E. A. (Edward Albert) Sharpey-Schäfer.

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^ Journ. Path, and Bacterial. , Edin. and London, 1893, vol. i. p. 434.
"^Arch.f. Physiol., Leipzig, 1887, S. 458.

2 Quoted by Gad, Ferhandl. d. Berl. 2ihys. Gesellsch., Arch. f. Physiol., Leipzig, 1887,
S. 584.

* Centralbl.f. Physiol., Leii^zig u. Wien, 1888, S. 261.

5 Com-pt. rend. Acad. d. sc, Paris, 11 Mai, 1896, p. 1072.

^ Arch, dephysiol. norm, et path., Paris, 1895, p. 711. "^ Ibid. p. 245.

8 Ibid., 1896, p. 159.

» Comp. rend. Soc. de. biol., Paris, 1896, p. 633.


fibrinogen, nucleo - proteid (prothrombin), and lime, and it would
appea^r probable from Pekelharing's researches that the two latter act
in combination, and in fact represent the body which was termed by-
Schmidt the fibrin ferment (thrombin). The reason why in the healthy
living vessels the iDlood does not coagulate, is, in all probability, that the
nucleo-proteid and lime have not entered into the necessary combina-
tion or interaction which enables them to act as a ferment upon the

Of the three factors above mentioned, it is certain that fibrinogen and
lime are both present in the plasma of circulating blood, and the problem
therefore resolves itself into the question whether nucleo-proteid is
present or not, or whether, if present, it is in a different condition from
that necessary to promote fibrin formation. We may consider the latter
question first, and in doing so it will be convenient to assume, as
the experiments of Pekelharing seem to have proved, that the fibrin
ferment of Schmidt is a product of the interaction of nucleo-proteid with
lime. This conclusion of Pekelharing's has, in fact, been confirmed by
the researches of Hammarsten, who has shown that the nucleo-proteid
(or prothrombin) which is obtainable from plasma is inactive as a ferment,
except in the presence of or after it has been exposed to the action of
soluble lime salts. It is not, however, equally clear that the fibrin
ferment is a compound of the prothrombin with lime, as Pekelharing
supposed it to be.

Is fibrin ferment present in the plasma of circulating blood ? As is
well known, Schmidt's fibrin ferment is ordinarily obtained from clotted
blood or from serum, and the ferment-like substance used by A.
Buchanan was also obtained by him from blood clot, and especially
from buffy coat, i.e. the portion containing most white corpuscles.
Schmidt found that if blood were drawm from the vessels direct into
alcohol, no ferment could be obtained from it.^ He came, therefore, to
the conclusion that the blood does not coagulate in the living vessels
owing to the absence of fibrin ferment, and that this is only formed or
set free when the blood is drawn. Since fibrin ferment could be obtained
in greatest abundance from the layer of the clot where leucocytes are
most abundant, and from other tissues and organs rich in similar cells, it
appeared probable that it is derived in drawn blood from the white
corpuscles, and, as Schmidt believed, from their disintegration. Such
disintegration of leucocytes was in fact described by Schmidt in drawn
blood, but the observation has not been generally confirmed. It is not,
however, necessary to suppose disintegration of the corpuscles, for they
may shed out the ferment without actually undergoing disintegration.
Now, conditions which render the blood incoagulable, such as injections
of " peptones," of snake venom, and nucleo-proteids in small amount,
greatly diminish the number of leucocytes in the blood. This they do,
however, not by causing the solution and disintegration of the corpuscles,

^ Hammarsten, Ztschr. f. physiol. Chem., Strassburg, 1896, Bd. xxii. We may dismiss
the hypothesis of Astley Cooper (Thackrah, "An Essay on the Cause of the Coagulation
of the Blood," Mccl.-Chir. Bev., Loudon, 1807, p. 191), which was revived by Briicke,
{Brit, and For. Med.-Cliir. Rev., London, 1857, and Virchow's ArcMv, 1857, Bd. xii.), that
the living vascular walls exercise by their presence a restraining action upon coagulation,
as having been sufficiently disproved by Lister ("On the Coagulation of the Blood,"
Proc. Hoy. Sac. London, 1863).

