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period of the experiment to account for more than two-thirds of the
fat which had been formed, even supposing the whole of its non-
nitrogenous moiety to have been transformed into fat. Therefore a
part at least of the fat formed must have been derived from the
carbohydrate in the food.

This experiment has since been repeated by subsequent observers on
different animals,^ and always with the same result, so that it may be taken
as conclusively proved that the carbohydrate of the food may be converted
into fat. The same fact may be shown by balance experiments, in which,
with nitrogenous equilibrium, there is carbon disappearance in the egesta,
showing that carbon is stored in the body in quantity more than to be
accounted for by the carbon of the proteid metabolised ; such laid up carbon
must be mainly stored as fat.* Nor is this formation of fat from carbohy-
drate by any means a unique phenomenon in the organic world. As we have
seen, it occurs in plants, in the seeds of which fat is deposited at the expense
of sugar or starch ; and in the process of fermentation of sugar, acids of the

1 Hermann's "Handbuch," 1882, Ed. vi. S. 251 to 260.

^ The very numerous original experiments by these observers, which were begun in
1847 in the private experimental agricultural station at Rothamstead, are described in
the following amongst other publications: — Re'p. Brit. Ass. Adv. Sc, London, 1852 and
1854; Journ. F.oy. Agric. Soc. Eng., London, 1849, 1851, 1852, 1853, 1855, and 1860;
PMl. Trans., London, 1859 ; Scient. Proc. Roy. Btiblin Boc. , 1864 ; London, Edinburgh, and
Dublin Phil. Mag., London, 1866 ; Jonrn. Anat. and Physiol., London, 1877. An excellent
historical and critical account of the part taken by the various foodstuffs in the metabolic
l^rocesses of the animal economy is given by the same authors in Journ. Roy. Agric. Soc.
Eng., London, 1895, Ser. 3, vol. vi. pp. 47-141.

^ Soxhlet, Ztschr. d. Landic. Vereins in Baycrn, 1881 ; B. Schultze (geese), Landw.
Jahrb., 1882 ; Tscherwinsky, Landw. Versuchst., Beriin, 1883, Bd. xxix. S. 317. (These
are quoted from Neumeister, "Lehrbuch," S. 368.) See also Clianiewski (geese),
Ztschr. f. Biol., Munchen, 1884, Bd. ii. ■ S. 179 ; C. Voit, Sitzungsb. d. k.-bayer. Alcad.
d. Wisscnsch. 7A(, Munchen, 1885, S. 288 ; Meissl, Strohmer, and v. Loronz (pig), Ztschr.
f. Biol., Miinchen, 1886, Bd. xxii. S. 63 ; I. Munk (dog), Virchoio's Archiv, 188G, Bd.
ci. S. 91 ; Kulmer (dog), Ztschr./. Biol, Miinchen, 1886, Bd. xxii. S. 272.

■* Meissl and Strohmer, Moncdsh. f. Chem., Wien, 1883, Bd. iv. S. 801 ; Sitzungsb. d. Tc.
Akcul. d. Wisscnsch., Wien, 1883, Bd. Ixxxviii. ; and Ztschr. f. Biol., Miinchen, 1886,
loc cit. ; Rubper, loc. cit.



ARE FATS FORMED FROM PROTEIDS OF FOOD '^ 933

fatty series are formed. And although it is not easy at first sight to
understand, from a chemical point of view, how carbohydrate molecules are
transformed into fatty molecules, we are not obliged to assume direct trans-
formation, for it may well be that the carbohydrates are broken down into
comparatively simple compounds, and that these are built up again by the
organism into fat.

