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secretion, obtained from temporary fistulse in dogs, and our conclusions
are summarised as follows : —

1. The pancreatic juice obtained from temporary pancreatic fistulfe,
from dogs, produces a change in the caseinogen of milk.

^ The nutritive value of casein is given by Marcuse {Arch. f. d. cjcs. Physiol., Bonn, Bd.
Ixii. S. 223) as equal to that of meat proteids.

^ E. Salkowski {Virchoivs Archiv, Bd. cxliv.) states that caseinogen, if not coagulated in
the process of preparation, is completely digested by gastric juice, if a sufficient volume of
the latter is employed, e.g. 500 parts of gastric juice to 1 of caseinogen.

^ Sebelien, Ztsclir. f. physiol. Chem., Strassbm-g, Bd. xx. ; Popoff, ihid., Bd. xviii. ;
Gumlich, ibid., Bd. xviii. ; Weintrand, Verhandl. d. -physiol. Gesellscli., Arch. f. physiol.,
Berlin, 1895; Clara Willdenow, Inaug. Diss., Bern, 1893 ; W. Sandmeyer, Ztschr. f.
physiol. Ohem., Strassburg, 1895, Bd. xxi. S. 87. "^ Loc. cit.

^ Preisschrift, Rostock, 1894. ® Loc. cit.

"^ Ztschr. f. physiol. Chem., Strassburg, 1896, Bd. xxii. S. 103.

8 Virchoiv's Archiv, 1896, Bd. cxlv. S. 30.

^ Journ. Physiol., Cambridge and London, 1896, vol. xx. S. 97.

^^ Verhandl. d. naturh.-vied. Ver. zu Heidelberg, IST. P., BJ. iii. S. 3.

" Proc. Roy. Soc. London, 1879 and 1881.

^^ Journ. Physiol., Cambridge and London, 1891, vol. xii. p. 193.

13 Ibid., 1892, vol. xiii. p. 469. " Vol. ii. p. 446.



138 THE CHEMISTRY OF THE TISSUES AND ORGANS.

2. This action differs from the action of rennet in the following
particulars : —

(«) The precipitate of casein occurs in the warm bath (35°-40° C.)
in the form of a finely granular precipitate, the milk to the naked eye
undergoing no change in its fluidity. On coohng this to the temperature
of the air, it sets into a coherent curd which contracts to only a small
extent, and is again broken up into fine granules by warming to 35° C,
the milk to the naked eye becoming again fluid. This may be repeated
a great number of times.

(b) This phenomenon is not prevented, but only slightly hindered, by
such an addition of potassium oxalate as completely inhibits the activity
of rennet.

3. The experiments performed with extracts of the gland lead to
similar results, which may be masked if the action of the tryptic ferment
is very energetic.

4. The precipitate produced may be provisionally termed jMncrecdic
casein. By the action of rennet it can be converted into true casein.
Its solubilities, as summarised in the following table, are partly like
those of caseinogen, partly like those of casein. It is probably some-
thino; intermediate between the two.





(a) Caseinogen.


(fi) Casein.


(c) Pancreatic Casein.


{a) Inwater + CaCOg


Soluble.


Insoluble.


Insoluble.


(6) In lime water .


Soluble ; precipitable


Soluble ; precipitable


Soluble ; precipitable




with difficulty by


with ease by CaClo ;


with ease by CaCU ;




CaClo.


precipitate pro-


precipitate pro-






duced by trace of


duced by ti'ace of






CaClg at40°, soluble


CaCla at 40°, not






on cooling.


soluble on cooling.


(c) The precipitate


Soluble in 5 per cent.


Insoluble in 5 per


Slightly soluble in 5


produced by add-


NaCl.


cent. NaCl.


per cent. NaCl.


ing CaCU to (&)








{d) Lime water solu-


Converted into casein


So readily precipitable


Behaves like casein-


tion.


by trace of phos-


by trace of calcium


ogen.




phoric acid and


salts that the action






rennet.


of rennet could not
be iiroperly tested.