- Subsequent researches conducted in his laboratory have shown that a very small
amount is obtainable even under these conditions.


as supposed by Lowifc ^ and by Wright,^ but by causing their accumula-
tion witliin the tissues (? capillary blood vessels). For a very short
time after their almost complete disappearance from the blood they
begin gradually to reappear, and in one experiment C. J. Martin found
that the full number had reappeared within as short a time as fifteen
minutes.^ Moreover, if such disintegration really took place one would
expect the coagulability of the blood to be visibly increased, from the
setting free of their nucleo-proteids, whereas it is actually diminished
or abolished. Nevertheless, those substances, such as snake venom,
nucleo-proteids, and colloids, which in larger doses produce intravas-
cular coagulation, may in part act by causing disintegration, if not of
leucocytes at least of red corpuscles which also contain nucleo-proteids.
That this occurs to some extent is shown by the fact that the serum is
usually tmged by hemoglobin. And even without actual disintegration
the permeability of the corpuscles may become altered, and nucleo-
proteid shed out.

But there is another tissue upon which the reagent in question may
act, namely, the epithelial cells of the blood vessels. These are in all
probability composed of living protoplasm, and the reagents may either
cause them to shed out nucleo-proteid and so produce fibrin ferment,
or, by deleteriously affecting them, may cause them to react upon the
leucocytes which are passing along in contact with their inner surface,
and effect a discharge of nucleo-proteid from these cells. That snake
venom affects the blood vessels deleteriously is shown by the capillary
haemorrhages which are so frequently seen after poisoning by it, and
by the rapid effect it produces on the blood circulating in the mesentery,
if a little be applied to the surface of that membrane.'^ The same does
not, however, obtain with artificial colloids, nor with nucleo-proteids ;
although, with partial blocking of the portal vein, after injection of a
small dose, capillary haemorrhages have been found to occur in the liver.^

The e"vddence which we have had before us points to the following
conclusions regarding coagulation : —

1. That the coagulation of blood, i.e. the transformation of fibrinogen
into fibrin, requires for its consummation the interaction of a nucleo-
proteid (prothrombin) and soluble lime salts, and the consequent produc-
tion of a ferment (thrombin).

2. That either nucleo-proteid is not present in appreciable amount
in the plasma of circulating blood, or that the interaction in question is
prevented from occurring within the blood vessels by some means at
present not understood.

3. That the nucleo-proteid (prothrombin) appears and the interaction
occurs, as soon as the blood is drawn and is allowed to come into contact
with a foreign surface, the source of the nucleo-proteid being in all
probabiHty mainly the leucocytes (and blood-platelets ?).

4. That, under certain circumstances and conditions, either the
nucleo-proteid does not appear in the plasma of drawn blood, or it
appears, but the interaction between it and the lime salts is prevented
or delayed.

\ "Stud. z. Physiol, w. Path. d. Bhites," Jena, 1892.
^ Proc. Roy. Soe. London, 1893. vol. lii.
^ Loc. cit.

■^ Weir Mitchell and Reichert, " Researches upon the Venoms of Poisonous Serpents,"
Sm/ilhson. Contrih. Kwnol., Washington, vol. xxvi.

"^ Wooldridge, Trans. Fulh. iSoc. London, 1888, ]>. 421.


5. That the nucleo-j)roteid (prothrombin) appears in the plasma of
circulating hlood under certain conditions, being in all probability shed
out from the white corpuscles and blood platelets, or in some cases even
from the red corpuscles ; and that when shed out under these conditions
from the corpuscles, or when artificially injected into the vessels, it
tends at once to interact with the lime salts of the plasma and to
form fibrin ferment (thrombin), intravascular coagulation being the

6. That, under other conditions, either the shedding out of nucleo-
proteid from the corpuscles, or its interaction with the lime salts of the
plasma, may be altogether prevented and the blood rendered incoagulable,
unless nucleo-proteid be artificially added, or unless a modification of
the conditions is introduced which will permit of the interaction of
the nucleo-proteid with lime to form ferment.

