Chapter XXV: Section XV: The Relation of Diet to Disease (2)

The carbohydrates are derived from the glucose and glycogen of the meat and from the protein molecule. They are absolutely less than in the diet of herbivores but become a factor in the disorders of this group because of the lack of exercise and the regularity of feeding. In digestion the carbohydrate becomes available for absorption and bacterial growth in the upper small intestine and appears on the other side of the intestinal wall as blood glucose in which form it is burned for energy or stored as glycogen for the future maintenance of the blood glucose.

The blood of different animals has a glucose concentration between 0.05–0.1 which for each species is quite constant, as it is regulated by the coadaptation of four factors: combustion, fermentation of glycogen, formation of fat, and elimination from the kidney. In excessive feeding the amount needed for energy is burned, the remainder is stored in the liver up to its capacity, then in the muscles and other cells, after which fat is formed and all further excess is eliminated by the kidney. Overfeeding causes an immediate overloading of the oxidative mechanism with symptoms of gastric disorder, achylia, and at times acid fermentation with irritation of the stomach walls and the development of bacteria in the organ. This is frequently followed by glycosuria, several types of which are described: (1) associated with an increased concentration of glucose following excessive ingestion exceeding the normal glycogenic function of the liver, a form common among the Herbivora, (2) that due to a reduction of the glycogenic function of the liver, (3) that associated with disease of the ductless glands in which the resulting glycosuria probably depends upon the influence of these glands upon the pancreas, (4) that dependent upon the defect of glycolysis or to an overstocked liver seen in gout, obesity or hypertrophic cirrhosis, and (5) renal glycosuria due to a lowering of the renal threshold and usually associated with gout, arteriosclerosis or chronic nephritis; this last is best explained on the ground of increased renal permeability. Normally when the blood sugar concentration rises above a certain level the elimination _via_ the kidney begins and continues until the blood has again reached its normal concentration. The relation of the kidney to glucose concentration is not constant and variation is always toward the side of lesser elimination while the kidneys become accustomed to the higher level.

Diabetes, a disease of the islands of Langerhans in the pancreas, is essentially a disturbance of sugar metabolism always associated with an exaggerated and defective fat and protein combustion. It is not only that the diabetic has lost the faculty of combustion but these abnormalities all establish states of intoxication to which the diabetic must sooner or later succumb. Among lower animals the disease is rare. Dogs are most frequently affected (about 1 in 12,000 deaths). It has also been described in horses, cattle and monkeys. In our records there was one case an Arctic fox (_Canis lagopus_) presenting a typical picture. Degeneration of the islands of Langerhans was seen in three other animals, but there was no other evidence of diabetes. This disease is not due to diet but to the absence of a normal ferment (pancreaticozymo-excitor) for one particular type of food.

IRREGULARITIES OF FAT METABOLISM.

Disorders of fat metabolism are very rare among lower animals notwithstanding the fact that fat even in the carnivorous diet, represents about 13 per cent. of the whole intake. It plays two important rôles in the body, storage for energy reserve, and as a most essential structure in cellular protoplasm, in which position it joins with protein in complex combinations of still unknown composition which present to a striking degree the phenomenon of absorption. Very marked biological differences exist in the value of fats from different sources, due to the presence or absence of vitamines. The body fat is derived from the fat of the diet or is synthesized from glucose. The former is specific to the fat consumed while the latter is specific to the animal. In omnivores the type depends upon the varying extent to which animal fats enter the diet, in carnivores it depends almost entirely on the fat intake, while in the herbivores practically all the fat is synthesized from the carbohydrate. On digestion, fat splits, yielding a glycerol and fatty acid which are collected in the lymph spaces of the intestinal mucosa, there changing to some complex combination which is not only soluble but diffusible.

Fatty infiltration and fatty degeneration are conditions of much pathological interest and of great frequency in captive animals. The researches of Mansfield[87] have thrown considerable light upon these conditions. He found that the total fat content in cases of most marked degeneration was normal or reduced. The proportion of fat free from protein was increased and the firmly bound fat decreased. This increase is due to neutral fat brought from without the organ by the blood when for any cause the oxidative powers are decreased, and setting free of the previously invisible intercellular fat and lipoids, which are normally present in the cells, by autolytic or physicochemical changes. This condition is pretty evenly distributed among the dietary groups, the liver being most commonly involved. The hepatic cells are easily degenerated by the toxins or other harmful substances passing through the organ and become passive and unable to throw off or to utilize the deposited fat. In all probability the same general situation occurs in the atheromatous changes in arteriosclerosis which on this diet shows a high incidence. The causative agent is probably some poisonous substance, possibly a protein degradation product, indol, pressor substance, acting on the intima over long periods, or at irregular but often repeated periods causing first destruction then fat accumulation. It is also possible that it may be caused by repeated absorption of some sensitizing protein. Arteriosclerosis in these animals is often closely associated with nephritis.

