Besides the ordinary red blood  corpuscles,
there  were  numerous round,  pale-red, non-
nucleated cells of different size, and many  red
nucleated cells of varying size and shape, some
round, others elliptic; the  former  sometimes
granular, the latter mostly homogeneous.  Their
nuclei were often  double, and of the same pale-
red color as the rest of the cell; sometimes of
a more  yellowish tinge.  Occasionally,  the
nucleus was enlarged so  as to almost fill  the
entire cell; often  it was placed eccentrically.
  Clinical History.—The  disease may be pro-
perly  divided  into three  stages, of which  the
first, the enlargement of the spleen, is often
so insidious as to  pass for a long time  unob-
served by both patient and physician.  It mani- 
107
fests itself more frequently by a sense of weight
in the left  hypochondrium, which may be ex-
perienced only when in the upright position.
Sometimes,  however, it gives rise  to  severe
neuralgic paroxysms.  The second stage, that
of anaemia, presents the phenomena of anaemia
in general,  such  as pallor of skin and mu-
cous membranes, dyspnoea,  cardiac palpitation
and fatigue, on slight exertion.  These symp-
toms increase in severity until the third stage,
that of cachexia, is reached. The distinguish-
ing features of this stage are hemorrhage and
fever.  The skin is now the color of yellow wax;
the muscular prostration is extreme ; the men-
tal state is one of hebetude, and the oedema and
serous effusions increase.   The adipose tissue
generally disappears to a greater or less extent,
but  is  sometimes  preserved.   The  disease,
instead of being continuously progressive, may
recur in separate attacks, between each of which
there may be intervals of good health, of several
months' duration.  This intermittent character
of the affection was particularly well marked in
the case reported by  Strumpell, that of a young
man, aet. 25, who,  in  the  course of eighteen
months, was the subject of four attacks of pro- 
108
found anaemia, each of which  coincided with
enlargement of the spleen. Twice he recovered
from an apparently hopeless condition.  A third
attack  ensued  after several  months of good
health, and  he was again improving when he
fell into a state of melancholia,  during which
the fourth attack occurred and was fatal.
  Careful examinations of the urine were made
by Striimpell in the case referred to.   It was
always acid, never  contained  albumin and,
notwithstanding the icteric  hue  of the skin,
never responded to the tests for  bile pigment.
Repeated examinations showed that the greatest
destruction of albumin in  the  body, inferred
from the amount of nitrogen excreted, coincided
with the worst periods of the anaemic attacks.
This fact  is in perfect  analogy with certain
physiological experiments of Bauer and Frankel.
The former found, after bleeding  animals, that
the destruction of albumin in their bodies was
augmented.   The  same was  true in cases of
phosphorus  poisoning,  in which  there  is  de-
struction of  red cells.   Frankel  demonstrated
an increased excretion of urea after any obstacle
to respiration had been placed in  the large air
passages.  A similar increase had been demon- 
109
strated  in  cases of carbonic  oxide  poisoning.
As is well known, in cases of CO poisoning the
functional power of the red corpuscles is para-
lyzed ; they cannot carry O until the CO is dis-
placed.  In a word, experiments show that any
cause which interferes with the conduction of
oxygen to the tissues may produce secondarily
an increased destruction of albumin in the body ;
and  this is found also in states of profound
anaemia in which  the diminished consumption
of O is inferred with almost absolute certainty
from the fact of  an enormous destruction of O
carriers, and is  confirmed by the presence of
fatty degeneration of heart, blood vessels, etc.
   Nature of the  Disease.—Although anaemia
splenica has been generally  confounded with
other forms of pernicious anaemia, there can be
no question that it constitutes a  distinct patho-
logical entity. The enlargement of  the spleen
is  primary,  the  anaemia  secondary;  as  to the
relation between them, there are  two hypotheses
—to wit: Either the altered spleen directly de-
stroys the red corpuscles,  or in  it  are  formed
materials which  enter the circulation and inter-
fere with  the functions of haematopoiesis.  Of
these  views, Banti espouses  the latter.   With 
no
regard to the primary enlargement of the spleen,
nothing is known. That the disease is the splenic
form  of pseudoleukaemia, is, according to the
author just cited, proved by the following facts.
