no consequence to healthy persons may excite in the purpuric profuse
hemorrhage, free or interstitial. Violent emotions and physical efforts
should be avoided, as in stimulating the heart's action a condition of
increased blood-pressure ensues that may readily result in
extravasation.
There are no remedies that exert a specific influence over purpura, and
yet quite a number have enjoyed, and still enjoy, high reputation in
controlling the symptoms. Probably the most frequently employed remedy
against purpura is sulphuric acid, preferably the aromatic sulphuric
acid, in doses of from 15 to 20 drops, diluted well with water and
administered every third or fourth hour. It is certainly an agent of
value, though some authors maintain that it has no efficacy
(Immermann). Acetate of lead undoubtedly exercises an influence over
the course of the disease. More recently, ergot has been employed. Its
use has been highly extolled by Buckley and others. Very large doses
may be given. The hypodermic use of ergotin has been followed by
results most gratifying to those employing it. Oil of turpentine has
enjoyed considerable reputation. A remedy that undoubtedly has a good
effect is iron, both as {194} exercising a controlling action over the
bleeding and as assisting to repair the resulting anæmia. The tincture
of the chloride is the most suitable preparation, and may be given in
large doses (from minim xx to fluidrachm ss), well diluted, every
fourth hour. Care must be exercised to avoid irritating the digestive
organs with it. Formerly, venesection was employed to prevent the
occurrence of hemorrhage, but its efficacy in this direction is at
least doubtful, and cannot but help to intensify the disastrous
consequences of severe and protracted attacks.
The various complications that may arise, as well as the general
results of purpura, must be treated symptomatically. For the mucous
membranes astringent washes should be used, and in favorable situations
the tampon may sometimes be employed with profit. In purpura rheumatica
the arthritic pains will be alleviated by anodyne liniments and
plasters, and the often accompanying abdominal pains and colic by
anodynes internally administered. Hæmatemesis, hæmaturia, etc. must be
treated upon general principles. The results of profuse hemorrhage must
be combated with stimulants. Transfusion of blood has been proposed and
practised for the extreme anæmia that sometimes occurs, but without
encouraging results. If necessary, the bowels may be kept free by mild
aperients. In severe cases rest in bed should be rigidly enforced until
after the establishment of convalescence. Quinia, iron, and nux vomica
are indicated above all other remedies for the anæmia resulting from an
attack of purpura.
{195}
DIABETES MELLITUS.
BY JAMES TYSON, A.M., M.D.
Diabetes mellitus is a term applied to a group of symptoms more or less
complex, of which the most conspicuous is an increased flow of
saccharine urine--whence the symptomatic title. It is associated with a
derangement of the sugar-assimilating office of the liver, as the
result of which an abnormally large quantity of glucose is passed into
the hepatic vein and thence into the systemic blood, from which it is
secreted by the kidneys. The condition is sometimes associated with
alterations in the nervous system, at others with changes in the liver
or pancreas, while at others, still, it is impossible to discover any
structural alterations accompanying it.
[Illustration: FIG. 1. To show the position of the punctures required
to produce glycosuria, the lobes of the cerebellum are separated. Below
are seen the restiform bodies, the divergence of which circumscribes
the apex of the calamus scriptorius and the fourth ventricle. The
puncture _p'_ produces glycosuria; the puncture _p_, glycosuria with
polyuria; and a puncture a little higher up than _p_, albuminuria.]
PATHOLOGY AND PATHOGENESIS.--Notwithstanding that this disease has been
recognized for two centuries and a half, that abundant opportunity has
been furnished for its post-mortem investigation, and that experimental
physiology has contributed much information bearing upon the subject,
its pathology is still undetermined. Experiment has, however, rendered
it very likely that all cases of essential glycosuria--that is, all
cases in which saccharine urine is not the direct result of
over-ingestion of sugar or sugar-producing food--are accompanied by a
hyperæmia of the liver. This hyperæmia, with its consequent glycosuria,
can be induced by puncturing or irritating the so-called diabetic
area[1] in the medulla oblongata. This area corresponds with the
vaso-motor centre, and with the roots of the pneumogastric or vagus
nerve in the floor of the fourth ventricle; whence it was at first
inferred that this nerve is the excitor nerve of glycosuria. It was
soon ascertained, however, that when the pneumogastric was cut,
glycosuria ensued only when the central end was stimulated, while {196}
stimulation of the peripheral portion was without effect. Whence it
became evident that this nerve is not the excitor, but the sensory
nerve concerned in glycogenesis.
