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

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salts, and drugs with marked physiological action, have been used. In
such experiments the chief points to be observed are — {a) Integrity
of the epidermis before the experiment, and absence of destructive
chemical action by the substance used during its course ; (&) absolute
exclusion of possibility of absorption by the lungs in the case of a
volatile, substance, or of a salt yielding a volatile substance under the
action of the sweat ; (c) the choice of substances capable of recognition
with certainty in minute quantities in the secretions.

Braune,- using foot baths of solutions of potassium iodide, iodine,
and hydriodic acid, with a layer of oil over the surface of the solution,
was unable to detect iodine in the secretions. Parisot,^ using baths of
watery solutions of potassium iodide and ferrocyanide, belladonna, digi-
talis, and the colouring matter of rhubarb, repeated twice a day for
three to eight days, obtained no evidence of absorption. Hiifner ^ found
no lithium l^y the spectroscope in the urine after foot baths of lithium
chloride. V. Wittich^ and Fleischer^ were unable to confirm Eohrig's'
statement, that aqueous solutions of potassium iodide are absorbed.
Winternitz^ could get no evidence of absorption of 10 to 15 per cent,
solutions of lithium chloride in water, and results with cocaine were

Again, Fubini and Pierini^'' could get no evidence of absorption of
the following solutions : — Potassium ferrocyanide, 3 per cent. ; santo-
nate of soda, 2 per cent. : salicylate of soda, 5 per cent. ; potassium iodide,
5 per cent. ; and lithium benzoate, 2 per cent., all dissolved in water.

Hence it is probably correct to conclude that watery solutions not
acting chemically upon the epidermis, and water itself, are not capable of
absorption by the intact skin of man.

If we now turn to the case of fluids that can wet the skin, such as
chloroform, ether, alcohol, etc., we find that a certain amount of
evidence of absorption is obtainable in the case of man.

Since chloroform, though an excellent fat solvent, causes pain and
blistering when long in contact with the skin of man, the experiments
have been mostly made with ether and alcohol. Ether is a better
solvent of fats than alcohol, and hence is more likely to give positive
results. Krause ^^ maintained that both alcoholic and ethereal solutions
of salts are absorbed by the skin, but Fleischer,^'^ using a volumetric

1 Quincke, Arch. f. d. ges. Physiol., Bonu, 1870, Bd. iii. S. 332.

" Diss., Leipzig, 1856.

^ Compt. rend. Soc. de bioL, Paris, 1863, tome Ivii. p. 327.

•* Ztschr. f. j)Mjsiol. Chem., Strasslnirg, 1880, Bd. iv. S. 378.

5 Hermann's "Handbuch," Leipzig, 1881, Bd. v. Th. 2, S. 257.

® Loc. cit. "^ " Die Physiologie der Haut," Berlin, 1876.

^ Arch. f. ex2ier. Path. u. PharmakoL, Leipzig, 1891, Bd. xxviii. S. 405.

^ See also Soulier, "Trait(i de therapeutique et de pliarmacologie," 1891, tome i. p. 385.
^^ Arch. ital. de bioL, Turin, 1893, vol. xix. p. 357.
" Wagner's " Handworterbuch," 1844, Bd. ii. S. 174. ^" Loc. cit.


method, could observe no absorption of absolute alcohol Ijy his own skin
in an hour and a half, and Bitter ^ denies entirely the absorption of
alcohol or alcoholic solutions of salts by the human skin. Winternitz ^
got spectroscopic evidence of lithium in the urine after keeping the
skin of the arm in contact with an ethereal solution (with a little added
alcohol) for three and a half hours, but missed the elfect with a purely
alcoholic solution. The last-mentioned observer also denies the state-
ment of Parisot,^ that solutions of atropine in alcohol and chloroform,
applied to the forehead, cause mydriasis.

It would appear that previous removal of the grease of the skin
by ether allows a slight absorption of watery solutions to take place,
for Winternitz ■* got traces of lithium in the urine on applying a watery
solution of the chloride to the skin cleaned with ether, but not till nine
hours after the application.