Obesity may result from excessive ingestion of food in individuals whose habits are sedentary and whose digestions are active or it may come from an inherent abnormality of metabolism dependent upon ductless gland disease. It is very common in castrated animals. The obesity of overeating is always of milder type than that associated with endocrine disturbance.

So far as is known there are two main disorders of fat metabolism—the failure of the diabetic to form fat from glucose, and acidosis, the inability of the organism to burn fat beyond betaoxybutyric acid, acetoacetic acid, or acetone. The symptoms are unsteadiness of gait, stupor, coma, air hunger, in all of which the essential features are due to the impoverishment of the body in available bases. In infants this frequently follows an excessive fat diet. It is also common in starvation due to the deprivation of sugar. It is associated with phosphorus poisoning, narcosis, carcinoma, liver disease, inanition, etc. It has been produced experimentally by the administration of acids or by foods deprived of their bases. The excess of acid in the body whether produced in the body or introduced from without must be neutralized in part by the ammonia manufactured in the ultimate metabolic transformation of the protein and by the alkaline salts of the blood and tissues. When alkali is reduced the carbon dioxide accumulates in the tissues, blocking oxidation. The urine immediately shows an increase of ammonium salts, a decrease of the urea and an increase in the output of sodium, potassium, calcium and magnesium, which last two are drawn from the bones.

Symptoms do not arise until the fixed alkalies are exhausted; and they are immediately relieved by the administration of alkalies, except in those cases of starvation where the administration of sugar and the subsequent sparing of the fats relieves the situation. In herbivores, acidosis does not follow starvation, but, on the other hand, it is markedly easier to excite it in herbivores than in carnivores whose heavy protein diet produces more ammonia, which better enables the animals to protect their fixed alkalies. The acid intoxication of infections arises from different causes and is dependent on the intensity of the type of infection; but ultimately it also depends upon the depletion of the fixed alkalies.

IRREGULARITIES OF PROTEIN METABOLISM.

Fat and carbohydrate disturbances are not infrequent in carnivores, but it is with the protein fraction of the diet that most of the trouble is connected. Natural foods contain several proteins or groups of proteins, whose biological adequacy depends upon their yield of aminoacid. Experiment has shown that many proteins are entirely lacking in one or more of these essential radicles; and no food can be adequate unless it contains at least all the aminoacids that the individual animal is unable to manufacture for itself. So far as is known, no animal can produce in itself either lysin or tryptophane. Gliadin, the principal protein of wheat and lacking in lysin, is unable to support growth even when given in amounts sufficient to insure the storage of nitrogen, and is associated with a diet adequate in all other factors. Absence of tryptophane prevents not only growth but maintenance. Any of the aminoacids, whose radicles are contained in tissue proteins, may contribute to the maintenance of adult equilibrium; but no growth occurs unless all the necessary groups are present. Except in laboratories, diets are never made up of isolated proteins, but they are often composed of proteins derived from one plant and are often deficient. McCollum and his associates in their studies showed that while there were pronounced differences in the composition of many foods used by men and animals not only in their protein content but in water, fats, carbohydrates, etc., yet in the combinations found even in rather restricted diets, the errors, as a rule, corrected each other.

During digestion the protein molecule is broken down into the component aminoacids which are absorbed and synthesized in the intestinal walls, and appear on the other side as the specific blood protein, which serves as the substrate for the anabolism of all the special tissue proteins. Excessive protein is stored to a slight extent as aminoacid for the future maintenance of the blood protein, the integrity of which is tenaciously protected during hibernations, sexual migrations, and even during starvation. The animal body tends to adjust its nitrogen metabolism to its nitrogen supply; the adjustment requires an appreciable amount of time. A diet changed to a lower nitrogen level results in a continued loss of nitrogen, increased combustion of fats and carbohydrates. The animal makes no apparent effort to reëstablish equilibrium, and sooner or later digestive disturbances and loss of strength occur.