7. That the nucleo-proteid (prothrombin) is incompetent, in the
entire absence of lime salts, to promote the transformation of
fibrinogen into fibrin ; but, as a result of its interaction with lime
salts, it becomes transformed into a ferment (thrombin), which,
under suitable conditions of temperature and the like, produces

8. That either the place of nucleo-proteid in coagulation may
be taken by certain albumoses, such as those found in snake venom,
and by certain artificial colloidal substances, such as those prepared
by Grrimaux, or that such substances may act by setting free nucleo-
proteid from the leucocytes and other elements in the blood, or
from the cells of the blood vessels, and thus indirectly promote

If the former supposition is the correct one, in all probability these three
substances (nucleo-proteid, snake venom, albumose, and colloid of Grimaux)
contain the same active molecular group. ^^

Lymph, Chyle, Seeous Fluids, Cerebro-Spinal Fluid, Synovia.

Lymph, which is obtainable from the lymphatic vessels of the limbs,
from the thoracic duct, and from the lacteals in the intervals of absorp-
tion of digestiA^e products, or from the serous cavities — although only
occurring normally in sufficient amount for purposes of analysis and
experiment in the pericardial cavity — resembles generally in the char-
acter of its constituents, but not in their relative amount, the plasma of
the blood. Nor are the proportions of its constituents so constant as are
those of blood plasma, for there is reason to believe that the lymph from
different organs presents very considerable differences in their relative

Lymph has generally been obtained for analysis from accidental
lymphatic fistulai in man, from experimental fistulse in large animals,
such as the horse, or from the thoracic duct of fasting animals (dog).
The amount flowing along the thoracic duct is about 64 c.c. per kilog.
body weight per diem.^

^ Halliburton and Pickering, op. cit.

2 R. Heidenhain, Arch. f. d. ges. Physiol., Bonn, 1891, Bd. xlix. S. 216; Noel Paton,
Journ. Physiol., Cambridge and London, 1890, vol. xl. p. 109.


The following analysis is given by J. Munk and Eosenstein from
case of fistula of the thoracic duct in man : ^ —

In 100 parts lymph —
Total solids
Proteids .

Substances soluble in ether




3 -7-5 -5


Hensen and Danhardt ^ found the following inorganic constituents : —

In 100 parts lymph-
CO, "





They obtained only Q-l per cent, of fibrin (as compared with 0-4 per
cent, in blood plasma). This is perhaps the reason why the intravenous
injection of peptone in small amount or at a slow rate may, as noticed
by L. E. Shore,^ prevent the clotting of the lymph but not that of the
blood. The experiments of Spiro and Ellinger* seem, however, to
indicate that, under the influence of peptone, an anti-coagulating
substance is formed in lymph, and from this passes into the blood.
The other proteids are also present in much less amount, but the relative
proportion of albumin to globulin is almost exactly maintained. As
already stated (p. 162), the present proteid quotient is fairly constant in
the same individual, both for blood serum, lymph serum, and serous
effusions.^ Lymph generally contains more urea than does the blood of
the same individual. Thus in a dog Wurtz found —

In the blood, 0-009 parts per cent, of urea.
In the lymph, 0-016 ,, ,, ,,

The amount of sugar in lymph is about the same as in blood plasma,
although, if dextrose be injected into the blood vessels, it soon appears in
greater proportion in the lymph than in the blood.*^ Lymph contains
a distinct amount of glycogen, but this substance is wholly contained in
the corpuscles, and none exists in the plasma.'^

The aqueous humour is a form of lymph, and contains the same pro-
teid substances as lymph, namely, fibrinogen, serum globulin, serum
albumin, and similar extractives and salts.^ It contains no corpuscles,

1 Arch. f. Physiol., Leipzig, 1890, S. 376 ; Virchoiv's Archiv, 1891, Bd. cxxiii. S. 230
(contains a historical account of other cases).