In pseudoleukaemia (i.e.,  anaemia lymphatica,
or Hodgkin's disease), the lymphatic glands are
rarely  the  only organs  affected; generally the
spleen is enlarged at the same time.   In some
cases, the enlargement of the spleen is in much
greater proportion than that of the glands, and,
finally, there are cases (and these belong to the
category of anaemia splenica) in which the spleen
is alone involved.
  The view that this disease is the splenic  form
of pseudoleukaemia  may  be opposed on  the
ground that the morbid changes in the spleen in
anaemia splenica are not identical with those of
the same organ when affected in anaemia lym-
phatica.  In the latter disease, the malpighian
bodies of the spleen, when that organ is second-
arily affected, are hypertrophied to  such an
extent that, as I  have said under the head of
"Anaemia Lymphatica," "their white or yellow-
ish color, like that of the lymphatic glands, con-
trasted with the dark-red color of the pulp, gives
to the cut  surface  a  characteristic  variegated 
Ill
appearance."  This change is beautifully shown
in a plate illustrating an article on Lymphade-
noma by Dr. Murchison,  in  the London Path.
Soc. Trans., vol. XXI.  In marked contrast to
this description, the spleen, in the case reported
by  Prof. H. C. Wood, was much enlarged and
indurated, but the " malpighian corpuscles were
not at all evident."  In summing up  the ana-
tomical characters of the  disease, Banti says,
with reference to  this point:  "The histological
alterations of the  spleen consist of an atrophy
and sclerosis of the malpighian corpuscles," etc.
  These apparent discrepancies  may be  ex-
plained in this manner:  The spleen is not a
lymphatic gland,  but contains within its pulp
numerous bodies—the malpighian corpuscles—
analogous to the lymph glands.  As  the latter
may,  or may not, be enlarged in cases of pseu-
doleukaemia—using  this term  in its  broadest
sense—so their analogues in the spleen may, or
may not, be enlarged.
  Course  and  Prognosis.—The  duration of
splenic anaemia is from five  or six months to
three  years.  These figures are certainly within
the  mark,  for  in  all the  cases, owing  to the
insidious nature of the onset, more or less of 
112
the first stage passes unobserved.   The disease
sometimes occurs in separate  attacks, from  all
of which, except the last, there may be complete
restoration  to  health; and, on account  of this
peculiarity in its course, there is great danger of
prematurely reporting cases as cured.  According
to Strumpell,  permanent  cures are  unknown ;
but this opinion must be modified in  favor of a
few cases in which splenectomy has been prac-
ticed successfully.
  Diagnosis.—The  tumor being recognized  as
an enlarged spleen, by its situation,  shape and
mobility during respiration, the question  arises
as to the character of the  enlargement.  There
is no difficulty in  distinguishing  the tumor in
anaemia splenica from other tumors of the spleen
which alter its  normal shape, such as carcinoma
and echinococci, but the tumors of amyloid
disease, paludal cachexia and leukaemia are to
be carefully differentiated.  Amyloid disease is
secondary to suppuration, especially in or about
the bones;  to syphilis, or to phthisis, and is not
confined to the spleen.  It may be demonstrated
at the same time in  the liver,  and perhaps also
in the kidney, by an examination of the  urine.
Leukaemia  splenica is  excluded by a  careful 
113
count of the white and  red  cells;  and paludal
cachexia by  the history  of the case and the
presence in the blood of the plasmodium ma-
lariae.
  A case  of anaemia of high grade associated
with a uniform splenic enlargement, not mala-
rial, leukaemic, or amyloid, can be no other than
one of anaemia splenica.
  Treatment.—The medical means of relief are the
same as those employed in other pernicious forms
of anaemia,  and  have been, thus far, attended
with but little success.  Among them are the
salts of quinia, piperin, oil  of  eucalyptus, and
arsenic. The latter may be given by the mouth,
or may be injected into  the splenic pulp, as has
been done with marked success by Warfwinge,
in cases of anaemia lymphatica.
  Faradization should be given a thorough trial;
for, even admitting that it has  no direct effect
upon the spleen,  there is reason to believe that
a salutary  influence  is  exercised upon that
organ  by the  contraction  of  the  abdominal
muscles.