If, on the contrary, the protein is steadily increased after an animal has established equilibrium, the nitrogen metabolism increases and the level of nitrogen equilibrium rises to higher and higher levels. There is, at the same time, a lowering of the fat combustion, an increase in the respiratory quotient and in the heat production. The excess protein must be split, deaminated, burned and eliminated. Fifty-five per cent. of the intake is converted into glucose which is burned and the excess stored as glycogen. The sulphuric acid formed during the protein cleavage is neutralized by the body alkalies. In these cases the liver is often congested and enlarged. The urine shows excess of urea and ammonia. At times the excess, being so great that it cannot be absorbed, undergoes chemical and bacterial decomposition which causes digestive disturbances, torpor and constipation.

The organisms associated with protein food are usually the putrefactive types which break the protein molecule into the aromatic bodies, phenols, indolacetic acid, indolpropionic acid, skatol, etc. These bodies on absorption are believed to give rise to hypertrophy of the adrenal, interstitial changes in the kidney, and arteriosclerosis. Another group of substances, pressor bases and amines, are manufactured by certain anaerobes acting on proteins. These, when fed by mouth, are detoxicated by the liver cells, but when formed below the portal circulation, give rise to anaphylactic phenomena—urticaria, etc. Certain other organisms give rise to soluble toxins as in botulism and thyrotoxicon poisoning. All these types of toxins will destroy if they act acutely in sufficient concentration; or as is more common, if they act persistently over long periods, or at oft recurring intervals they will cause serious injury to the tissues coming in contact with them, and have a part in the production of cirrhosis of the liver, chronic nephritis, myocarditis, arteriosclerosis, etc.

All foods have a limit beyond which they are excreted untouched or imperfectly oxidized. Many of these partial oxidation products of protein are in themselves toxic and may also be a source of these degenerative organ conditions. The pathological material studied by us showed a marked decrease in gastrointestinal diseases in close association with the more hygienic care of the meat foods.

Always associated with the protein foods are the nucleoprotein complexes, which are split by both bacteria and digestive juices into globulins and nucleic acid, and then through the agency of a special enzyme, into purin bases and uric acid, in which forms they are excreted in the urine and feces. The oxidation of purins is never complete.

Gout, representing the pathology of purin metabolism, is a paroxysmal inflammatory disturbance, due to the deposition of sodium urates in the joints or in the internal organs, usually accompanied by a fibrosis especially in the liver, kidney, arteries, etc. The disease occurs almost exclusively in birds. Isolated cases have been described in dogs, horses and hogs, but among lower animals it is undoubtedly very rare. In birds it is most frequent in the carnivores—4 per cent., as against 0.02 per cent. in all other groups. It is higher in fish-eating birds than among the flesh-eaters. The avian gout is usually of the visceral type and was most marked in its distribution over the organs in the Anseres and Psittaci, birds whose diet apparently is not unduly heavy in nucleoproteins, but whose tract approaches the carnivorous type. The only arthritic cases occurred in Boat-billed herons (_Cancroma cochlearia_), fish-eaters. Our records show examples in Accipitres, Galli and Columbæ, although the number of cases in the last order were few and slight in extent. This disease stands in close relation to diet, as it develops on generous protein food, high in nucleoprotein or hypoxanthin, especially if this be associated with restricted activity.

The carnivorous mammals lead in the disease of the thyroid glands. Thyroid disease occurs among the birds, but is equally distributed among the dietary groups. Thyroid activity has a marked influence on metabolism probably through the influence of the iodine-containing protein of its secretion. There are some experimental evidences in favor of a detoxicating function of the thyroid, of which the following are quoted: (1) The effects of thyroidectomy are most marked in the carnivores; Herbivora are often capable of several years of life without thyroid tissue; (2) administration of meat to thyroidectomized omnivores or herbivores caused a marked increase in all symptoms. The importance of the relation of the meat diet, detoxication and thyroid disease receives considerable confirmation from the fact that among the 1,860 mammalian postmortems thyroid disease occurred in 2.6 per cent. of all mammals, 94.9 per cent. of which were found in flesh eating varieties. Wells[88] suggested that possibly this could be interpreted as an indication that toxic materials found in the meat in the intestinal tract were, under normal conditions, detoxicated by the thyroid. Against a local neutralization, however, is the improvement following the administration of dried thyroid substance. The function is either neutralization of toxic substances or the stimulating action on intracellular metabolism, both of which might be called into play by an excessive protein diet.

THE CARNIVOROUS DIET.