The observations of Hanriot, with Eichet,^ furnish indirect evidence of the
transformation of carbohydrate into fat. These observers found that, with the
administration of carbohydrate food, there is a greatly increased output of
carbon dioxide Avithout a corresponding increase of oxygen intake. This fact
may be explained, according to Hanriot, by a transformation of carbohydrate
into fat,''^ in conformity with such an equation as the following : —

13(C,H,,0,) = C^^H^o^O, + 23(CO,) + 26(H,0)

(oleo-stearo-
palmitin)

Are fats formed from the proteids of the food ? — This is a question
which was for many years held to have been settled by the experiments
of Pettenkofer and Voit, and subsequently of Voit.^ These observers
found that if a dog is kept in a respiration chamber, and fed entirely on
lean meat, all the ingesta and egesta of the body being carefully deter-
mined and analysed, a comparison of the results shows clearly that in
many cases carbon of the proteid is retained within the body, and is
presumably in the form of fat, the amount of fat and carbohydrate in
the food being altogether too small to suppose that the carbon laid by
could have been derived from anything but the proteids of the food.
Moreover, proteid food increases the amount of fat in the milk of
suckling animals, and a bitch fed upon lean meat may produce much
more fat in her milk than can be accounted for by the fat and carbo-
hydrates of the food — produces, indeed, milk especially rich in fat, when
fed exclusively on lean meat."^

In confirmation of observations of this kind have been adduced the
statements that the milk of suckling animals and of nursing women
is richer in cream in proportion to the amount of proteid taken in the
diet ; that fat becomes formed in large amount by the larvae of blow-
flies, which are fed upon defibrinated blood, containing only very small
quantities of non-proteid organic material ; ^ that in the ripening of
cheese there is a diminishing amount of proteid, and an increasing
amount of fat ; ^ and that in the formation of adipocere from flesh, there
is found a diminished amount of proteids, and an increased amount of
fatty acids.'^ The formation of fat in the liver and tissues of a starving

^ Conipt. rend. Acad. d. sc, Paris, 1892, tome cxiv. p. 371.

^ Cf. also Gautier, ibid. , p. 374.

^ Ann. d. Chetn. u. Phar'm., 1862, Suppl. Bd. S. 52 and 361; Ztschr. f. Biol.,
Miinchen, 1869, Bd. v. ; also 1870 and 1871, Bde. vi. and vii. ; art. "Ernahrung," in
Hermann's "Handbuch," Bd. vi. S. 249.

■* Ssubotin, Firchoio's Archiv, 1886, Bd. xxxv. S. 561; and C'entrcclM. f. d. med. JViss-
ensch., Berlin, 1866, S. 337; Kemmerich, ibid., S. 467. Both Ssubotin and Kemmerich
worked with Pflliger. See also Voit, Ztschr. f. Biol., Miinchen, 1869, Bd. v. S. 137.

5 Fr. Hofmaun, Ztschr. f. Biol., Miinchen, 1872, Bd. viii. S. 159.

^ See on the changes accompanying the ripening of cheese, Sieber, Journ. f. prakt.
Chcm., Leipzig, 1880, N. F., Bd. xxi. S. 203 : Jacobsthal, Arch. f. d. gcs. Physiol., Bonn,
1893, Bd. liv. S. 484.

^ Lehmann {Sitzungsb. d. phys.-mcd. Gesellsch. zu Wilrzburg, 1885, S. 19) obtained an
increase of fatty acids to the extent of 3 '7 per cent, in meat kept in running water for some
months. E. Voit {Miinchen. vned, Wchnschr., 1888, S. 518) got an increase of 2 per cent,
when it was kept in milk of lime, thus excluding fungi.



934 METABOLISM,

animal poisoned by phosphorus ^ also affords strong presumption of the
conversion of proteid into fat. The fact that in the deposition of fat in
embryonic adipose tissue the fatty globules are preceded by albuminous
granules may also be given as evidence in the same direction.

So important did the extent of such formation of fat from proteid
appear to Voit, that he endeavoured, as already stated, to account for the
fattening qualities of carbohydrate food by supposing that it mainly
acts by sparing the oxidation of the proteicls (and fats), thus allowing a
larger amount of these to be transformed into body-fat.^ In support of
his views, he pointed out that if the proteid molecule is supposed to be
split up, and a portion be removed in combination with the nitrogen
as urea, the carbon, oxygen, and hydrogen which remain are not very
different from the proportion of these elements which would be neces-
sary for the formation of fat. It was indeed calculated by Henneberg ^
that 51'4 per cent, of proteid taken as food might, under the most
favourable circumstances, be supposed to be converted into fat. Eubner,
however, has shown that this estimate is too high. He calculates that
the utmost amount which could be converted into fat would be about
46 "9 per cent.