[Footnote 1: The diabetic area, as marked out by Eckhard, and which
corresponds with the vaso-motor area, as defined by Owsjannikow
(_Ludwig's Arbeiten_, 1871, p. 21), is bounded by a line drawn four or
five mm. above the nib of the calamus scriptorius, and another about
four mm. higher up.]
It was also learned in the course of continued experiment that
glycosuria resulted upon transverse section of the medulla oblongata,
of the spinal cord above the second dorsal vertebra, of the filaments
of the sympathetic accompanying the vertebral artery, upon destruction
or extirpation of the superior cervical ganglion, and sometimes, but
not always, after division of the sympathetic in the chest (Pavy); also
after section or careful extirpation of the last cervical ganglion,
section of the two nerve-filaments passing from the lower cervical to
the upper thoracic ganglion around the subclavian artery, forming thus
the annulus of Vieussens,[2] and after section or removal of the upper
thoracic ganglion.
[Footnote 2: Cyon and Aladoff, reprint from the _Mélanges biolgiques_
and _Bullétin de l'Académie Impériale de Petersbourg_, vol. xiii. p.
91; cited by Dr. Brunton in the Lectures named in note on p. 198; also
_British Medical Journal_, Dec. 23, 1871, p. 731.]
[Illustration: FIG. 2. The last cervical and first thoracic ganglia,
with circle of Vieussens, in the rabbit, left side. (Somewhat
diagrammatic, many of the various branches being omitted.)
_Trach._, trachea; _Ca._, carotid artery; _n. vag._, the vagus trunk;
_n. rec._, the recurrent laryngeal; _sym._, the cervical sympathetic
nerve ending in the inferior cervical ganglia, _gl. cerv. inf._ Two
roots of the ganglion are shown--_rad._, the lower of the two
accompanying the vertebral artery, _A. vert._, and being the one
generally possessing accelerator properties; _gl. thor. pr._, the first
thoracic ganglion. Its two branches, communicating with the cervical
ganglion, surround the subclavian artery, forming the annulus of
Vieussens. _sym. thor._, the thoracic sympathetic chain; _n. dep._,
depressor nerve. This is joined in its course by a branch from the
lower cervical ganglion, there being a small ganglion at their
junction, from which proceed nerves to form a plexus over the arch of
the aorta. It is this branch from the lower cervical ganglion which
possesses accelerator properties, hence the course of the accelerator
fibre is indicated in the figure by the arrows. (Modified from Foster's
_Physiology_.)]
All these operations paralyze the vaso-motor nerves by which, in
health, the blood-vessels of the liver are kept in a state of tonic
contraction; hence these vessels dilate when the nerves are cut. From
the facts named we also learn the path of the glycogenic influence,
which must be from the medulla oblongata into the spinal cord, thence
by the filaments of the {197} sympathetic which accompany the vertebral
artery into the lower cervical ganglion; thence through the annulus of
Vieussens into the first dorsal ganglion; and thence through the
prevertebral cord of the sympathetic, and branches not precisely
determined, to the hepatic blood-vessels as shown by the dotted line in
Fig. 3.
[Illustration: FIG. 3. Diagram showing the course of the vaso-motor
nerves of the liver, according to Cyon and Aladoff. These nerves are
indicated by the dotted line which accompanies them: _a_, vaso-motor
centre; _b_, trunk of the vagus; _c_, passage of the hepatic vaso-motor
nerves from the cord along the vertebral artery; _d_, fibres going on
each side of the subclavian artery and forming the annulus of
Vieussens; _e_, first dorsal ganglion; _f_, ganglionated cord of the
sympathetic; _g_, the spinal cord; _h_, the splanchnic nerves; _i_,
coeliac ganglion, from which vaso-motor nerves pass to the hepatic and
intestinal vessels; _k_, the lungs, to which fibres of the vagus are
seen distributed; _l_, the liver; _m_, the intestine; _n_, the arch of
the aorta.]