(c) In 0"5 sodium


Soluble ; precipitable


Soluble ; precipitable


Soluble ; precipitable


bicarbonate solu-


with ease by CaCU ;


with difficulty by


with ease by CaClo ;


tion.


precipitate pro-


CaClg.


precipitate pro-




duced by trace of




duced by trace of




CaClg at 40°, dis-




CaClo at 40° C, not




solves on cooling.




soluble on cooling.



The casein and caseiriogen of human milk. — The facts described up
to the present point are derived from experiments on cows' milk.
There are very important differences between this and the principal
proteid of hmnan milk. A large number of investigators ^ have noted
such differences as a more finely subdivided and more easily digestible
clot formed by rennet, but the difference between the two proteids goes
deeper than that. TJuman caseinogen is more difficult to precipitate by
acids (and is easily soluble in excess) and by salts; it often will not

1 Bredert and Schroter, Ccntralbl. f. agric. Chem., Leipzig, 1888; Biedert, " Untersuch.
u. d. cliem. Unterschiede der Menschen und Kuhniilch," Stuttgart, 1884 ; Langgaard,
Virchow's Archiv, Bd. L\v. ; Makris, Inaug. Diss., Strassburg, 1876.



THE PROTEIDS OF MILK. 139

clot with rennet at all; when it does so, the clot is a flocculent
precipitate, which frequently redissolves rapidly in excess of gastric
juice. According to Szontagh,^ human caseinogen yields no pseudo-nuclein
on gastric digestion ; this was confirmed by Wroldewski,^ who found
also that human caseinogen has the following percentage composition —
C, 52-24; H, 7-31; N, 14-9; P, 0-68; S, 1-117; 0, 23-66. This, it will
be seen, is different from the composition of the caseinogen of cows' milk.
Human caseinogen contains phosphorus, but not in the form of pseudo-
nuclein, as in cows' milk.

Wroblewski finds that human milk contains small quantities of lact-albumin,
and of another proteid very rich in sulphur (4-7 per cent.) and poor in carbon
(4.5-01 per cent.). Lehmann and HempeP find that the caseinogen of cows'
milk contains 7"2 per cent, of ash; this consists of CaO, 49-5; MgO, 2-4;
PoO-, 47 -0; and SO3 1-06 per cent. The elementary composition of the
proteid is given as C, 50-86 ; H, 6*72 ; N, 14-63 ; P, 0-81 ; S, 0-72 ; ash, 6-47
per cent. The caseinogen of woman's milk contains more sulphur, 1-09, and
less ash, 3-2 per cent. Some of the differences between the two caseinogens
are doubtless dependent on the amount and nature of the ash with which they
are associated.

The occurrence of nucleon (phospho-carnic acid) in milk has ah'eady been
mentioned on p. 104. Siegfried '^ states that the nucleon accounts for 41-5 per
cent, of the phosphorus in human milk, but for only 6 per cent, of that in
cows' milk. Practically all the phosphorus in human milk is in organic com-
bination (nucleon and caseinogen).

Lad-albumin. — After the precipitation of caseinogen and lacto-
globulin by half- saturation with ammonium sulphate, lact-albumium re-
mains in solution. It can be incompletely precipitated from this solution
by saturation with sodium sulphate. It is completely precipitated with
the other proteids when milk is saturated with ammonium sulphate. It
coagulates between 70° and 80° C. ; in cows' milk at 77° C. It is not
separable, like serum albumin and egg albumin, into several proteids by
fractional heat coagulation. It, moreover, is coagulated by heat very
slowly; the solution must be kept some hours at 77° C, before it is
completely precipitated. Its specific rotatory power ^ a^-= -36°, -i.e. less
than that of serum albumin ; it has the following percentage composi-
tion : C, 52-19; H, 7-18; N, 15-77; S, 1-73; 0, 23-13. The high
percentage of sulphur is another distinction between it and serum
albumin.

Ladoglobulin. — A trace of globulin is obtained from cows' milk by
saturating it with magnesium sulphate, after the removal of the
caseinogen by saturation with sodium chloride (Sebelien). Its
characters are like those of serum globulin. The amount of globulin in
colostrum is considerable, but in fully-formed milk it is present in so small
an amount that for a long time I was unable to confirm Sebelien's state-
ment. Hewlett,^ however, who worked with me, confirmed its presence.