^ Virchmv^s Archiv, 1866, Bd. xxxvii.

^ Journ. Physiol., Cambridge and London, 1890, vol. xl. p. 561.

■* Ztschr.f. iJhysiol. Chem., Strassburg, 1897, Bd. xxiii. S. 121.

•'■' Salvioli, Arch. f. Physiol., Lei])7Ag, 1881, S. 269; Hofmann, Arch. f. cxper. Path.
V,. Pharmakol., Leipzig, 1882, ]3d. xvi. S. 135.

^ The reasons for this will be considered in the article on " Ljmiph Production."

"^ Dastre, Compt. rend. Acad. d. sc, Paris, 1895, tome cxx.

^ Halliburton and Friend, Pep. Brit. Ass. Adv. Sc, London, 1889.



and does not clot spontaneously, but only on addition of fibrin ferment,
such as is contained in serum. Traces of urea are present but no sugar,
although a slight reduction of Fehling's solution is sometimes obtainable.
This is probably due to paralactic acid.^

The following analysis of aqueous humour is by Lohmeyer : ^ —

In 1000 parts-
Water . . . . 986-87



Other salts


Pericardial fluid is a form of lymph which is found in small
quantity within the sac of the pericardium. Peritoneal and pleural
fluids, and the fluid of the tunica vaginalis, are not normally present in
sufficient quantity to be collected and analysed. Pericardial fluid
contains rather less proteid than ordinary lymph (2-28-2-55 per cent.).^

Pericardial fluid, as obtained from the horse or ox, is a yellowish
fluid, resembling serum in appearance and in its general composition,
but it contains fibrinogen.^ It usually has no leucocytes, nor is it
spontaneously coagulable, but it coagulates on the addition of ferment or
of nucleo-proteid.

Chyle has nearly the same composition as lymph, but it contains
more solid matter, the increase being chiefly in fats, but also in proteids.
The following table from Hoppe-Seyler gives its general composition in
the dog and a comparison with the serum of the same animal.

Chyle of Serum of

Dog. same Dog.

Water .... 90-67 93-60
Pibrin .... 0-11

Albumin and globulin . . 2-10 4-52

Pat, lecithin, cholesterin . 6-48 0'68

Other organic substances . 0-23 0-29

Salts .... 0-79 0-87

The ether extract of chyle was found by Hoppe-Seyler to contain,
per cent. : —

Cholesterin . . . .14-09

Lecithin . . . . 8-84

Pats ..... 77-07

There is also, according to Hoppe-Seyler, a small amount of soap in
chyle. The amount of urea and of sugar is about the same as in lymph.

The cerebro-spinal fluid, although resembling lymph in its appear-
ance, and probably in being formed by transudation from the blood
vessels, differs from lymph chemically in certain important details.
Although cerebro-spinal fluid is not obtainable normally in sufficient
amount for analysis, the fluid of a meningocele appears to be nothing
but an accumulation of the normal fluid, and has been frequently
analysed, and the fluid of hydrocephalus has also been used for this
purpose. Cerebro-spinal fluid as thus obtained is a clear, colourless

1 Kuhu, Arcli.f. d. ges. Physiol., Bonn, 1888, Bd. xi. S. 200 ; Griinhagen, ihid., S. 377.

" Gorup-Besanez, "Lehrbuch," 1878, S. 401.

=* Hoppe-Seyler, "Physiol. Chem.," 1881, S. 605.