The pathology of the more prominent diseases developed in carnivores points at least to diet as a predisposing or determining factor. This diet is very high in a distinctly putrefactive protein and yields products, chemical and bacterial, which are toxic and which give rise to acute or more often chronic diseases of the alimentary tract and its adnexa. By reason of the amount ingested, excessive because of lack of exercise, there is a severe tax on the storage organs and on the detoxicating glands, as the liver and thyroid. The constant absorption of these toxic substances gives rise to chronic degenerative or fibrotic changes in the organs through which they pass: liver, kidneys, arteries, heart. In birds the degenerative diseases are even more marked than in mammals on the same diet. The ultimate fault of this diet, especially for mammals and birds with restricted activity, lies in the production of toxic bodies, produced either in the incomplete degradation or oxidation of the protein molecule or as the result of bacterial action on the protein molecule, a poisonous quality which is probably enhanced by the chemical changes occurring while the digested protein is passing through the intestinal mucosa. Garden conditions are such that these factors are almost unsurmountable unless the substitution of vegetable protein could be accomplished. Failure is often caused by limited feeding to carnivores of muscle and bones, whereas they should be supplied with glandular organs and blood.

THE HERBIVOROUS DIET.

Herbivorous diet must be divided into two groups, (1) that composed of succulent vegetables, and (2) of grasses, grains and seeds. In the first group there is an apparent variation in the results found in mammals and birds. In both there is a marked decrease in the chronic degenerative pathology. In both, acute gastritis is more prominent, far outstripping the incidence of this condition in other classes.

This diet yields a large and quickly available amount of carbohydrate which in conjunction with the moisture, heat and bacteria which are unavoidably associated with raw vegetables, makes an ideal situation for infection. These foods carry many saprophytic bacteria, moulds, etc. In birds the conditions are aggravated by the injuries that may occur from the sharp objects picked up with the gravel. The incidence of acute infection is higher among birds than among mammals of this group, and often there is involvement of the whole tract. The explanation of the other pathological findings occurring among birds must be found in the frequently repeated low grade infections which result finally in the production of chronic lesions in the digestive tract, liver, pancreas and kidney. Toxins as an etiological factor cannot be altogether excluded, but as a rule they are not important because the by-products of vegetables are distinctly less toxic than those derived from animal sources. Arteriosclerosis is much less frequent and less intensive in herbivorous birds than among the carnivorous, probably because of differences in the concentration and character of toxins in the two groups.

SOFT HERBIVOROUS DIET.

The diet of succulent vegetables is composed of tubers, edible roots and leaves. The tubers and edible roots are high in water and carbohydrate and poor in the amount and quality of the protein, most of which is not even a true protein but a mixture of aminoacids. The leaves, on the contrary, are rich in organic ash, especially calcium, sodium, chlorine, and fat soluble A vitamine, and as a rule contain a good quality of protein. They often, however, contain injurious substances. This diet, while measurably less nutritious than that of the carnivores, can satisfactorily nourish many animals with an extensive intestinal tract during growth and even throughout their entire life, but proves entirely inadequate when fed to an omnivorous tract.

SEED DIET.

Closely allied in general character to the diet of succulent vegetables are the seed diets, eaten only by birds and having no parallel among mammalian foods. All seeds, in contradistinction to tubers, contain true proteins which, however, are of poor quality because of the deficiencies in the aminoacid content. They are as a rule low in the fat vitamines and in the amount of calcium, sodium and chlorine carried. In three pathological conditions only do these birds show any oversusceptibility: (1) Sore eyes, (2) acute enteritis, (3) osteomalacia. Sore eyes were frequently noted in this group. The lesions were very like those described in animals deprived of the fat vitamine, which was present in this food in very small amounts or entirely absent, thus giving a very plausible explanation of this condition, especially as in some of the cases no other cause could be found. Gastric disease of any type is rare in this group because the food at the gastric stage is highly resistant to bacterial action. In the duodenum, however, the conditions are early changed because the bacteria carried with the food through the stomach become active in the presence of available carbohydrate and protein decomposition products.

Osteomalacia is confined almost as exclusively to the seed-eating birds as it was to the omnivorous mammals, and it is also associated with the same deficiencies, calcium and phosphorus (cf. Tables 19 and 20). It is also interesting to note that these two diets, the omnivorous and seeds, yield the greatest number of cases of tuberculosis. Mammals showed 32.6 per cent., as against 5.8 per cent. in all the other dietary groups, an observation which becomes more striking when man is added to the omnivorous group. Seed-eating birds showed 17.2 per cent., as against 6.4 per cent. in other groups. In both diets the fat, fat vitamine and inorganic salts, especially the calcium, are deficient in amount. In the wild, birds vary their diet of seeds with insects, worms, soft fruits and the tender shoots of plants, and at the same time they increase their inorganic intake by the minerals picked up with the gravel and from the water which has penetrated the soil.