  Pain, vomiting, diarrhoea, ascites and epistaxis
are to be treated  in the same manner as in other
diseases attended with these symptoms.  Banti
       H 
114
has tabulated the cases of splenectomy  per-
formed for non-traumatic lesions. They number
twenty-one,  of which  four were  undoubted
cases of anaemia splenica.   Of these four, three
recovered.
           PERNICIOUS ANEMIA.
  Nomenclature.—The term idiopathic was first
applied by Addison to certain cases of profound
anaemia of unknown origin, which were in all
respects  identical  with  those  subsequently
described by Biermer, in 1872, under the title
of " progressive pernicious anaemia."  In the
latter term the adjective " progressive " appears
to me  not  only unnecessary but, to a certain
extent, absurd ; for all diseases are progressive
in one or other direction.   In  using the  term
" idiopathic," Addison was, no doubt, impressed
with the idea that when the anatomical basis of
a disease is unknown, it is best to apply to it a
title acknowledging that ignorance.   This I re-
gard as an error.  It is  one thing to acknowl-
edge ignorance and  another to parade it.  A
terminology based upon etiology is doubtless the
most scientific, but one based  upon symptoma-
tology is not  unscientific.   I  fully agree with
the  late Dr.  Fagge  that  the  " phenomena 
115
which are  commonly spoken of as symptoms
are part of the disease to which they belong, no
less  than the lesion or the specific cause or
whatever is taken as its  main characteristic."
To those who may think these remarks unnec-
essary, it is a sufficient reply that our knowl-
edge of the causes of several forms of miscalled
idiopathic anaemia dates from the  time when
Biermer substituted a significant  symptomatic
term for one that had nothing but vagueness to
recommend it.
  Nature of Pernicious Ancemia.—In placing
pernicious anaemia in the category of primary
anaemias, although  I do not regard it as  an
independent disease, I have  not been incon-
sistent.  An anaemia becomes pernicious when
the  blood  corpuscles  undergo  a  series  of
changes  which cause  them  to resemble, in
more than one respect, the corpuscles of the
amphibia.   Pernicious  anaemia  is  the  final
stage of several forms of symptomatic anaemia
and of chlorosis.   The prognosis of anaemia
per se is good until the changes in the blood
corpuscles above referred to are manifest.
  I cannot better explain my views  with refer-
ence to this affection than by  quoting  from an 
116
article that  I  contributed to the Philadelphia
Medical Times for April 3d, 1886.  " The most
interesting fact in  connection with the exami-
nation of the blood of pernicious anaemia, and
one to which, so far  as  I  know, attention has
never  been particularly  directed,  is  that  it
demonstrates a reversion  to the type of blood
found  in  the  lower  animals.   This  might be
justly regarded as a fanciful idea if it were based
upon a resemblance of the blood of pernicious
anaemia  to that of the  lower animals—birds,
fishes,  reptiles—in any  one particular; but  I
propose to show that the red corpuscles in this
disease approach those of  the lower animals in
many,  if not in all, of their  chief characteristics ;
namely, in their number, their size, their shape,
and the  amount of  haemoglobin they carry."
After   giving  some   details  concerning the
blood  corpuscles of the lower  vertebrate  ani-
mals and their percentage of haemoglobin,  I
continued as  follows:  " Turning  from these
interesting facts of comparative physiology  to
their bearing upon the  subject of this paper,
we observe in  well-marked cases of pernicious
anaemia:  1. A reduction in the number of the
red corpuscles  to a degree  that is normal in the 
117
cold-blooded animals. It is not at all uncommon
to find in this disease less than 1,000,000 corpus-
cles  per  cubic  millimetre.  My lowest  counts
have been  525,000  five  days  before  death;
560,000 in a case in which  recovery took place ;
and  315,000 a few hours before death.  In the
celebrated  case of  Quincke there  were  but
143,000 per  cubic  millimetre,  and yet  the
patient recovered.   Figures like these  are, as
has just been said, normal in the cold-blooded
animals.   2.  In pernicious anaemia the propor-
tion  of haemoglobin is often much greater than
normal.  It has been  observed  by  Laache and
others to be double the normal amount.   This,
in the opinion of the writer, is the most remark-
able feature  of this  disease, distinguishing it
from all other forms of anaemia, and  is  due to
the fact that—3, many, sometimes the majority,
of the corpuscles are greatly increased in size.