I say, by branches of the sympathetic not precisely determined, because
our power to produce artificial diabetes fails below the first thoracic
ganglion; for section of the sympathetic between the tenth and twelfth
ribs, and of the splanchnics, is not followed by glycosuria, although
the vaso-motor nerves to the liver are known to pass through them.
According to Eckhard,[3] the phenomena of artificial glycosuria are
irritative and not paralytic. This view he believes sustained by his
own experiments, according to which if the splanchnics, through which
{198} the vaso-motor nerves of the liver pass, are cut prior to the
diabetic puncture, not only does this operation fail to produce
glycosuria, but it even renders ineffectual the puncture itself as well
as the section higher up. But Cyon and Aladoff remind us that it is not
mere dilatation of the hepatic vessels, but increased velocity in the
movement of the blood, which deranges the sugar-assimilating function
and causes glucose to appear in the urine. The vaso-motor nerves of the
intestinal blood-vessels also pass through the lower part of the
sympathetic and the splanchnics, and section of the latter must cause
these blood-vessels to dilate. Now, in rabbits, in which this
experiment is usually performed, the digestive canal is very long, and
the blood-vessels so capacious that when dilated they hold as much
blood as all the rest of the vascular system together, so that when the
lower sympathetic and splanchnics are cut, so much blood goes into the
intestines that the increased velocity required in the blood-vessels of
the liver to produce glycosuria is impossible. But if the vessels of
the liver be first dilated by puncturing the floor of the fourth
ventricle, section of the sympathetic or of the splanchnics may then be
made without arresting the formation of sugar; whence it would appear
that the glycogenic influence may still pass through the lower
sympathetic and splanchnics.
[Footnote 3: _Beiträge zur Anat. und Physiologie_, iv., 1859, p. 1;
vii., 1873.]
In view of the fact that Eckhard[4] has failed to confirm the results
of Cyon and Aladoff, but has traced the glycogenic influence down the
spinal cord as far as the fourth dorsal vertebra in rabbits, and even a
little lower, and that Schiff[5] has shown that diabetes sometimes
results after section of the anterior columns of the cord between the
medulla and the fourth cervical vertebra, Dr. Brunton[6] suggests that
the vaso-motor nerves of the liver may not always leave the spinal cord
to join the sympathetic by the branches accompanying the vertebral
artery, but sometimes pass farther down the cord, leaving it by the
communicating branches to some of the dorsal ganglia, as indicated in
Fig. 4.
[Footnote 4: _Beiträge zur Anat. u. Physiologie_, viii., 1877, p. 79.]
[Footnote 5: _Untersuchungen über Zuckerbildung in der Leber_, 1859, S.
108.]
[Footnote 6: _Lectures on the Pathology and Treatment of Diabetes
Mellitus_; reprinted from the _British Medical Journal_, 1874, p. 12.]
[Illustration: FIG. 4. Diagram showing another course which the
vaso-motor nerves of the liver may take. The letters indicate the same
parts as in Fig. 3. The hepatic vaso-motor nerves are here represented
as passing lower down the cord than in Fig. 3, and leaving it by
communicating branches to the second dorsal ganglion. It is possible
that they may sometimes leave by the branches to the first, and
sometimes by those going to a lower, ganglion. In such cases any
irritation to the third or one of the other cervical ganglia may cause
diabetes by being conveyed along the vertebral artery and up the cord,
as indicated by the dark line, to the vaso-motor centre, where it may
cause reflex inhibition in the same way as any irritation to the
vagus.]
It is evident that an agency involving any part of this tract in such a
way as to paralyze the vaso-motor nerves of the liver is capable of
producing glycosuria. Such cause may operate upon the central ganglia
whence the nerves emanate, as the vicinity of the oblongata and upper
parts of the spinal cord or the coeliac ganglion and its branches,
including those to the pancreas. Or the irritation may be peripheral
and its effects reflex. We have seen that irritation of the central end
of the cut vagus will produce glycosuria. Any irritation, therefore,
involving the peripheral distribution of this nerve may produce it.
