Source of glucose in food. Glycogen: Its use: Enlarged liver means
more glycogen. Glycosuric centre in medulla. Other glycosuric nerve
centres. Reflex action, action of drugs and poisons, phlorizin.
Disease of lungs or pancreas. Removal of pancreas in dogs. Removal of
thyroid. Diseased, liver, fatty, fibroid, hypertrophy, congestion.
Extreme fatty change arrests glycogenesis. In solipeds: 3 cases with
liver hypertrophy; 1 case with adenitis; 6 cases with emaciation; 2
cases with hæmoglobinuria. Symptoms: Emaciation, debility, langor,
fatigue, breathlessness, hollow flanks, unthrifty skin, ardent thirst,
polyuria, urine saccharine, of high density. Diagnosis by analysis of
urine, sweet taste, Fehling’s test, Trommer’s test, fermentation test.
Prognosis: Grave, diet being carbonaceous, when functional resulting
from curable disease is hopeful. Treatment: In poisoning cases,
antidotes and eliminants, in curable disorders treat these, in more
inveterate cholagogues, antiseptics, codeine, opium, croton chloral,
strychnia, phosphoric acid, iodoform, ergot, skim milk or buttermilk,
good hygiene, open air, shelter, carminatives, bitters, mineral acids,
treat complications.
Grape sugar (glucose, C_{6}H_{12}O_{6}) is undoubtedly formed in the
stomach and intestines by the action of saliva and pancreatic juice
on starch (C_{6}H_{10}O_{5}), and glucose and laevulose
(C_{6}H_{12}O_{6}) are also derived from the transformation of cane
sugar (C_{12}H_{12}O_{11}). These sugars are absorbed, transformed
into glycogen in the liver and passed into the circulation, where
they serve to maintain animal heat through their decomposition into
carbonic acid and water. They further assist in nutrition and
growth, and if their metamorphosis is imperfect they pass out of the
system in the urine, producing a temporary glycosuria. As shown
above glycogen is produced in the liver cells, and stored up there,
in greatest abundance during digestion of starchy and saccharine
food, but it is also formed in animals kept on a purely albuminous
diet, (flesh), and in the fœtal calf and unhatched chick to which
neither starch nor sugar has been furnished as food. It is produced
during the decomposition of albuminoids, along with the other end
products, leucin, tyrosin and urea. None of these last three is
found in the portal vein nor bile ducts, but all four are found in
the liver cells, and in the hepatic veins.
In health a physiological balance is maintained by the oxidation of the
glucose, mainly in the lungs, so that in the blood of the pulmonary
veins no sugar is found. There is an exception to this observable after
a full meal, rich in starch and sugar, which produces such an excess of
glycogen that a portion is carried to the kidneys and expelled by them
causing temporary glycosuria.
A small amount of glycogen is also produced habitually by the white
blood cells and stored up in them, but this is insufficient to determine
its appreciable elimination by the kidneys.
In cases of persistent glycosuria the fault may be held to consist in
one of three functional derangements:
1st. The failure of the liver to transform the alimentary sugar into
glycogen.
or 2d. The excessive production of glycogen in the liver.
or 3d. The arrest of the destructive oxidation of sugar in the lungs and
tissues.
In a diabetic patient who died suddenly of apoplexy Bernard found that
the liver was enlarged, comparing with the average as 25:14 while the
contained sugar bore the ratio of 37.5:22. This enlargement coming from
malaria or other poison, such as alcohol, ether (Harley), arsenic,
quinia (Aitken), ammonia, chloroform, or phosphoric acid (Murchison), is
an established condition of glycosuria. A rich and abundant food
(starchy and saccharine especially), or an unusually active hepatic
circulation acts in the same way.
Bernard as early as 1849 showed that the glycogenic function of the
liver was greatly increased and glycosuria determined by pricking the
floor of the fourth ventricle in the median line just in front of the
calamus scriptorius and near the root of the vagus nerve, or a few
millimeters in front of this.
It follows that irritation of this part of the medulla however produced,
whether from local disease, or by reflex action from some distant organ
in a state of irritation, may serve as the starting point of diabetes in
particular instances. That the cause may be a reflex stimulus is shown
by the suspension of the glycogenic function after section of the vagus
nerves, and its reappearance when the central end of the cut vagus is
galvanized, or, the floor of the fourth ventricle is irritated, the
direct or efferent excitation being transmitted through the sympathetic
nerve (Bernard). I can cite a case of glycosuria in a man supervening on
a severe blow on the head from a falling ledger. Brain injuries which
suspend animal functions, but not the nutritive ones, such as apoplexy,
concussion of the brain or curare poisoning are liable to induce
diabetes.