^ Uiigar. Arch. f. Med., Wiesbaden, Bd. i. S. 192 ; Jaliresh. il. d. Fortschr. d. Thier-
Cliem., Wiesbaden, Bd. xxii. S. 168.

^ Inaug. Diss., Bern, 1894. See also Moraczewski, Ztschr. f. physiol. C'hem., Strassburg,
1891, Bd. XX. S. 28.

^Arch.f. d. ges. Physiol., Bonn, Bd. Ivi. S. 558.

■* Ztschr. f. physiol. C'hem., Strassburg, 1897, Bd. xxii. S. 575.

^ Sebelien, Jahresb. it. d. Fortschr. d. Thier-Ohem., AViesbaden, Bd. xv. S. 184.

® Journ. Physiol., Cambridge and London, 1892, vol. xiii. p. 798. See also Arthus, Arch,
de physiol. norm, etpath., Paris, 1893, p. 673,



I40 THE CHEMISTRY OF THE TISSUES AND ORGANS.

Kemmerich ^ stated that casein (i.e. caseinogen) is formed at the cost of
the albumin of milk after secretion. He estimated the caseinogen by pre-
cipitating it with dilute acetic acid, the precipitate being subsequently freed
from fat by ether, dried and weighed. He estimated the albumin by weighing
the heat coagulum after separating out the acetic acid precipitate, and he found
that, after the milk is alloAved to stand some hours at the body temperature,
the caseinogen increases in quantity, and the albumin diminishes. Dahnhardt ^
claimed to have separated out from the cells of the mammary gland a ferment
soluble in glycerine which hastens this process.^

These experiments are quoted with approval by Heidenhain,^ but do not
seem to have been followed up recently by the more precise methods of
modern inilk analysis. The differences noted by Kemmerich are nsnally small,
and might be well within the limits of experimental error.^ They date from a
time when lact-albuniin was considered to be identical with serum-albumin,
and when caseinogen was looked upon as nothing more than alkali-albumin.
Among other statements made by Kemmerich is the one that lact-albimiin is
converted into casein by boiling — an assertion which is quite sufficient to show
the somewhat crude notions prevalent at the time concerning the proteids of
milk. The dominant idea of these workers appears to be to account for the
milk-proteids as simple derivatives of the blood proteids.

In the foregoing account of milk, no description of analytical processes has
been given. For the numerous methods which may be used in this highly
technical branch of analytical chemistry, the reader is referred to text-books
on that science.

^ Arcli.f. d. ges. Physiol., Bonn, 1869, Bd. ii. S. 401.

'^ Ibid., 1870, Bd. iii. S. .586.

^ J. C. Lelimann considered that caseinogen is formed from albumin by weak alkali
{Centrcdbl. f. d. med. Wissensch., Berlin, 1864, S. 530).

* Hermann's "Handbuch," 1883, Bd. v. S. 395.

^ That this explanation is probably correct, is shown by some experiments of Schmidt-
Millheim {Arch.f. d. ges. Physiol., Bonn, 1882, Bd. xxviii. S. 243) and Thierfelder [iUd.,
1883, Bd. xxxii. S. 619), who, by using the same methods, found a slight diminution of the
casein after milk had stood some hours at the body temperature. Schmidt-Mitlheim sup-
posed that on standing some of the casein is converted into peptone.



THE BLOOD.

By E. A. SCHAFEK.

Contents :— General Properties, p. 141 — Amount, p. 141 — Colour, p. 142 — Specific
Gravity, p. 143 — Reaction, p. 144 — Coagulation, p. 145 — Relative Amounts of
Plasma and Corpuscles, p. 147 — Number of Corpuscles, p. 149 — General Com-
position of Blood, p. 153 — Composition of Blood Corpuscles, p. 155 — Composi-
tion of Plasma, 23. 156 — Proteids of Plasma, p. 161— Theories of Coagulation,
p. 168 — Causes of Coagulation, p. 178 — Lymph and allied Fluids, p. 181.