If a substance applied to the skin is volatile at the temperature
of the body, the vapour may possibly pass into the capillary spaces
between the epidermic cells, and dissolve in the fluid in the sweat
ducts, and so finally reach the blood vessels, and be absorbed ; but in
experiments with such substances the greatest precautions must be
taken to exclude absorption by the respiratory tract, and again wdth
human skin the results of different observers are conflicting. Eohrig's ^
positive results with tincture of iodine are denied by Fleischer,^ who,
wearing a mask with a tube to the outer air, found no iodine in the
urine up till six hours after an application to the skin of the back for
one and a half hours. Next morning Fleischer found iodine in the
urine, but this may have been absorbed by the lungs during sleep,
or the result of the destructive action of the substance on the
epidermis. Mesnil,'^ placing the arm in a Mosso's plethysmograph, filled
with vapour of iodine, could get no evidence of absorption after thirty-
two hours' exposure. On the other hand, guaiacol is asserted by several
observers to be absorbed.^

Oily solutions and unguents, since they " wet " the skin, one would
expect to be capable of absorption, but such substances are viscous and
must be mechanically forced into the intercellular spaces and hair
follicles, if any marked effect is to be obtained. According to Winter-
nitz,^ the mere application of oily solutions of veratrine and aconitine to
the skin of man is without effect. Baschkis and Obermayer ^^ obtained
evidence of presence of lithium in the urine three hours after rubbing
in an ointment of lithium carbonate, oleic acid, and lanoline, but
Fleischer ^^ could not obtain evidence of absorption of unguents holding
potassium iodide, veratrine, morphia, quinine, and salicylate of soda, nor
could Fubini and Pierini ^^ find salicylic acid in urine after painting a
solution in oil of almonds on the hand and forearm.

But the most important case is that of mercurial ointment, which is
undoubtedly absorbed into the system. In this, in addition to fine

1 Diss., Erlangen, 1883. " Loc. cit.

^ Oompt. rend. Acad. d. sc, Paris, 1863, tome Ivii. p. 327. '^ Loc. cit.

^ Loc. cit. ^ Loc. cit.

"^ Ccntralhl. f. Physiol., Leipzig u. Wien, 1894, Bd. vii. S. 775, ref.

^ Sciolla, " Cronaca della elinica medica di Genova, " 1892-93, p. 191 ; Linossier and
Lannois, Compt. rend. Soc. de. hiol., Paris, 1894, pp. 108-110 and pp. 214-215 ; Giiinard
andStourbe, ibid., 1894, pp. 180-182.

^ Loc. cit. ^^ Centralhl. f. Min. Med., Bonn, Bd. xii. S. 65.

^^ Loc. cit. ^^ Loc. cit.


globules of mercury, there is present the black oxide of the metal/
and it is probable that, after formation of calomel by the sodic chloride
of the sweat, in the presence of oxygen a further conversion into
corrosive sublimate takes place, which is finally taken up by the blood.

Though evidence of vaporisation of mercury in mercurial ointment ,
at the body temperature, can be got by hanging a gold leaf over the
preparation, such vapour cannot of course pass through wet capillary
walls into the blood. The theory also of a passage of the fine globules
of mercury through into the blood is denied by Barensprung,^ Hoffmann,^
and Eindfleisch,* though the fine particles are certainly mechanically
forced into the hair follicles, sweat ducts,^ and the interstices of the
superficial epidermic cells, thence to gradually undergo removal.

Finally, mention may be made of the fact that by taking advantage
of the cataphoric action of the galvanic current (so-called electro-
osmose),^ it is possible to force watery solutions into the capillary spaces
between the epidermic cells, and so artificially cause absorption, either
by subsequent diffusion into the blood vessels, or by the recoil of
distended spaces forcing fluid into lymphatic channels.'^ The direction
in which the fluid is moved is that of the electrical current, and the
quantity carried through a porous partition is directly proportional to
the intensity of the current, but organic membranes are far less
permeable than porous earthenware.^

It is not then to be expected that the effects with hmnan skin
w^ill be very marked, since, in practice, only a few milliamperes can be
passed with comfort to the patient.