The view that the fat of the body is exclusively derived from the pro-
teid of the food is, however, no longer held by any physiologists, and Voit
has himself shown that it must in some circumstances be derived from
carbohydrate.* The above view cannot, indeed, be held, if we accept, as
we undoubtedly must, the conclusions to be drawn from experiments like
those of Lawes and Gilbert. These experiments do not by any means
exclude the formation of fat from proteid, but do exclude the possibility
of its being formed entirely from proteid, and not from any other article
of diet. That a certain amount of proteid is necessary to be added to the
diet of a fattening or suckling animal is a matter of everyday experi-
ence ; but it does not seem to be necessary that this proteid should be
greatly in excess of that which is necessary to make up for the proteid
lost from the tissues, or, in the case of the suckling animal, for that also
which appears as caseinogen in the milk. If, however, the amount of
proteid in the food is too much decreased, there is more call upon the
carbohydrates and fats of the food for the immediate production of
energy, and as a result there will be less of these to be transformed into fat.

1 Storch, abstr. in Deutsches Arch. f. Min. Med., Leipzig, 1867, Bd. ii. S. 264 ; Bauer,
Ztschr. /. Biol., Miiuchen, 1871, Bd. vii. S. 63 ; ibid., 1878, Bd. xiv. S. 527 ; Caseneuve,
Rev. mens, de med. ct cTizV., Paris, 1880, tome iv. pp. 265 and 444; Stolnikott", Arch. f.
Physiol., LeijDzig, 1887, Suppl. S. 1. Bauer found in a fasting dog, to which phosphorus had
been administered, as much as 42 per cent, of fat in the muscles, and 30 in the dry liver
substance, as against 16 7 in the muscles and 10 per cent, in the liver of control dogs. The
nitrogen excreted is at the same time greatly increased, this also pointing to increased meta-
bolism of proteid, while there is at the same time a diminished excretion of carbon dioxide,
and correspondingly less oxygen taken in. A similar formation of fat from protei'l in
phosphorus poisoning has been shown by Leo [Ztsclir. f. 2jhysiol. Ghem., Strassburg, 1885,
Bd. ix. S. 483) to occur in frogs. On the other hand, Lebedeff (^rc^.. /. d. ges. Physiol.,
Bonn, 1883, Bd. xxxi. S. 11) found in dogs which had previously been fed with linseed oil,
that the fat in the liver cells, which Avas formed after administration of phosphorus, had
the same characters as that which had been laid on in the adipose tissue ; thus indicating
a transference of fat to the liver rather than its formation there from proteid. Stolnikow
found in frogs, after extirpation of the "fat-body," that the liver became enlarged, and fat
accumulated in it under conditions of both carbohydrate and proteid nutriment, even with-
out the addition of jihosphorus to the diet.

- For further details of the evidence in favour of this view, see Voit, in Hermann's
"Handbuch," Bd. vi. S. 243-251.

^ Quoted by Voit, Art. in Hermann's "Handbuch," S. 250.

4 Biol. Centralbl., Erlangeu, 1886-7, Bd. vi. S. 243.



ACTION OF LIVER IN METABOLISM OF FATS. 935

That fat is formed from proteid, although not in the exchisive form in
which Yoit at one time was disposed to assert, has been ahnost universally
accepted by physiologists ; but this view has been strenuously attacked of late
by Pfliiger ^ who has criticised the conclusions drawn by Voit from his experi-
ments of feeding dogs upon meat, and has shown that in all probability the meat
employed contained sufficient fat to account for the fat laid on in the body with-
out supposing this to have been derived from proteid. In a dog kept by himself
and fed upon a large quantity of meat containing the least possible fat, no fat
whatever appeared to be laid on ; but what was originally present disappeared,
so that the dog, although muscular and capable of performing severe work,
was reduced to a condition of extreme leanness. Pfliiger is therefore disposed
to deny altogether the formation of fat in the animal body from proteid,^ and
considers that its sources are to be looked for exclusively in the fats and
carbohydrates of the food.^