This is well  seen  in  the  accompanying cuts,
from photo-micrographs of diseased and normal
blood, made  for me by Mr. W. H. Walmsley,
of this city.  The photographs of the two speci-
mens were  made under precisely similar opti-
cal  conditions.  The  patient  furnishing  the
diseased specimen of blood is a typical case of 
 
119
pernicious anaemia, and is still under my obser-
vation.*
  " By applying the points of apair of compasses
to the enlarged corpuscles, it will be proved that
many of them  are at least double the normal
size.  4.  The corpuscles are not only increased
in diameter, but altered in shape, and have a
decided  tendency to assume an  oval outline.
So much so  that, in measuring  them  in  the
manner  indicated, we have to take into con-
sideration the direction in which the measure-
ment is made.  They have a long and a short
diameter."
  The specimen  from which  the  above  cut
was  taken  was not selected with the  view of
upholding this theory of reversion, but may be
regarded as typical  of the corpuscles of per-
nicious anaemia.  The enormous size of the cor-
puscles (megalocytes) and their altered shape
are still  better shown in a  cut  in the work of
Laache (Die Ancemie~), who had no theory of
reversion to maintain.
  From  the standpoint of the blood changes
and  of the  clinical history,  I contend that per-
nicious  anaemia is a condition  that may result
* He has since died. 
120
from a number of causes.  Prominent among
these is atrophy of the stomach.  In the Ameri-
can Journal of Medical Sciences, April, 1886, I
reported, in conjunction with Prof. Wm. Osier,
a typical  case of pernicious anaemia in which
the only special lesion was atrophy of  the mu-
cous membrane  of the stomach.  " This was
evident to the  naked eye  in the thin, cuticular
appearance, and  was abundantly confirmed by
the microscopical examination, which  showed
that the peptic  glands had been destroyed over
the greater portion of the organ."  About the
same time I had under observation another case,
a lady, whose symptoms  and blood changes
were identical with those of the above mentioned
case.  After an illness of more than a year she
died, and at the autopsy, at which I was present,
no lesion was  found to explain the profound
alteration of the blood.   According  to  most
authorities, the first of these cases in which a
lesion was found, to which the symptoms might
be reasonably attributed is, for that very reason,
not a case of pernicious anaemia.  The second
case, on the other hand, is a case of pernicious,
or " idiopathic,"  anaemia  because a lesion, to
which the symptoms might be attributed, was 
121
not found.  This appears to me to  be a very
unscientific  mode  of considering this subject.
Little by little, causes have been discovered suffi-
cient to account for all the symptoms of many
cases of idiopathic anaemia.   One of the latest
contributions of this sort has been that of Dr. Gus-
tav Reyher (Deulsches  Archiv fur Klin. Med.,
Bd. xxxix), who reports thirteen cases of profound
anaemia caused  by an  intestinal  parasite,  the
bothriocephalus  latus.   In all their  features,
these cases deserve the name of pernicious, and
had they  been fewer in number  and treated
in a different manner, the  anaemia might have
been considered "idiopathic," the presence of
a tapeworm in the intestine being regarded, in
a country  where this parasite is not uncommon,
as  a mere  coincidence.   The proof that  the
anaemia was secondary and parasitic was fur-
nished by the fact that,  in  every instance, a
wonderfully rapid recovery from an apparently
hopeless  condition  followed  the expulsion  of
the worm.   From such facts as these it is reason-
able to conclude that our ignorance concerning
the cause  of the most obscure  forms of perni-
cious anaemia, and our expression of that igno-
rance by the term "idiopathic," will gradually
disappear. 