Munk ^ got evidence of iodine and quinine in the urine, with
positive electrodes of modeller's clay moistened with potassium iodide,
and quinine in aqueous solution. Herzog ^° anaesthetised the skin with
cocaine solution on the positive electrode, when mere application without
passage of current was without effect, as also was passage of current
without cocaine.

Kahn ^^ corroborates this, getting complete angesthesia of the skin in
twenty-five minutes, by a current of 4'5 milliamperes, with return of
sensation in thirty minutes after cessation of current. With a current
of 1 milliampere, the return of sensation was complete in ten minutes.
An excised piece of skin which had been anaesthetised by passing 3 '2 5
milliamperes for thirty minutes through an anode filled with cocaine
solution tinged with a blue dye stuff, on microscopic examination showed
the dye stuff only to the depth of the rete Malpiglhi.

Lower raammals. — The results of observations upon absorption by
the skin of lower mammals are here considered apart from those obtained
from experiments on man, in order to obviate any tendency to treat the

1 Barensprung, Journ. f . i^rakt. Glum., Leipzig, 1850, S. 50 ; Voit, Ann. d. CTewi., Leipzig,
1857, Bd. civ. S. 3 ; Hermann, " Lehrbucli d. exper. Toxicologic," Berlin, 1874, S. 212.

2 Loc. cit. ^ Diss. Wlirzbnrg, 1854.
■1 Arch./. Dermat. u. Syph., Wien, Bd. iii. S. 309.

■' Neumann, JFim. med. Wchnsdir., 1872.

® Porret, Aim. d. Phys. u. Chem., Leipzig, Bd. Ixvi. S. 272 ; du Bois-Reymond, Monalsh.
Alcad. d. JVisseiisch. , Berlin, 1860, S. 846 ; Wiedemann, Ann. d. Phys. u. Chem., Leipzig,
1852, S. 321 ; and " Elektricitat, " Braunschweig, 1883, Bd. ii. S. 166.

■^ Pascheles, Arch. f. exper. Path. u. Pharmakol., Leipzig, 1895, Bd. xxxvi. S. 100.
^ Engelmann, Arch. ne4r. d. sc. exacles {etc.), 1874, Bd. ix. S. 332.
9 Reicliert, Arch. f. Physiol, Leipzig, 1873, S. 505.
"^^ Munchen. med. Wchnschr., Bd. xxxiii. S. 222.
" Inaug. Diss., Strassburg, 1891.


cases as analogous. The skin of the mammals usually employed for such
experiments is thinner than that of man, less horny, more vascular on
account of the hair, and in some cases (rabbit) possessed of hair follicles
with wide mouths. The presence of hair is a source of trouble in experi-
ment, for, if not shaved, excoriations may be passed over, while, on the
other hand, the process of shaving is apt to be accompanied by slight
injuries to the surface.

As with man, so here there is little positive evidence of absorption of
watery solutions, and one is inclined to attribute the results of those
observers who maintain that watery solutions are absorbed, to injuries
produced in shaving, or clipping, or accidental introduction by mouth or

Forlanini ^ maintained that rabbits could be poisoned by painting
aqueous solutions of strychnia, acidulated with acetic acid, on the skin,
but V. Wittich ^ could not get the effect on white rats, nor Fubini and
Pierini ^ with guinea-pigs, while Winternitz * obtained both positive and
negative results with live rabbits. Fubini and Pierini allowed the tails
of rats to soak in strychnia and potassium cyanide solutions (for forty
minutes in the former case and two hours in the latter) without effect.
Traube-Mengarini 5 painted the skin of dogs daily for two months
with aqueous solution of potassium ferrocyanide, killed the animals, and
treated skin sections with ferric chloride. The blue was only found
between the surface cells, not reaching deeper than the stratum granu-
losum. Acidified borax-carmine solution, applied daily for seventy days,
gave a like result. Fleischer ^ got iodine through the belly skin of a
rabbit (into a watch-glass of water introduced under the skin) in two
hours from a cylinder full of the tincture, but admits that the structure
of the skin was altered.