Tn this it would appear probable that Pfliiger has gone as much to
the one extreme as Voit originally went to the other. It is unquestionable
that certain forms of bioplasm are capable of transforming proteid into fat
(as in the instances cited on p. 933). This is, in fact, admitted by Pfliiger, who,
however, contends that we have no right to assume that other forms of
bioplasm, such as that of the cells of the higher animals, possess the same
power. He is disposed to regard the change as due in all the cases cited to
the action of bacteria and fungi, such as would undoubtedly be present in
ripening cheese, in putrefying blood, in putrefying flesh, and the like. But it
has been shown that in flesh kept in milk of lime, and therefore under con-
ditions unfavourable to the growth of bacteria, fatty acids are still found to a
small extent, at the expense of the proteid; and the production of fatty degenera-
tion in the cells of starved animals, to which phosphorus has been adminis-
tered, is strong evidence in favour of their possessing such a power of forming
fat from proteid; these, taken in conjunction with the numeroiis other instances
which have been cited, appear to indicate that this power of forming fat
from proteid is a general property of bioplasm.

As regards the ultimate fate of fat, there seems to be no doubt that it
becomes oxidised into carbon dioxide and water, thus producing energy which
may take the form of either heat or work, and that this oxidation takes place
mainly in the muscular tissue.

Action of the liver in connection with the metabolism of fats. —
Very little is known on this question beyond the fact that, under certain
circumstances, there is a considerable accumulation of fat in the liver
cells. This has been held by Pavy * to indicate the correctness of his
view, that fat may be formed both in the liver and elsewhere by the
direct transformation of glycogen. But it has not been shown that the
glycogen and fat have any vicarious relation to one another ; indeed, the
contrary was found to be the case by Langley^ and by Noel Paton.^
Nevertheless, Paton's experiments show a marked increase in the fatty

1 Arch.f. d. gcs. Physiol., Bonn, 1892, Bd. li. S. 229 ; ihid., 1892, Bd. Hi. S. 1 and 239.

^ Kumagawa and Kaneda, Mitth. a. d. med. Fac, d. h.-jai^. Univ., Tokio, 1894, Bd. iii.
(abstr. in Ccntralbl. f. Physiol., Leippcig u. Wien, 1895, S. 721), were also nnable to obtain
evidence of fat formation in dogs fed upon food consisting almost exclusively of proteid.

'' For a reply to Ptliiger's ciiticisms, see E. Voit, Munchcn. med. Wchnschr., 1892,
S. 460, a.\-\A Ztschr. f. Biol., Munchen, 1896, Bd. xxxii. S. 139; also Cremer, ibid., 1897,
S. 811. Pflliger's answer to these is in Arch. f. d. gas. Physiol., Bonn, 1897, B. Ixviii.
S. 176. See also on this subject, I. Munk. Arch.f. d. gcs. Physiol., Bonn, 1894, Bd. Iviii.
S. 309 ; bXso Berl. klin. Wchnschr., 1889, No. 9.

* " Physiology of Carbohydrates," p. 258.

■' Proc. Boy. Soc. London, 1882, vol. xxxiv. p. 20 ; and 1885, vol. xxxix. p. 234.

'' Journ. Physiol., Cambridge and London, 1896, vol. xix. p. 167. Langley's state-
ments ai"e founded upon microscopical observations (in the frog) ; Paton's, upon chemical
evidence.