122
  Having stated  above that I do not regard
pernicious anaemia as an independent disease,
some explanation is  needed of my reasons for
classifying it  under the head of primary anae-
mias.  I have none better than the one already
given by me  in the course of an  article in the
Medical News for July 3d, 1886:—
  " Opinions  are divided as to  whether  per-
nicious  anaemia is due to the operation  of a
cause (unknown) sui generis, or  to  the  pro-
longed operation of the ordinary causes of anae-
mia.  The  writer is  of the opinion  that the
varied clinical history of the different  cases on
record furnishes most decided evidence in favor
of the latter view.  Anaemia, once established,
tends to perpetuate  itself in  that species  of
vicious  circle of which so many examples are
furnished by  pathology.  Thus, to take an ex-
treme example,  the  epileptiform  convulsions
which immediately precede death from hemor-
rhage are  due to cerebral ischaemia, and this
very ischaemia is increased by the convulsions,
for experiments have shown  that the voluntary
muscles contain  a much greater amount  of
blood during  contraction than while at rest.  It
is quite  as essential to the blood-making organs 
123
as it is to the nerve centres that they be properly
supplied with blood, in order  that they may act
their  important part  toward  maintaining the
bodily health.   Doubtless there are  reserve
powers and compensatory activities in each and
all  of the blood-making  organs,  which  may
suffice to furnish a fair quality of blood under
the most adverse circumstances. These powers,
however, have their limit,  and, once exhausted,
the anaemia, instead of continuing ' simple,'
' functional,' or  ' symptomatic,' becomes' essen-
tial,' ' organic,' or ' pernicious.' "
  In short, I consider some forms of pernicious
anaemia to be due to malnutrition of the cyto-
genetic organs.
  Symptoms.—In the words of Coupland,  "the
symptoms of pernicious anaemia are those of
simple anaemia aggravated  and intensified."
In  well-marked cases the appearance  of the
patient is, to a certain extent, diagnostic.  The
lips and  palpebral conjunctiva are of a milky
white color and the skin of a lemon tint.   This
hue of the skin is characteristic, and at  once
gives rise to the suspicion of pernicious anaemia
to those who have seen one  or  more cases of
the disease.   It is unnecessary to enter at length 
124
into the symptoms of this affection which are,
for the  most part,  dependent  upon  want  of
oxygen. The chief of them are extreme muscu-
lar prostration, breathlessness and syncope on
slight exertion, or even in raising the head from
the pillow; and digestive disturbances, such  as
anorexia, nausea and vomiting, and constipa-
tion  alternating with diarrhoea.  Insomnia  is
more frequent thaji drowsiness until toward the
end, when somnolence gradually  deepens into
lethargy and coma.  Physical examination,  in
typical cases, reveals nothing but anaemic mur-
murs over the  heart, most distinct at the base
and the bruit de diable in the veins of the neck.
The  pulse  is usually rapid,  from ioo to  120.
The bones, particularly the sternum, are often
tender on percussion.  Retinal hemorrhages are
found in the majority of  cases.  The blood is
not only of the poorest quality, but is so small
in quantity that often a  drop is squeezed  with
great difficulty from a  deep puncture  in the
finger  pulp.  It resembles  serum more than
blood, and is aptly compared to water in which
beef has been washed.   On  examination  with
the microscope, the corpuscles present great
diversities in size  and shape.  The majority are 
125
often much larger than normal, and, compared
with normal corpuscles, are worthy of the name
of megalocytes.  Others are much  below the
normal size, and are  called microcytes; while
others are greatly distorted, being pear-shaped
for the most part, but sometimes biscuit-shaped,
hammer-shaped, or anvil-shaped.   These last
are known as poikilocytes.  The percentage  of
haemoglobin, owing to the increased size of the
corpuscles, is often as great as, or greater than,
normal, sometimes attaining twice  the normal
proportion.  This abnormal proportion of hae-
moglobin  is not always due  to  the increased
size of the corpuscles alone ; for, in some cases,
the blood  contains a large number of minute,
highly-colored  globules,  which  Eichhorst re-
garded as pathognomonic.  They are so minute
as to look like " small, red-tinged, fat globules."
These bodies are, of course, not counted in esti-
mating the number of the red corpuscles, and
yet their coloring matter contributes to the esti-
mate of the percentage of  haemoglobin.  The
corpuscles are, therefore, sometimes credited
with more coloring matter than they possess.