With ether and chloroform solutions, absorption is more marked
in the thin skin of the rabbit, guinea-pig, and rat, than in that of man.

Waller '^ immersed the leg of a guinea-pig in a mixture of chloroform
and tincture of aconite, and was able to poison the animal, an effect not
produced by the tincture alone. White rats with the foot in a chloro-
form solution of atropine, exhibited a dilated pupil in two or three
minutes ; with the tail (thicker skin) immersed, not till half an hour
had elapsed. Strychnia in the same way he found was absorbed from
solutions in chloroform, but not from those in alcohol.

Winternitz^ also found that rabbits absorb strychnia solution in
chloroform, and points out that this is not merely an effect of " stimu-
lation," because a previous treatment of the skin with mustard or
ammonia does not hasten the intoxication.

Winternitz has also pointed out that cleansing the skin of rabbits
with ether or chloroform allows absorption of aqueous strychnia solution
to take place, and, microscopically, it is found that silver nitrate solution
penetrates more deeply if the skin is so treated. Alcoholic washing of
the skin also tends to make subsequent absorption of aqueous solution
possible, but to a far slighter degree than in the case of chloroform and

^ A%n. univ. di med. e cMr., Milano, 1868, vol. ccv. p. 473.

^ Loc. cit. ^ Loc. cit. * Loc. cit.

^ Arch. f. Physiol., Leipzig, 1892, Supp., S. 1; Arch. ital. de UoL, Turin, 1891,
vol. xvi. p. 159.

^ Loc. cit. 7 Proc. Roy. Soc. London, 1860, vol. x. p. 122. ^ Loc. cit.

VOL. I. — 44


Experiments upon the absorption of oils and unguents by the
skin of animals seem to have given conflicting results in the hands
of different observers. Lassar^ anointed rabbits with oil for days in
succession, and maintains that the organs became loaded with oil. V.
Sobieranski^ asserts the same for vaseline rubbed into the skin of dogs
and rabbits, and states that the substance is found especially in the
muscles. Fleischer ^ denies the effect, as also does Winternitz,' though
the latter observer was able to kill a rabbit by inunction of strychnia
(2 per cent.) in oil. Adam and Schoumaker ^ got negative results
from the inunction of an ointment of strychnia and vaseline into the
skin of the necks of dogs. Mercury, however, is absorbed by dogs and
horses from mercurial ointment. Thus Miiller ^ rubbed mercurial oint-
ment into clipped dogs and horses, and found mercury in the fseces and
urine. An ointment of corrosive sublimate, sodic chloride, and fat, gave
mercury in the faeces and urine ; lead was passed after rubbing in an
ointment of a lead salt, and application of a potassic iodide ointment
gave iodine in the sahva. Aqueous solutions of sublimate were without
effect when applied to the skin of these animals.

Cataphoric transfer of solutions through the skins of lower mammals
can be induced more easily than in the case of man. Munk ' was able to
poison rabbits with strychnia in aqueous solution, and Kahn ^ obtained
the pharmacological effects of physostigmine and strychnia on rabbits,
and of apomorphine on dogs, by passing a current of 3-5 milliamperes
through "2 per cent, solutions in the positive electrode, and in all cases
proved that applications of the solutions without concomitant passage
of current was without effect.

Frog. — In the case of the frog the conditions for absorption of
watery solutions by the skin are far more favourable than in that of
mammals, for the surface is kept constantly moist by the secretion of
the skin glands, and no greasy matter is present, so that it is a matter
of common laboratory experience that poisonous solutions applied to
the skin of the animal rapidly produce their specific effects. •

Blood vessels are abundant in the skin, especially in that of the
back, and substances must diffuse with ease through or between the
moist epidermic cells into the underlying vessels. It would, however,
appear probable that, in addition to simple diffusion, the physiological
condition of the lower epidermic cells affects the passage of substances
through the skin.