* For analyses of pericardial fluid from the horse, and also for the analj^sis of various
dropsical fluids which tend to accumulate in the serous cavities of man, see Halliburton,
"Chem. Physiol.," pp. 338 and 339, and Brit. Med. Journ., London, 1890.


liquid of specilic gravity about 1007-8, and of a faintly alkaline reaction.
It contains only about 1 per cent, of solids, chiefly inorganic salts, of
which the greater part is sodium chloride, the other salts being potas-
sium chloride, phosphates of lime and magnesia, and traces of iron and
sulphates.^ There is, as a rule, not more than 1 part per 1000 of
proteids. These consist almost entirely of proteoses ; chiefly in the form
of protoalbumose, which is precipitable by saturation with sodium
chloride or magnesium sulphate. There is also a very small amount of
serum globuhn, but no serum albumin or fibrinogen, nor is there any
nucleo-proteid or fibrin ferment. Earely peptone occurs.

In addition to proteids and traces of nitrogenous extractives, there is
present in cerebro-spinal fluid a non-nitrogenous substance peculiar to it,
which has the property of reducing copper salts when heated with them
in an alkaline solution. This was thought by Claude Bernard to be
sugar. The substance, however, is not sugar, being non-fermentable,
non-rotatory, and incapable of combming with phenylhydrazin to form
a crystalline compound. According to Halliburton, it is pjTOcatechin,
and has the formula 0^11^(011)2, being probably one of the decomposi-
tion products of proteids ; it occurs in traces in the urine. In tapped
cases of hydrocephalus and meningocele the amount of this substance
increases after the first tapping.^

The presence of proteoses, and occasionally of peptones, in the cerebro-spinal
fluid, although these substances do not occur in blood or lymph, is of interest
in connection with the theory of Gaskell, Avhich supposes the central nervous
system of vertebrates to have become developed in connection with a dorsal
alimentary canal, such as is found in arthropods. ^ N'o digestive ferment
(pepsin, trypsin) has, however, been detected in cerebro-spinal fluid.

Synovia differs from lymph in containing a larger amount of solids
and also a mucin-like substance. Mucin, according to Landwehr,'^ yields
a reducing sugar on boiling with mineral acids, but, according to Ham-
marsten,^ this mucin-like substance of synovia does not yield such
reducing sugar, and is of the nature of nucleo -albumin (containing 5 per
cent, of phosphorus).^ But the mucin-like material obtained by
Salkowski^ from synovia neither yielded phosphorus nor did it give
any reducing sugar.

Salkowski gives the following as the composition of the synovia
analysed by him : —

In 100 grms.— Water .... 93 '084

„ Mucin-like substance
„ Other proteids

. 4-824)''-^'^^



„ Lecithin ,

. 0-017

„ Cholesterin

. 0-569 8

„ Inorganic salts

. 0-849 (Nacl 0-772)

^ Yvon, quoted by Halliburton.

2 For further details consult Halliburton, " Cliem. Phj'siol.," p. 355 ; also "Report
of Spina Bifida Committee," Trans. Clin. Soc. London, vol. xviii. ; and journ. Physiol.,
Cambridge and London, vol. x. p. 232, where the previous literature will be found.

" Address to the Section of Physiology, Pep. Brit. Ass. Adv. Sc, London, 1896.

■' Arch./, d. ges. Physiol., Bonn, Bd. xxxix. S. 193.

^ Jahrcsh. il. d. Fortschr. d. Thier-Cliem., Wiesbaden, Bd. xii. S. 484.

''For analysis of synovia by different observers, see Halliburton, " Chem. Physiol.,"
p. 351.

^ Virchoid's Archiv, Bd. cxxxi. S. 304.

^ This is unquestionably abnormally high. The fluid was from a case of chronic coxitis.


By Akthuk Gamgee.

Contents. — Distribution in tlie Animal Kingdom, p. 186 — Relations to other Con-
stituents of Red Corpuscles, p. 188 — ^Arterin ? and Plilebin? ]), 190 — Oxyhae-
moglobin, p. 193 — Methods of obtaining, p. 194 — ^Composition of, p. 197 —
Crystalline form, p. 203 — Action of Reagents on, p. 207 — Spectrum, p. 208 —
Spectrophotometry, p. 213 — Photographic sjjectrum, jj. 225 — Haemoglobin, p.
229 — Prej)aration of, Tp. 232 — Colour and Spectrum, p. 233 — Compounds with
Gases, p. 237 — Derivatives and Products of Decomposition, p. 243.