536 METABOLISM.

acids of the liver of the rabbit at a period after food when the glycogen
is diminishing, and he concludes that they may have been formed from
the glycogen.^ Langley^ has shown that in frogs there is a gradual
accumulation of fat in the liver, chiefly in the outer zones of the cells,
during the winter months, a time during which the glycogen is also
gradually increasing ; and, further, that both the liver fat and glycogen
tend to diminish on warming the animals in winter. The glycogen
becomes rapidly used up in the spring, and this is also the case with
the fat. Paton found (in pigeons) that the liver fat did not appreciably
diminish as the result of a four days' fast. Taken by itself, the presence
of fat in the hepatic cells merely indicates that these cells may act as a
temporary storehouse for fat. Whether such fat has been formed by
them from carbohydrate or proteid, or whether it is directly derived
from the fat of the food, and is in process of transformation in the
liver cells into a fat more intimately allied to the fat of the body, are
points which have not yet been determined, but the latter supposition
appears the more probable : for excess of fat in the food is certainly
largely stored in the liver cells.^ And it has been noticed by Lebedeff,*
and this observation is confirmed by Paton,^ that the fats of the liver
contain less oleic acid, and have a higher melting point, than those of
the body generally. IMoreover, as Hofmann showed,^ there is a higher
proportion of free fatty acids in the liver, pointing, according to Nasse,
to an active metabolism of fats in that organ.^ Lebedeff^ found in
geese which had been fed for six weeks upon peas, which are rich in
proteid but contain very little fat, that the liver, although containing
much lecithin, had no fat ; and that the fat of the omentum was also
only present in small amount. A large amount of proteid in the diet
of rabbits and kittens was found by Paton not to lead to any accumula-
tion of fat in the liver. ^

■* According to Paton, nearly one-half of the fatty acids of the liver are in combination
with lecithin. See also Heffter, Arch. f. expcr. Path. u. Pharmakol., Leipzig, 1891, Bd.
xxviii. S. 97 ; and Stolnikow, Arch.f. Physiol., Leipzig, 1887, Suppl. Heft.- S. 1.

- Loc. cit.

^ Paton, loc. cit, p. 202.

^ Ztschr.f. physiol. Chem., Strassburg, 1882, Bd. vi. S. 139.

^ Loc. cit., p. 179.

^ Beitr. z. Physiol. C. Ludidg z. s. 70, Gehurtst., Leipzig, S. 134.

''Biol. C'entralbL, Erlangen, 1886-7, Bd. vi. S. 235.

^ Loc. cit. '•' Loc. cit., p. 211.



THE INFLUENCE OF THE DUCTLESS GLANDS UPON
METABOLISM— INTERNAL SECRETIONS/

By E. a. Schafer.

Contents :— Introductory, p. 937— The Thyroid Gland, p. 938— The Pituitary Body,
p. 945— The Suprarenal Capsules, p. 948— The Spleen, p. 959.

Ceetain organs of the body have a special influence upon some of the
metabolic processes of the body. Thus the liver fulfils important
special functions in connection with the metabolism of carbohydrates
and proteids, and of those organic compounds which contain iron ;
the pancreas has an obscure but absolutely essential function in con-
nection with carbohydrate metabolism ; and removal of a large portion
of the kidneys has been shown by Bradford to produce a large increase
in the proteid waste of the tissues.^ It is also a matter of common
knowledge that removal of the ovaries or testicles may produce
profound modifications in the development of other organs, and in the
general nutrition of the body. In the case of the pancreas (and perhaps
in that of the kidney) it is by no means improbable that the gland
yields to the blood some material which influences the carbohydrate
(and nitrogenous) metabolism of other tissues. In the case of the
generative glands this is perhaps less probable : it is on the whole
more likely that these react upon the rest of the organism through the
nervous system. Numerous observations have of late been published,
commencing with those of Brown-Sequard, which have seemed to indicate
that extracts of or the expressed juices of these glands produce, when
injected hypodermically, beneficial effects upon the nervous and muscular
systems, but it is not clear that this property is not shared by other
organs rich in nuclein. Watery extracts or decoctions of the generative
glands have very much the same action, if injected into a vein, as have
extracts of other glands. In addition to the above instances, there are
certain organs of a glandular structure, but destitute of ducts, which
yield to the blood substances, which are in some cases at least
absolutely essential to the due nutrition of the body, so that the results
of the complete removal of these organs is inevitably fatal. These
substances are no doubt formed by a process of secretion, but since they
do not find their way to any free surface by means of a duct, but

1 The substance of this chapter was originally given in the form of an address to the
British Medical Association, and was published in the British Medical Journal for August
10, 1895. For the purposes of this book it has been carefully edited and many additions
have been made to it ; references to literature have also been appended.