Hence embarrassed respiration, whether due to disease of the
respiratory passages, strangulation, or inhalation of irrespirable
gases and anæsthetics, produces glycosuria in dogs and rabbits; and
this symptom has been known to attend these conditions in the human
subject. So, too, glycosuria may be produced by such substances as
woorara, strychnia, morphia, and phosphoric acid, introduced into the
blood and irritating the terminal filaments of the pneumogastrics, or
it may be brought about secondarily through the embarrassed respiration
these drugs produce. Such peripheral {199} irritation may reside also
in the stomach, intestines, liver, or any organ to which the
pneumogastric is distributed.
It is not unlikely that irritation of the extremities of sensory nerves
other than the pneumogastric may become the cause of reflex glycosuria.
Even puncture of the floor of the fourth ventricle itself may be reflex
in its operation, the roots of the pneumogastric being thus irritated.
The effect of the irritation conveyed to the glycogenic centre is to
inhibit the usual tonic influence of the vaso-motor nerve upon the
vessel walls. Among the experimental irritations, in addition to
puncture of the floor of the fourth ventricle, which produce glycosuria
by reflex action, are injuries of the cerebral lobes and cerebellum,
optic thalami, cerebral peduncles, pons varolii, middle cerebellar
peduncles, and even of the sciatic nerve and brachial plexus; whence it
may be inferred that pathological irritation in the same situations may
result in a glycosuria, which is temporary or permanent according as
the irritation is temporary or permanent.
Finally, there is no reason why an inhibitory reflex action should not
originate in the sympathetic itself. When we remember that this nerve
is both sensory and motor in function, and that the inhibitory
influence to which the heart's action is subject is accomplished
through the sympathetic as a sensory nerve and the pneumogastric as a
motor, there is no reason why similar results may not be brought about
by the sympathetic alone. This being the case, we need not ascribe
glycogenic phenomena to irritation in Eckhard's sense--that is, to a
direct stimulant action of the irritant upon the vaso-motor nerves of
the liver--but may suppose a sensory influence to ascend one set of
sympathetic filaments and an inhibitory influence to descend through
another.
Dr. Pavy has recently put forward some chemical theories which explain
the action of the hyperæmia in producing glycosuria, but they do not
account for the hyperæmia itself. In healthy digestion the
carbohydrates (starch and sugar) are converted, not into glucose, but
into maltose, C_{12}H_{22}O_{11}, dextrin being intermediate in
composition. Maltose is absorbed and assimilated, converted into
glycogen. So, too, when glucose is ingested as such, it is converted by
the glucose ferment into maltose in the stomach and intestines. For the
proper production of maltose and its assimilation a good venous blood,
producing a maltose-forming ferment, is necessary. In diabetes, in
consequence of the dilatation of the arteries of the chylopoëtic
viscera, the blood enters the liver too little deoxygenated, and a
glucose-forming ferment is produced. The glucose thus formed is not
assimilable, but passes off into the circulation and the urine.
MORBID ANATOMY.--Such are some of the facts bearing upon the pathology
of diabetes mellitus. Throwing out the milder type of cases, in which
glycosuria is the result of an over-ingestion of saccharine and
sugar-producing food--and these can scarcely be called instances of
essential diabetes--it is evident that glycosuria may be produced in a
variety of ways operating through the nervous system; and accordingly
we may infer that there is scarcely an organ in close relation with the
sympathetic system derangement of which is not capable of producing it.
Among these we would naturally expect to find conspicuous alterations
in the nervous centres, and yet I have never found changes in these
centres after death. At the same time, others have noted meningitis,
tubercular {200} and traumatic, apoplectic effusions, and tumors of the
brain, especially in the neighborhood of the medulla oblongata. The
alterations in the nerve-centres described by Dickinson as the
essential morbid anatomy of diabetes I have looked for in vain. These
changes are described as a cribriform or porous condition of the white
nervous matter, said to be visible to the naked eye. The spaces thus
produced are partially occupied by dilated blood-vessels, which, in
turn, are surrounded by dilated perivascular sheaths and broken-down
nervous matter, into which extravasations of blood have taken place, as
evidenced by the presence of pigment-granules. The changes are found in
the white matter of the convolutions of the brain, but fewer and larger
in the central portions. The corpora striata, optic thalami, pons,
medulla, and cerebellum are favorite seats for the largest and most
striking holes. In rapidly-fatal cases the cavities are sometimes
filled with a translucent, gelatinous substance, containing, besides
vascular elements, the globular products of nervous disintegration. In
the more chronic forms of the disease, as it occurs in elderly persons,
the excavations are usually empty, although the elements of nervous
decay are still to be found fringing the margins or collected as an
irregular sheath upon the dilated or shrunken artery. There are changes
in the cord similar to those in the brain, but less decided. But the
most striking alteration in the cord, according to Dickinson, although
not always present, is dilatation of the central canal, which in the
dorsal and lumbar regions is sometimes expanded to many times its
normal diameter, and forms a conspicuous object immediately after the
cord is divided.