The blood is a red Huid of alkaline reaction ; in man its specific gravity
is about 1'060. It has an odour which is different in different species
of animals, and is brought out by the addition of sulphuric acid. It
sets more or less rapidly into a solid clot or coagulum after death, or on
removal from the living blood vessels. It consists of a clear, yellowish
liquid, the plasma or liquor sanguinis, and of microscopic particles or
corpuscles of two kinds : the one kind, less numerous, termed the white,
or colourless, or lymph corpuscles (leucocytes) ; the other kind, by far
the most numerous, the red, or coloured corpuscles (erythrocytes),
which give the blood its characteristic tint. In addition to these, a
variable number of much finer discoid colourless particles (elemen-
tary particles, blood-platelets) are apparent in a microscopic preparation
of drawn blood.

Amount. — The amount of blood in the body was determined in the
following manner by Welcker : ^ — A measured sample of blood is drawn,
and, after being defibrinated, portions of it are diluted to different degrees
to serve as samples of comparison. The rest of the blood is then collected
and defibrinated, and the vessels are washed out with salt solution until
the washings are colourless : they are all added to the defibrinated blood,
which is now diluted with water until it corresponds in tint with one of
the above samples, the dilution of which is accurately known. The total
quantity of blood in the vessels can then be calculated. In order to
obtain every trace of blood, Welcker further minced up the whole
animal and extracted the tissues with water, adding this to the mass
of blood. Some hsemoglobin would thereby, however, be yielded by the
muscles (Kiihne).

The amount has also been determined during life by the method
of Glrehant and Quinquaud,^ who allowed an animal to inspire a

^ Ztschr. f. rat. Med., 1858, Ser. 3, Bd. iv. S. 147. Welcker's method is improved
by combining the hcemoglobin with carbonic oxide gas (Gescheidlen).

^ Compt. rend. Acad. d. sc, Paris, 1882, tome xciv. p. 1450 ; Journ. dc I'anat. ct
physiol. etc., Paris, 1882, No. 6, p. 564.



142 THE BLOOD.

measured amount of carbonic oxide (mixed with oxygen) ; then drew
off a measured quantity of blood, and determined the amount of carbonic
oxide this contained ; the amount in the whole of the blood in the body
would be in the same proportion, and the quantity of blood could thus
be calculated. The result arrived at by these two methods is that the
blood is equal to one-eleventh to one-fourteenth of the body weight
(about 5i kilos, in a man of 70 kilos.).

Colour : laking of blood. — The colour of the blood varies in different
parts of the vascular system. The differences are dependent upon the
amount of oxygen in combination with the hcemoglobin. The colour
also becomes altered by any reagent or circumstance which tends to
cause the haemoglobin to pass out from the corpuscles into the circum-
jacent fluid. When this is brought about, the blood loses its opaque
appearance and becomes transparent and of a laky tint. Such " laky "
blood is readily produced by the addition of distilled water, and also by
water holding neutral salts in solution up to a certain percentage ; which
percentage varies for different salts, and also, with the same salts, for the
blood of different animals. A solution containing just such a percentage
of salt as suffices to keep the corpuscles unaltered in form, and without
removal of any of their heemoglobin, is " isotonic " ; ^ solutions below and
above such strength are respectively " hypisotonic " and " hyperisotonic." ^
For human blood, a solution of common salt is isotonic with a percentage of
0"9 ; for defibrinated ox blood, with 0'6, and about the same for frog's blood.
Very slight differences of external condition will tend to alter the per-
meability of the blood corpuscles both for haemoglobin and for other
substances. A minute diminution in the alkahnity, such as is produced
by the addition of 0"003 per cent. HCl, so alters the permeabihty as to
cause proteid to pass from the corpuscles into the serum, and chlorides or
phosphates to pass into the corpuscles from the serum ; a minute increase
of alkalinity has the opposite effect. The passing of oxygen and carbonic
acid respectively through blood produces like physical changes, and it has
been suggested that these changes may come into operation in connection
with the metabolic exchanges in the capillaries.^ These osmotic effects
alter the total volume of the corpuscles as compared with the plasma ;
the proportional alterations are determined by centrifugalising blood,
and then measming the respective amounts of subsided corpuscles and
superjacent plasma.* Laky blood is j)roduced not only by water and
dilute solutions of neutral salts, but also by many other reagents or con-
ditions, such as crushing of the corpuscles, freezing and thawing the
blood, and also by the action of acids, of alkalies, of bile salts, of ether and
chloroform, of heat and electricity.^ In all cases the permeability of
the envelope of the red corpuscle (see p. 154) becomes altered either by
mechanical means or by the solution of one or more of its constituents,

^ Havincr the same osmotic pressure (de Vries, Ztschr. f. phijsikal. Chem., Leipzig, 1888,
B<1. ii. S. 415).