Eeid^ found that the direction of easier osmotic transfer of fluid
through freshly removed frog's skin is (provided the fluids used are
not deleterious) from without inwards, i.e. the reverse of the direction
of easier filtration through the dead skin ; but that, as its vitality
declines, the skin becomes less and less permeable from without
inwards, and finally is more permeable in the reverse direction. The
duration of the first period, during which the skin is more permeable

^ Virchow's Archie, 1879, Bd. Ixxvii. S. 157 ; " Verhaudl. d. physiol. Gesellsch.," in
Arch.f. Physiol., Leipzig, 1880, S. .563.

^Arch.f. exjyer. Path. m. PharmakoL, Leijizig, Bd. xxxi. S. 329.

^ Virchow's Archiv, Bd. Ixxix. S. 558. •* Loc. cit.

^ Journ. de pho.rtnacol. , Bruxelles, 1891.

'^ Arch. f. toissensch. u. ^irakt. Tlncrh., Berlin, Bd. xvi. S. 309; reference in
CenLralU.f. PlnjsioL, Leipzig u. Wien, 1891, lid. iv. S. 550.

■^ Loc. cit. ^ Loc. cit.

^ Journ. Physiol., Cambridge and London, 1890, vol. xi. p. 132.

FROG. 691

from without inwards, is directly associated with the vigour of the
animals, lasting seventy to eighty hours after death in strong frogs,
but only twenty-four hours or so in feel^le animals at the end of the
breeding season.

Again, the magnitude of an ordinary osmotic stream, maintained
through freshly removed skin by means of solutions, whose injurious
effect on tissue life is minimal, is capable of variation in the direction of
increase or decrease, by such conditions as are known to exalt or depress
the activity of living matter. If an osmotic current is set up in the
direction from without inwards through living frog's skin (the normal
direction of greater permeability when the skin is fresh), the presence
of a stimulant (alcohol) increases, while that of a depressant (chloro-
form) decreases the current ; on the other hand, if the osmotic current
has been set up in the reverse direction, i.e,. from within out, the stimu-
lant causes diminution, and the depressant augmentation of the amount
of fluid transferred from the inner to the outer surface of the skin in a
given period of time. The phenomena failed to manifest themselves
when dead skin was made the subject of experiment. The same observer ^
was also able to demonstrate the existence of a current of "6 per cent,
sodium chloride solution from the outer to the inner surface of freshly-
removed skin, when the same solution at equal pressure was on either
side, and hence filtration and osmosis put out of court.

These results are difficult to explain, and must provisionally be
attributed to some unknown epithelial action.

'^Brit. Med. Journ., London, 13th Feb. 1892.


By M. S. Pe-aibeey.

Contents : — Historical, p. 692 — Respiratory Clianges in Air-Methods, p. 694 —
Conditions affecting Respiratory Exchange, p. 700 — Cold-Blooded Animals, p.
701 — Fishes, p. 704 — Warm-Blooded Animals, p. 706 — Influence of External
Temperature, p. 709— Of Muscular Activity, p. 714— Of Food, p. 717— Of Size
of Animal, p. 720— Of Time of Day, p. 721— Of Age, p. 722— Respiration by
Skin in Amphibia, p. 723 — In Mammals, p. 725 — Effects of Varnishing Skin,
p. 727 — Respiration in Alimentary Canal, p. 728 — Respiration of Foetus,
p. 730 — Of Embryo, p. 733 — The Respiration of different Gases, p. 735 — The
Respiration of Vitiated Air, p. 741 — Asphyxia, p. 743 — Exchange of Gases
between Blood and Air, p. 745 — Frequency of Respiration in Man, p. 747 — In
Animals, p. 753 — Changes in Composition of Air, p. 754 — Effect of Respiration
on Blood, p. 756 — Gases of Blood- Methods, p. 757 — Arterial and Venous Blood,
p. 760 — Condition of Gases in Blood, p. 765 — Causes of Gaseous Exchange
between Blood and Air, p. 773 — Exchanges of Gases between Blood and
Tissues, J). 780 — Causes of such Exchange, p. 783.