These minute colored bodies are  not always
present.   I have met with them in but one case, 
126
and Dr. Grainger  Stewart was unable to find
them in two well-marked and ultimately fatal
cases  which occurred in his practice.  Fever
of irregular type is certain  to occur  in late
stages  of pernicious anaemia.  It has  already
been spoken of among the symptoms of anaemia
in general.  An increased excretion of nitrogen
by the  kidneys  has been demonstrated in this
affection by Strumpell, and  is due to the inade-
quate supply of oxygen  to  the  tissues.  This
fact is of interest in connection with the exten-
sive fatty degeneration, which is sometimes the
only lesion detected in this disease.  " The fat
represents the non-nitrogenized remnants of the
decomposed albuminoids."
  Anatomical   Characters. — These   are the
changes in the blood itself and the consecutive
lesions in other tissues.  The former have been
already described and figured in the course of
this section   Of the latter, the fatty degenera-
tions of heart, intima of blood vessels, gastric
tubules, etc., are mentioned under the head of
anatomical characters  of anaemia in  general.
In  1875,  Prof.  William Pepper suggested the
marrow as the  source of the blood lesions  of
pernicious anaemia, and " described definite 
127
changes, chiefly of small, granular cells, in the
marrow of the radius and sternum in one case."
The marrow in this  case, the. first in which a
careful examination of this tissue was made, is
described as "decidedly paler than in health."
This is not the appearance of the hyperplasia
of the marrow, which  is regarded by some as
the fundamental lesion of this affection.   The
marrow is of a reddish purple color; its consist-
ence is increased;  its fat  cells have  disap-
peared, and the specific cellular elements of the
medulla have increased in amount. Frequently,
also, large numbers of nucleated red corpuscles
are found. These changes, interesting and sug-
gestive though they be, are by no means pecu-
liar to  pernicious anaemia and, when present,
are not primary.  They may be entirely absent,
as in a thoroughly studied case reported by Dr.
J. H. Musser, of Philadelphia.  They may also
be present in other diseases.  They were found
by  Litten in four cases of uterine carcinoma,
and by Orth in a case of carcinoma  recti, and
in another of  carcinoma  mammae.   (Berlin
Klin. Wochensch., xiv, 748.)
  Diagnosis.—In accordance  with the views
here presented, an  anaemia has entered  upon 
128
the pernicious stage when the blood corpuscles
are  greatly diminished  in  number — below
2,000,000 per cubic millimetre—and have under-
gone the alterations in  size and shape already
described and figured.  In addition, the per-
centage of  haemoglobin  may  be normal  or
above normal; certainly but  little below it in
any  case.  A  blood containing megalocytes,
poikilocytes and  microcytes, is the blood of
pernicious  anaemia.  This  condition may  be
secondary, i. e., the cause is known ; or primary,
i. e., the cause is, as yet, unknown.
  Prognosis.—The prognosis of pernicious anae-
mia is unfavorable, but  there are brilliant excep-
tions to this rufe ;  for example, those  furnished
by Reyher's cases.  These  were,   doubtless,
from an etiological standpoint, cases of parasitic
anaemia, but clinically they presented every
feature of pernicious anaemia.  In general terms,
when the cause is known and  removable,  the
prognosis is good; when known and not  re-
movable, it is  hopeless; when  unknown, it is
doubtful.
   Treatment.—Confining  what is to be said
about treatment to those cases  in  which  the
cause is unknown, the best  results have been 
129
attained by the use of arsenic, iron, and quinine.
Numerous undoubted cures have followed the
use of the first  of these drugs, which may be
given in pill or in Fowler's  solution.   Trans-
fusion has been attended with  little  or no suc-
cess, but  Dr. Oscar Silbermann reports  two
cases of profound  anaemia  which  recovered
after subcutaneous  injections  of defibrinated
blood.   The  blood was injected under strict
antiseptic precautions, and the quantity of each
dose varied from twenty to forty grammes.  In-
halations of oxygen  and the subcutaneous in-
jection  of quinine are  recommended by  Dr.
Henrot of Rheims.  Of equal importance with
drugs, is a nutritious diet, of which the digestion
may be assisted by malt and pancreatic  extract
or the food may be peptonized  before its inges-
tion.

            SECONDARY ANAEMIA.