Traumatic injuries to other parts of the nervous system induce
glycosuria. Thus traumatism of the optic thalami; of the cerebral lobes
or peduncles; of the pons; of the cerebellum or of its middle or
posterior peduncles; transverse section of the medulla or of the spinal
cord opposite the second dorsal vertebra; traumatism of the superior or
inferior cervical ganglion or the first thoracic (Eckhard); of the
sympathetic twig which accompanies the vertebral artery (Pavy); of the
brachial plexus; of the solar plexus (Munck, Klebs); or of the sciatic
nerve (Schiff).
The explanation of these facts may be sought in a reflex action
established by the conveyances of irritation to the true glycogenic
centres in the brain and the transference of the efferent nervous
impulse through the sympathetic nerve to the liver. It will be borne in
mind that in the case of section of the vagus nerve electric stimulation
of its detached peripheral part has no glycogenic effect on the liver,
while galvanizing the central portion determines glycosuria.
In the case of glycosuria through stimulation of the sympathetic nerve
or its ganglia the action may be concluded to be direct. Strangely
enough, irritation of the sympathetic between the tenth and twelfth ribs
or the splanchnic nerves fails to produce glycosuria, though the hepatic
branches of the sympathetic pass through them.
In ordinary cases of reflex glycosuria it may be assumed that the
existence of irritation at the peripheral ends of the vagus and of some
other nerves, leads to an apparent glycogenic influence passing through
these to the brain, and of the distribution of the efferent impulse
through the upper portion of the spinal cord, as far as the fourth
dorsal vertebra in the rabbit (Cyon, Aladoff, Schiff), and through the
sympathetic nerve to the liver. This may account for the appearance of
the disorder as a sequel of disease in any part to which the vagus in
particular is distributed, and notably in the lungs. A number of poisons
(malarial, alcoholic, ether, carbon monoxide, amyl nitrate, curare, or
the nitro-propionic acid, methyl delphinin, morphia, chloral hydrate,
arsenic, quinia, ammonia, chloroform, phosphoric acid, and phlorizin)
produce glycosuria.
The intravenous injection of dilute saline solutions, or frequent blood
letting materially increases the sugar, probably by causing solution of
the red globules. Phlorizin is the most potent of all these agents.
Whether given hypodermically or by the stomach it causes in three hours
a marked production of glucose which continues to be eliminated for a
period of thirty-six hours. The urine may become charged with glucose to
the extent of from 6 to 13 per cent., and without any rise in the body
temperature. This artificial glycosuria may be kept up indefinitely by
the continued administration of phlorizin, and even in the fasting
animal, or one on an exclusively albuminous diet, as well as in those on
an aliment rich in saccharine or hydro-carbonaceous matter. In the frog
it produces diabetes even after the extirpation of the liver showing
that it stimulates other sources of sugar production beside the hepatic
or that it inhibits the transformation of sugar derived from the
alimentary canal and other sources.
Another suggestive source of mellituria is disease of the lungs, or any
condition which interferes with the due æration of the blood and
oxidation of the alimentary or hepatic sugar. But it cannot be assumed
that the rôle is altogether or mainly chemical. The thoracic organs
being supplied by branches of the vagus and sympathetic nerves there is
the obvious suggestion of a reflex action through the diabetic centers
in the brain. The frequent complication of diabetes with lung diseases
(inflammatory, tubercular, syphilitic, and otherwise) is abundantly
proved, whether it is to be explained on the above hypothesis or through
other unknown changes in the blood.
Diabetes has been repeatedly found in connection with disease of the
pancreas, and the complete extirpation of the pancreas in dogs gives
rise to glycosuria (Mering and Minkowski, Thiroloix, Lancereaux,
Lepine). If a small portion of the pancreas remains glycosuria does not
supervene. It has been suggested that the pancreas has a double
function, and beside its secretion, produces a glycolytic ferment which
passing into the portal blood determines the formation of glycogen in
the liver. Arrest of the pancreatic secretions does not cause
glycosuria, so it has been suggested that the glycogenic enzyme is a
product of the connective tissue cells of the pancreas. Functional as
well as structural disease of the pancreas can be conceived of as
inhibiting the production of this ferment and the consequent elaboration
of glycogen. Chauveau and Kauffmann deduce from their observations that
the action is a reflex one established through the glycogenic centres in
the medulla. Pancreatic glycosuria is especially fatal (Harley).
Finally extirpation of the thyroid body in dogs has been followed by
glycosuria (Falkenberg). This suggests a systematic examination of the
urine in all cases of goitre, with extensive glandular changes.
Apart from experimental cases diabetes in the lower animals has been
observed to be nearly always associated with diseased liver. Fatty
degeneration has been the most frequent lesion, but cirrhosis,
hypertrophy and congestion were present in other cases. In a number of
cases as the fatty degeneration reached an extreme degree, the sugar
disappeared from the urine, the hepatic cells being no longer
functionally active, and death speedily followed. The same has been
observed in the fatty degeneration attendant on poisoning by arsenic or
phosphorus.