- Hamburger, Arch. f. Physiol., Leipzig, 1886, S. 476 ; Ztschr. f. Biol., Munclien, 1890,
Bd. xxvi. S. 414.

^ Han:burger, Ztschr. f. Biol., Mliuclien, 1892, Bd. xxviii. S. 405; Arch. f. Physiol.,
Leipzig, 1892, S. 513 ; 1893, Suppl. Heft, S. 153 ; and Verhandel. d. Tc. Akad. v. Wetensh.
te Amsterdam, 1897, S. 368.

* Koeppe, Arch. f. Physiol., Leijizig, 1895, S. 154 ; Hedin, Skandin. Arch. f. Physiol.,
Leipzig, 1895, Bd. v. S. 207 and 238.

■' For literature of this, see Rollett in Hermann's "Handbuch der Physiologic," Bd. iv.
S. 14.



SPE CIFIC GRA VIT V. 143

and the htemoglobiii is thereby permitted to diffuse into the circumjacent
fluid.

Specific gravity. — The specific gravity of the blood varies in health
within small limits, namely, for men, 1057 to 1066 ; for women, 1054 to
1061.^ According to Lloyd Jones,^ it is lower than this in women, averaging
1051 "5 between the ages of 35 and 45, whereas in men of the same age it
averages 1058"5. It falls a little when much fluid is injected, and is raised
a little by profuse perspiration, but the changes thus produced are very
small.^ It is slightly less in children than in adults, but it is higher in
the foetus than in the mother ; and it is highest in the child at term, in
which it is 1066, the specific gravity of the maternal blood being then
only about 1050."^ The diurnal variations are normally so small as to be
almost negligeable. Passive congestion of the part from which the speci-
men examined is taken increases the specific gravity, whereas active con-
gestion lowers it. It varies also according to the part of the body from
which it is taken, such variation being probably due to accidental admix-
ture with lymph. Thus Lloyd Jones found a difference of as much as
three or four per 1000 between blood from the finger (lower) and blood
from the skin over the shin (higher). Of the animals examined, it has
been found higher in birds than mammals, and to vary somewhat in these
animals in different species. The variations in age and sex are closely
related to variations in the amount of hemoglobin. SaUne solution
(NaCl, 075 per cent.) injected in quantity into the blood only depresses
the specific gravity for a short time. The specific gravity of blood from
a vein is practically the same as that from the corresponding artery, if
care be taken to avoid venous congestion.^

The specific gravity of the blood falls after the removal of blood,
doubtless from absorption of the specifically lighter lymph from the
tissues. It subsequently (in about six hours) not only returns to
normal, but even rises above normal ; after about twelve hours it has
permanently recovered its normal specific gravity.^

Almost any operation performed upon an animal, especially one
involving exposure or irritation of a serous membrane, will produce an
increased percentage of corpuscles (polycythsemia), or a corresponding
diminution of plasma. This is due, not to increased formation of cor-
puscles, but to exudation of plasma in the inflamed or irritated part.'^

^ Hanimerschlag, Ztschr. f. klin. Med., Berlin, 1892, Bd. xx. S. 444. The results of
other workers will be found in this paper. For the older literature, see EoUett, o}). cit., S.
134. The numbers given by Peiper {CentralU. f. klin. Med., Bonn, 1891, Bd. xii. S. 217)
are 1"05.5 as the average for men, and 1 '053 for women.

^ Journ. Physiol., Cambridge and London, 1888, vol. viii. p. 1.

3 Schmaltz, Arch. f. klin. Med., Berlin, 1891, Bd. xlvii. S. 145; Grawitz, Ztschr. f.
klin. Med., Berlin, Bd. xxi. S. 459, and Bd. xxii. S. 411.

* Lloj'd Jones, op. cit.