  As already remarked on  a  previous page,
" Nearly every morbid  process, when it occurs
in a severe form, is sooner or later followed by
anaemia."  It is  therefore impossible, within the
limits of this work, to  consider every form of
secondary anaemia.  It  is also unnecessary, for
    I 
130
the differences between the various forms are
those of degree, not of kind.
  The anaemias of fever and hemorrhage have
already been considered.  That of syphilis has
been studied by Wilbouchewitch;  by Keyes, of
New York, and by Laache, of Christiania, and
it has been demonstrated that  the improvement
which follows the  administration of  mercurials
is accompanied with an increase in the number
and  value  of the red  corpuscles.  In the ad-
vanced stages of phthisis,  cancer, Bright's dis-
ease, and  cirrhosis  of the  liver,  the  blood
corpuscles are greatly reduced in number—be-
tween 2,000,000 and 3,000,000—and may assume
the characters—increased size  and altered shape
—of pernicious anaemia.

                TOXAN.EMIA.
  A poison may produce anaemia either directly
or indirectly.   The  ingestion of  arsenic  and
phosphorus, and the  inhalation of arseniureted
hydrogen are directly followed by the destruc-
tion of red corpuscles in  such quantities  that
haemoglobin appears in the  urine, and even
jaundice  (haematogenousl  may  ensue.   In
certain susceptible individuals the same symp- 
131
toms are caused by prolonged exposure to cold.
Other substances, such as potassium chlorate
and certain edible fungi, morchella and helvella,
esculenta, produce the same effects. For details
concerning these  and other agents destructive
to the red corpuscles, the reader is referred to
my article on " Haemoglobinuria," in " Wood's
Reference Handbook of Medicine." The action
of lead upon the  blood  corpuscles is probably
altogether indirect, through the marked disturb-
ances of digestion to which it  gives rise.  A
decided degree of anaemia in a case of chronic
lead poisoning should lead to a careful examina-
tion of the urine; for, as is well known, the long-
continued ingestion of lead is one of the causes
of cirrhotic kidney.
  The anaemia, if such it  can be called, pro-
duced by carbonic oxide poisoning, differs from
all other forms of toxanaemia.  This gas, when
inhaled, "displaces the oxygen  of the blood-
coloring matter, and takes its place, molecule for
molecule.  The combination thus formed is re-
markable for its stability, although, contrary to
what was formerly supposed, it can be displaced
by an indifferent gas or in a vacuum.  Its crys-
tals are isomorphous with  those of oxy-haemo- 
132
globin,  but have  a slight  bluish  tinge.  Its
spectrum is almost identical with that of O-hae-
moglobin,  but the  two absorption  bands are
moved  very  slightly nearer the violet end."*
The effect of this gas is to paralyze the red cor-
puscles which, until it is displaced, are incapable
of performing their functions.   The symptoms
of this form of toxanaemia are coma, with ster-
torous respiration, pallor  and coolness  of the
skin, while the  mucous membranes  are bright
red;  rigidity of muscles, dilated  pupils and
usually  a slow, easily-compressible pulse.  The
symptoms are, however, not uniform ;  for cases
are reported in which there was no  stertor, the
pulse was small and quick and the pupils con-
tracted.  Convalesence is apt to be very slow.
  In a case reported  by Dr. John  Graham  in
the " Transactions of the  College of Physicians
of Philadelphia," series iii, vol. viii, the patient,
a woman, aet. 74, was  not able  to sit up  until
seventy-three days after the accident.

             PARASITIC AN.EMIA.
  The parasites which have been thus far recog-
  * Article on Blood, in " Wood's Reference Handbook," by
F. P. Henry. 
133
nized as  causative of anaemia are the anchy-
lostomum duodenale, the bilharzia haematobia,
the filaria sanguinis, the bothriocephalus latus,
and perhaps, also, the plasmodium malariae.