Eespikation is essentially the intake of oxygen and the output of
carbon dioxide by living cells. In the higher animals two phases of
respiration are distinguished — the external, the exchange of gases between
the air or water and the blood ; and the internal, the exchange between
the blood, lymph, and the tissues.

Historical Account.^ — The view held by Aristotle (384-322 B.C.), and
after him even until the fifteenth century, was that respiration drew air into the
heart and arteries, and so cooled the blood. Malpighi (1621-1694) discovered
the alveoli of the lungs, and saw the blood flowing through the capillaries of
the alveoli of a frog's lung; and Fracassati,'^ in 1665, noticed that the lower
layer of a blood clot was much darker in colour than the upper, but that on
exposure to the air the lower became florid red. Hook ^ showed the following
experiment at a meeting of the Royal Society in 1667. The ribs and diaphragm
of a dog were cut away, and the trachea connected with a pair of bellows.
The dog fell into convulsions, but revived Avhen air Avas blown into the lungs.
Numerous small holes were now made in the surface of the lungs, and by means
of two bellows the lungs were kept constantly distended with fresh air ; the
dog lay still, and its heart beat regularly. A piece of lung was cut ofi^, and it
was noticed that the blood circulated even when the lungs were collapsed.
Hook therefore came to the conclusion that the cause of death was not the
stoppage of the circulation, but the want of a suflficient supply of fresh air.
Croon ^ had previously shown before the same Society a similar experiment ;

^ For further details see Bostock's "Physiology," 2nd edition, 1828, vol. ii. p. 61 ;
Paul Bert, " Lecons sur la physiol. comp. de la resiiiration," Paris, 1870, p. 1; Zuntz,
Hermann's •'Handbuoh," Bd. iv. Th. 2, S. 5.

2 Phil. Trans., London, 1667, p. 492. - Ihicl., 1667, p. 539.

■* Dcrham's " Physico-Theology," 4th edition, 1716, p. 146.


he strangled, a pullet until it showed no signs of life, and then restored it by
blowing air into its lungs.

Boyle/ in 1666, showed by numerous experiments with the air-pump that
a supply of fresh air was essential to life, both animal and vegetable, and he
was of the opinion "that the depuration of the blood was one of the ordinary
and principal uses of resi^iration."

Mayow ^ (1668-1674) was the first to discover the real function of respira-
tion ; he showed that air was a mixture, and that one of its constituents, which
he named the nitro-aerial gas, was necessary for the support of a flame, that it
combined with sulphur and other substances with the production of acids,
that during calcination metals also combined with it and thus increased in
weight. The nitro-aerial gas (oxygen) was necessary for all forms of life, and
the respiration of an embryo was analogous to that of the adult. Mayow saw
the analogy of respiration to combustion, and held that the function of respira-
tion was to absorb the nitro-aerial gas and to remove the vapours arising from
the blood.

Stephen Hales,^ about the year 1726, showed that animals in a closed
vessel absorb air, and that a similar change is effected by a burning candle.
He also observed, by experiments upon himself, that air is absorbed during
respiration, and that "noxious vapours" are produced by repeatedly breathing
air in a bladder ; these noxious substances, he found, could be removed by
potash, and the air rendered fit for breathing. Hales suggested the use of a
bladder of air and such an absorbent in the foul air of coal mines. He believed
that during respiration the air cooled the blood and removed aqueous vapour
and noxious substances, but he rejected the view of MayoAV that the blood
combined with the nitro-aerial gas.

About the year 1757, Black* discovered that a quantity of "fixed air"
(carbon dioxide) was given off from the lungs, and that the expired air chiefly
differed from the inspired by the addition of that gas. He observed that
animals placed in carbon dioxide gas died of suffocation.

In 1772, Priestley ^ published his " Observations on Different Kinds of Air,"
in which he showed that growing plants restored the property of supporting
animal life to air which had been vitiated by the respiration of animals or by

Online LibraryE. A. (Edward Albert) Sharpey-SchäferText-book of physiology; (Volume v.1) → online text (page 97 of 147)