GRAIN AND GRASS DIET.

The hay-eating animals constitute a large and well studied group— including practically all the domestic varieties. Table 19 shows that these animals yield the greatest number of cases of malnutrition, food poisoning, acute pancreatitis, acute degenerative conditions of liver and myocardium.

Recent literature describes many cases of osteomalacia, especially among horses and cows, in the famine districts of Europe. In our collection of 1,860 postmortems only one case was found, that of an Isabelline gazelle (_Gazella isabella_), a hay-eating animal, and in this case it was secondary to infection.

Arthritis, occurring in 3.4 per cent. of all the autopsies, was almost entirely confined to the hay-eating animals. The literature describes many cases of arthritis almost entirely confined to ungulates, of which many were associated with calving and subsequent infection. Bacteriological researches have found it most often associated with streptococci, staphylococci, or Bact. perfringens, organisms that require a certain amount of carbohydrate for their proper development. The relation of diet to this condition probably lies only in the fact that it provides an excessive carbohydrate substrate suitable for the optimum development of these organisms. Folin and Bergland, noting glycoresis in Herbivora, thought that it represented the absorption and excretion of unusable carbohydrate, present in grains, vegetables, fruits, etc., and that it was sharply separated from the main carbohydrate metabolism. These products were absorbed from the blood exactly as they were ingested like lactose, dextrose, etc., are absorbed, but do not enter into the economy although they might cause disorders, especially forms of arthritis.

The grain foods are composed largely of carbohydrates (principally in the form of cellulose and starch) small amounts of protein and little or no fat. They have a very low nutritive index so that large amounts must be consumed to supply adequate calories. This food is constantly present, and during the enforced idleness of captivity is almost continuously eaten. Despite these facts, however, malnutrition is present in 2.2 per cent. of the animals on this food. Associated with the plentiful food and lack of exercise are overeating and pica. Overfilled stomachs occurred thirty-four times. They were limited to these mammals and to the seed-eating birds whose environmental conditions are practically the same. Pica or excessive appetite for abnormal food, is also more frequent in these groups, but is usually associated with badly balanced diets, and thus represents an effort on the part of the animal to supply its own deficiency. It is present in osteomalacic monkeys and has been reported in cattle from regions where osteomalacia is common and following crop failures where the rations are restricted. In cattle it very often accompanies food poisoning, especially that produced by ingestion of peat hay.

Disturbance of the alimentary tract and its adnexa occurs in two forms: (1) Infection which is quite common and involves the duodenum, pancreas and liver, and (2) toxic. Compared with other diets alimentary disorders are not frequent among grain feeders, despite the ease with which grass foods ferment and the great variety of organisms found in them such as moulds (aspergillus), Bact. coli, paratyphosus, enteritidis, suipestifer, oidium lactis, etc. Few bacteria can attack whole protein, cellulose or starch, and the decomposition products, peptone, glucose, etc., are not available in any quantity until the lower stomach and duodenum are reached. The inflammation of the alimentary tracts of these animals is confined to the fourth stomach and duodenum, with, in many cases, extension to liver and pancreas.

Acute and chronic degenerative changes occur very frequently, and as a rule are the result primarily of absorbed toxins. After ingestion of new hay this often appears. The toxic substance probably is a terpinol ester, cumarin, which is produced by an enzyme in the cut grass.

The result is a gastroenteritis with jaundice, thirst and marked flatulence. It is very probable that many of the gastrointestinal and degenerative lesions are the result of the combined action of toxin and bacteria.

FOOD POISONING.

Food poisoning occurs in all diets, but especially among the grass- eating mammals. To-day under the general heading of food poisoning are included those cases due to (1) some injurious substance inherent in the food itself, true food poisoning, (2) those due to toxic substances liberated or produced in food contaminated by parasites or bacteria, (3) those due to bacteria that are carried by food and develop into true infection after ingestion. Most of the cases of meat poisoning described in literature undoubtedly belong to this third class, _i.e._, flesh is infected during the life of the animal or during its preparation for food and the virus develops in the host after ingestion. A fourth and more rare class of food poisoning is due to the condition of the individual consuming the food-protein sensitization.