  The  anchylostomum duodenale  was first
recognized by Griesinger, in 1854, as the cause
of  a profound  endemic anaemia, known  as
Egyptian chlorosis.  Since then it has attacked
the Italian laborers employed in the construction
of the St. Gothard tunnel, and has also prevailed
among brickmakers in Germany. The bilharzia,
first discovered  by Bilharz in Egypt, in 1851,
gives rise to anaemia by the haematuria  caused
by its presence in the body.  The adult animals
lie in dilated blood vessels in the  neighborhood
of  the bladder or other urinary outlet, and the
symptoms are due to the interference with the
circulation and the irritation caused by the ova
on their way to  the urinary passages.  The
filaria sanguinis causes anaemia  by interfering
with the lymphatic circulation.  The obstruction
to the lymph vessels may be  so great as to lead
to  their  rupture,  in which  event  the  lymph
escapes  from the body, usually with  the urine
(chyluria); sometimes, however, directly from
the integument, as in cases of lymph-scrotum. 
131
This parasite is quite common in certain tropical
and subtropical countries, especially in  China,
and has  recently acquired a new  interest from
the  discovery,  by  Dr.  John  Guiteras,   of
Charleston, S. C, that it is  indigenous to the
United States.*
  The plasmodium malariae  is the haematozoon
discovered by  Laveran  in Algiers.   It exists
within the red corpuscles and free in  the blood,
and is probably operative in  the causation  of
malarial  anaemia.   This  organism  has  been
studied  by  several careful observers;  in this
country particularly by Councilman,! of Balti-
more, and Osler.J of Philadelphia, although, to
quote the latter, " Laveran's  original descrip-
tion is well nigh  complete,  and subsequent
workers have done little else than confirm his
results, though to Marchiafava and Celli is due
the credit of insisting upon the amoeboid  char-
acter of the intra-cellular form."
 * Medical News, April ioth, 1886.
 f" Transactions  of the Association of American  Physi-
cians," vol. i.
 t British Medical Journal, March 12th, 1887. 
INDEX.
                                                      PAGES
Anaematosis.....................34, 69
Anaemia, predispositions to,.............16, 17
    senile,.......................   18
    congenital,....................   18
    from hemorrhage,................   22
    latent,.......................   25
    lightest grade of,..................   31
    highest grades of..................   33
    classification of,..................   46
    lymphatica, synonyms of,.............   59
        infective nature of,...............   65
        nature of,...................   69
        symptoms of,................   70
        diagnosis of...................   72
        prognosis of...................   73
        treatment of,.................   74
    splenica,.....................102
        anatomical characters of,............103
        clinical history of,...............106
        nature of,...................icg
        course and prognosis of,.......•.  .  .  . .  111
        diagnosis of...................112
        treatment of,................•.  113

Blood-plates,.....................    6

Chlorosis,......................   47
    confused ideas concerning,.............   51
    diagnosis of.....................   54
    prognosis of,....................   57
    treatment of,....................   58
Compte-globules of Malassez,  .............   11
Corpuscles, red,....................1,2
    white,.......................    4

Fibroadenia,......................104

Globinometer,.....................   14

                           135 
136
                                                       TAGHS
 Hemacytometer..................n, la
 Hxmatoblasts,....................     6
 Hacmic unit......................    54
 Haemoglobin,.....................     2
 Haycm's formula for intra-venous injection,.......    42
 Hematimclrc,.....................    11

 Lcucocrystallin,....................    85
 Lcncocyth.cinia,....................    75
     nomenclature of,..................    75
     anatomical characters of,..............    76
     retinal changes in,.................    81
     blood  changes in..................    82
     clinical history of,..........      .....    85
     pathogenesis of,..................    88
     lymphatic, a " myth,"...............    92
     xtiology of,....................    94
     dl-'-""MS of-....................    95
     prognosis of,....................    98
     treatment of,....................    99
 Leucocytosis,.....................    ?6
 beukosin........................    g4

 Microcytes,......................     7

 Parasitic anaemia....................132
 Pernicious araemia,..................II.
         nature of,...................nc
         symptoms of..................l2-,
         anatomical characters of,............126
         diagnosis of,..................,27
         prognosis of,.....;............I28
         treatment of,................       12g
 Poikilocytosis,.................           ,.
 Pseudochlorosis,..................'     ,0

 Schultze's granule masses,.............         6
 Secondary anaemia,..................   120

 Toxanaemia,...................        ,
•Transfusion,.......                                 ?_
                               .............    41 
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Landois'    Physiology.
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           By DR. EDOUARD MEYER,
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