By the term hfemoglobin ^ is designated the highly complex, iron-con-
taining, crystalline colouring matter, which forms the most important
constituent of the coloured corpuscles of the hlood,^ and in virtue of
which they perform their function as the oxygen-carriers of the
organism. This body possesses the remarkable property of linking
to itself a molecule of oxygen, so as to form an easily dissociated
compound, which is termed oxyhasmoglobin, to distinguish it specifically
from the colouring matter which has parted with its dissociable
oxygen ; for the latter some retain the name hcemoglohin, though
it is commonly, and by English writers usually, distinguished by
the term reduced hcemoglobin.

Both oxyhsemoglobin and reduced luTemoglobin invariably (Hlifner)
exist side by side in varying proportions in the living blood ; the
former being most abundant in arterial, the latter in venous, blood.
In the present chapter the term haemoglobin will be generally employed
when speaking of the blood-colouring matter, without specific reference
to its relation to oxygen ; the term reduced hcemoglobin being invariably
employed when reference is made to the colouring matter, deprived of
its dissociable, or, as we may term it, in consideration of the part which
it plays in the organism, its res'piratory oxygen.

Should we speak of " hsemoglobin " or "the heemoglobins," of
" oxyhsemoglobin " or "the oxyheemoglobins ? "— In a subsequent
section, it will be shown that the blood-colouring matter is by no
means absolutely identical in all animals, but that it exhibits con-
siderable variations in certain physical characters, and in chemical

■^ Hoppe-Seyler, to Avhom we owe a joreat part of our knowledge of the blood-colouring
matter, first suggested this term. "Um Verwecliseluugen zu vermeiden nenne ieli das
Bhitfarbstoff ' Hsemoglobulin oder Hsemoglobin,' " Virchow's Archiv, lS6i, Bd. xxix. S.

^ Hsemoglobin constitutes about 40 "4 per ceut. of the weight of tbe moist corpuscles,
and about 95 '5 per ceut. of all the organic substances coutaiued iu them.


composition, according to the species of animal from which it has
been derived. Based upon these facts, or perhaps in order to emphasise
them, it is now customary with German writers, following the example
of Hoppe-Seyler, to speak, not of " oxyha?.moglobin," but of " the
oxyhgemoglobins," of " the haemoglobins " and not of " hi3emoglobin."
This appears to me to be an unnecessary and misleading attempt to
attain accuracy in scientific terminology, at the expense of true and
philosophical conceptions. As will be shown in the sequel, the
proportion in which iron, the characteristic element in the blood-
coloming matter, occurs, is absolutely the same in many animals, the
weight of the molecule being probably identical in these cases. There
is further abundant evidence in favour of the view that the typical
nucleus, upon which the optical and physiological properties of haemo-
globin depend, is absolutely identical in all animals. The grounds
for this assertion will be given in the sequel, when it will be shown
that the opinion advanced of recent years, as to the existence of
several hfemogiobins, not only varying in composition, but possessed
of different powers of combining with oxygen, rests upon undoubted


After the discovery by Hoppe-Seyler ^ of the characteristic spectrum of
haemoglobin, had enabled him definitely to prove that this substance is the
true blood-colouring matter, Kiihne ^ showed that the same body is the cause
of the red colour of the voluntary muscles of vertebrates. Hunefeld^ and
Eollett * had shown that the blood of the earth-worm and of Cliironmous
yielded crystals identical with the blood crystals obtained from other animals ;
and Eay Lankester ^ and ISTawrocki ^ simultaneously established the fact that
these crystals consisted of haemoglobin, by examining their spectroscopic

Online LibraryE. A. (Edward Albert) Sharpey-SchäferText-book of physiology; (Volume v.1) → online text (page 26 of 147)