These alterations have eluded the vigilance of other pathologists who
have sought for them in well-determined cases of diabetes mellitus,
while they have been found, on the other hand, in the nervous centres
when no diabetes was present. In the recent discussion on diabetes at
the Pathological Society of London, Douglas Powell[7] seemed to be the
only one who was convinced that most of Dickinson's specimens were
examples of positive lesions.
[Footnote 7: _London Lancet_, May 5, 1883, p. 776.]
A hyaloid thickening of the blood-vessels of the brain has been noted
by Stephen Mackenzie[8] and Seymour Taylor[9] in some cases, and
miliary aneurisms of the retina in one.
[Footnote 8: Discussion on Diabetes, Path. Soc. of London, _London
Lancet_, April 7, 1883, p. 593.]
[Footnote 9: Ibid., _Lancet_, May 5, 1883, p. 774.]
Of other organs, one of the most frequently found diseased is the
pancreas, and, according to Senator, it is fair to assume that disease
of the pancreas is present in about one-half of all cases of diabetes.
As the result of increased experience, I am inclined to attach much
more importance to pancreatic disease as a cause of diabetes than I did
a few years ago. Among the changes found is a pseudo-hypertrophy, which
consists chiefly in a hyperplasia of the connective tissue, fatty
degeneration of the gland-cells, and atrophy of the glandular
structure; cancerous disease; calculous concretions in the ducts with
or without obstruction; and cystic dilatation.
Facts bearing upon the relation of pancreatic disease to diabetes have
been accumulating since Cowley first discovered calculi in the pancreas
of a diabetic, and Bright pancreatic cancer in a similar case. Since
then {201} instances have multiplied to such extent that it would be
unprofitable to enumerate them. But in 1877, Lancereaux[10]
communicated to the French Academy of Medicine specimens of profound
lesion of the pancreas from cases dying of diabetes mellitus. This, he
alleged, constitutes a special and distinctive variety of diabetes,
characterized by sudden onset, emaciation, polydipsia, polyphagia, and
peculiar alvine dejections. More recently, Depierre[11] has confirmed
these observations, apparently establishing this variety of diabetes
mellitus, of which a very rapid course--six months to three years--and
the habitual presence of diarrhoea are characteristic; while the
presence of greasy or creamy stools, and the appearance in them of
undigested nitrogenous substances, may aid in the diagnosis. Precisely
such a case, running the same rapid course--less than one year--with
emaciation, uncontrollable diarrhoea, creamy stools, jaundice, and
pancreatic disease, came under the writer's care in 1882. At the
autopsy the pancreas was found enlarged, and numerous gritty particles
were disseminated through it.
[Footnote 10: "Notes et réflexions à propos de deux cas de diabète
sucre avec altération du pancréas," _Bull. Acad. de Méd._, Paris, 1877,
2d Serie, vi. 1215-1240.]
[Footnote 11: _Med. News and Abstract_, vol. xxxix., June, 1881, p.
344, from _Jour. de Méd. et de Chir. pratiques_, Dec, 1880.]
Supposing such pancreatic disease to be primary, it is evident that it
must operate through the coeliac plexus, which, with its ganglion, is
gradually encroached upon. On the other hand, it is also possible that
the disease of the coeliac plexus may be primary, and the coexisting
pancreatic disease and diabetes mellitus both secondarily dependent
upon it. This can only be settled by more careful study of the coeliac
plexus after death from diabetes, but up to the present time facts
would seem to support the view of primary pancreatic disease.