2 Proc. Eoy. Soc. London, 1892. vol. li. These researches of Bradford have already
been noticed in a previous article (p. 656). See also Meyer, Arch, dc 2}hysiol. norm, et path.,
Paris, 1894, p. 179.



938 INFLUENCE OF DUCTLESS GLANDS ON METABOLISM.

presumably reach the blood by means of the lymphatics or blood vessels
of the organ, they have been termed " internal secretions." ^

The Internal Seceetion of the Thyeoid Gland.

The first internal secretion which may be considered is that of the
thyroid gland. That the thyroid is a secreting gland no one who
studies its structure and its mode of development can well doubt ;
except that it is unprovided in the adult state with a duct, it has all
the features of structure of secreting glands. It is formed of alveoli
which are lined by epithelial cells ; and although these cells have not
been observed to exhibit changes characteristic of secretory activity
so marked as those which have been noticed under like circumstances
in the cells of ordinary glands,^ we can observe the secreted material
within the vesicles of the thyroid iu the form of the substance known
as " colloid." Various attempts have been made to isolate the active
principle of the secretion ; these are referred to in a previous article.^
According to Drechsel,'^ there is probably more than one active substance,
and the secretion may subserve more than one essential function.^

The gland is extremely vascular and very richly provided with
nerves, and both blood vessels and nerves come into very close relation-
ship with the secreting epithelium. The glandular structure of the
thyroid is more obvious in young than in old animals, and as age
advances, as has been shown by Hale White ^ and others, the organ
undergoes a gradual process of degeneration, so that in advanced age its
normal glandular structure can only with difficulty be recognised.

Effects of ablation and disease. — As long ago as 1856, Schiff"^ found
that extirpation of the thyroid in dogs is invariably followed by a fatal
result. This observation, important as it now seems, fell for many
years into oblivion, and it was not until clinical observations had again
pointed to the importance of the gland that Schiff s experunents were
remembered. It has indeed long been recognised that extensive
disease of the thyroid, such as occurs in advanced forrhs of goitre,
are accompanied by a swollen appearance of the integument, giving a
misshapen aspect to the features and to the extremities, and leading to
an idiotic or semi-idiotic condition, which is known as cretinism. In
1873, Grull ^ described a series of symptoms, and especially a condition
of the integumental connective tissue, similar to that which is met
with in cretins, the name "myxoedema" being subsequently given to
it, because it was believed to be an oedematous condition charac-
terised by the presence of a large amount of mucin. That there is an
excess of mucin over that in ordinary connective tissue has been shown

^ In one sense all the tissues and organs of the hody form internal secretions, for they all
pass into the blood materials which have been formed as jiroducts of their meta-
bolism.

^ Hiirthle, Arch. f. d. ges. Physiol., Bonn, 1894, Bd. Ivi. S. 1 ; Anderson, Arch. f.
Anat. u. Enhvcklngsqesch. , Leipzig, 1894, S. 177 ; Schmidt, Arch. f. mikr. Anat., Bonn,
1896, Bd. xlvii. S. 181 ; Galeotti, ihid., Ikl. xlviii. S. 305.

•* Halliburton, " Chemistry of the Tissues and Organs," p. 88.

* Centrum, f. Physiol., Leipzig u. Wien, 1895, S. 705.

" Of. also Notkiii, Virchow's Archiv, 1896, Suppl. Bd. cxliv. S. 224 ; Hutchison,
Journ. Physiol., Cambridge and London, 1896, vol. xx. p. 474.

^Lancet, London, 1888, vol. i. p. 521.

'' "Untersuch. ii. die Zuckerbildung," Wiirzburg, 1859.

** Trans. Clin. Soc. London, October 24, 1873 (in vol. vii., 1874).



THE THYROID GLAND. 939

by the analyses of Halliburton ; ^ but not to the extent Ijelieved when
the term myxoedema was applied to this condition. Nor is the condi-
tion really one of oedema, but rather of hyperplasia of the connective
tissue, which becomes altered, assuming a more embryonic character,



Online LibraryE. A. (Edward Albert) Sharpey-SchäferText-book of physiology; (Volume v.1) → online text (page 131 of 147)