^ Cohnheim and Zuntz, Arch. f. d. ges. Physiol., Bonn, 1888, Bd. xlii. S. 303.
For the effects of varying conditions of health and disease upon the specific gi'avity
of the blood consult Lloyd Jones, Jotorn. Physiol., Cambridge and London, 1891, vol. xii.
p. 299, where a large number of observations are accumulated. Lloyd Jones worked by
Roy's method. Scholkoft' (Diss., Bern, 1892), working by a ditferent method (pycnometer),
has obtained very similar results. Both observers agree in the important fact that the
specific gravity varies as a rule pari passto Avith the richness in haemoglobin. For the
specific gravity in different animals, and for variations exi^erimentally induced, see Sher-
rington and Copeman, Journ. Physiol., Cambridge and London, 1893, vol. xiv. p. 52.

^ Ziegelroth, Virchow's Archiv, 1895_, Bd. clxi. S. 395.

■^ See on this subject, Lbwit, "Studien z. Phys. u. Path. d. Blutes," Jena, 1892; W.
Hunter, Journ. Physiol., Cambridge and Loudon, 1890, vol. xi. S. 115; Sherrington and
Copeman, loc. cit. ; Sherrington, Proc. May. Soc. London, 1893, vol. Iv. p. 161.



144 THE BLOOD.

The methods which have been used for determining the specific gravity of
the blood are — (1) that of directly weighing a sample (pycnometer), and (2)
Eojr's method. The latter is by far the readiest, and, for small quantities of
blood, the more accurate. It consists in transferring minute drops of blood to
glycerine and water, mixed in varying proportions, and forming a graduated
series of liquids of different and known specific gravities, and in observing in
which mixture the drop tends neither to rise nor to fall. The method has been
modified by the use of benzene and chloroform mixtures instead of glycerine and
water, and also by placing the drop of blood in such a mixture, and adding benzene
or chloroform, as the case may be, until the drop remains exactly suspended,
tending neither to rise nor fall ; the specific gravity of the mixture is then
taken (Hammerschlag). It may be doubted, however, whether these modifica-
tions are more readily applied, or more accurate than Eoy's method.

Reaction. — The alkaline reaction of the blood is easily recognised, in
spite of its red colour, by appljang a drop of blood to the surface of a piece
of glazed litmus paper, and after half a minute wiping away the blood
with a piece of clean linen, wetted with distilled water or with neutral
salt solution. The part of the paper which was covered by the blood
will show a blue patch.^ A comparison may be made between different
samples of blood, by using a series of litmus papers which have been
reddened by standard acid of different strengths.^ For estimating the
amount of its alkalinity the blood is mixed in small measured quantity
with a solution of sulphate of soda, containing a definite amount of
tartaric acid,^ titrated against sodium hydroxide, and the mixture found
which is exactly neutral to glazed litmus paper. Tested by this method,"*
the alkalinity of human blood is found to be equal to about 0'200
grms. of sodium hydroxide per 100 c.c. blood.^ There appears to be
a diurnal variation, the alkalinity being lowest in the morning, and
gradually rising in the afternoon, becoming less again in the evening. It
rises during digestion.^ It is diminished by muscular work, especially
with a diet containing little or no proteid.'' On the other hand, with a
diet rich in proteids, it undergoes very little alteration. In accordance
with this, it is found that carnivora resist an artificial diminution of the
normal blood alkalinity (such as would be caused by giving dilute mineral

^ Schafer, Journ. Physiol., Cambridge and Loudon, 1881, vol. iii. p. 292.

- Haycraft and Williamson, Proc. Roy. Sac. Eclin., 1888, vol. xv. p. 396. For fallacies
in the clinical application of this method, see Hutchison, Lancet, London, 1896, vol. i.
p. 616.

^ Lassar, Arch. f. d. ges. Physiol., Bonn, 1874, Bd. ix. S. 44; Drouin (These, Paris,
1892) used oxalic acid.

■* The principle of the method is due to Zuntz, who, however, used phosphoric acid
[Centralhl. f. cl. raed. JVissensch., Berlin, 1867, S. 801) ; but the details M-ere greatly
improved by Landois ("Eeal-Encyklopadie," Aufi. 2, Bd. iii., article "Blut"). For other



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