Injurious constituents of normal flesh foods are very uncommon. There are a few poisonous fish, notably the balloon, puffer, and Fuga fish of Japan, which when eaten give rise to cholera-like conditions ending in convulsions and paralysis. A marked intoxication has been described in dogs which have fed upon the Greenland shark. Some fish are poisonous at certain periods as spawning season, the poison then being confined to the roe. Still others are harmless unless rendered toxic by some injurious food. This poisoning of muscle meats is seen in quail and partridges fed on mountain laurel, in some fish after consuming certain marine plants, and in cattle poisoned by amanita.

The most common sources of poisoning are spoiled meat and flesh of diseased animals, both of which are serious factors in the production of the gastrointestinal disorders of omnivores and carnivores. Practically all the reports of meat poisoning from the literature have been traced to the use of raw or insufficiently cooked flesh, and have yielded on bacteriologic examination _Bact. paratyphosus_, _Bact. enteritidis_, _Bact. suipestifer_, _Bact. coli_, or _Bact. proteus_.

The bacteria may produce toxin in the food previous to ingestion causing in the host only a severe intoxication. This is the situation developed after eating sturgeon infected with _Bact. piscidus agilis_, an organism which manufactures a highly poisonous alkaloid. A similar intoxication follows the ingestion of potatoes infected with _Bact. proteus_ or containing the poisonous alkaloid, solanin, which is produced in diseased and sprouting potatoes. Other examples of this are (1) ergotism—due to an infection of rye and wild grasses with _Claviceps purpurea_ which produces three poisonous bodies, ergotinic acid, which is not poisonous when taken into the stomach, sphacetinic acid and cornutin which act on the nervous system, brain, cord, vagus and vasomotor centre giving rise to toxic polyneuritis, and (2) favus, an acute febrile anemia with jaundice and hemoglobinuria probably due to a bacterial infection or fungus growth of the bean. Infected food may also produce soluble heatresisting toxins that produce immediate symptoms and increase the animal’s susceptibility to infection. This is the more common finding in cases of poisoning with milk and milk products. Non- pathogenic saprophytes carried in milk produce (1) a poison closely allied to tyrotoxicon, (2) a toxalbumin which in itself causes serious disturbances. Botulism, also probably of this group, is a disease initiated by a toxin elaborated by _Bact. botulinus_ acting on a protein. There is, however, some evidence that _Bact. botulinus_ can also establish a real infection.

The toxemias from food infected with bacteria may not occur until the food is ingested or the bacteria implanted. This result occurs in infections with _Bact. bovis morbificans_, Gärtner’s bacillus, etc., or after the feeding of meat from animals infected with _Bact. paratyphosus_ and _enteritidis_.

The plant poisons are more frequently due to inherent injurious substances, although even among them, bacterial and fungus diseases play an important rôle. Among the 16,673 plants indigenous to North America, almost 500 are more or less poisonous and about 30 are of great economic importance. The toxic factor may be confined to the leaf, seed or root, but more often it is associated with all parts of the plant. Through the efforts of the Department of Agriculture a more or less complete list of the plants implicated in the poisoning of stock has been compiled. This list includes the following: _Amanita muscaria_; _A. phalloides_; _Veratrum viride_; _Phytolacca decandra_; _Agrostemma githago_; _Delphinium_, 25 varieties; _Astragalus mollissimus_; _Aragallus lambertii_; _Crotalaria sagittalis_; _Euphorbia lathyris_; _E. marginata_; _Rhus radicans_; _R. diversiloba_; _R. vernix_; _Aesculus pavia_; _A. hippocastanum_; _A. glabra_; _A. Californica_; _Cicuta maculata_; _C. vagans_; _Conium maculatum_; _Kalmia latifolia_; _K. augustifolia_; _Leucothöe catesbaei_; _Rhododendron maximum_; _Pieris mariana_; _Datura stramonium_; _Solanum nigrum_; _S. dulcamara_; _Helenium autumnale_; _Asclepias pumila_; _A. verticullata_; _A. galoides_; _A. mexicana_; _A. eriocarpa_; _A. speciosa_; _A. fremonti_; _Eupatorium agertoides_; _E. urticarfolium_; _Isocoma wrightii_; _Daubentonia longifolia_; _Senecio jacobia burchelli latifolius_.[89] Some of these as the Amanita are only occasional sources of disaster, but as they frequently involve man they are important. The _Amanita muscaria_ symptoms appear very soon after eating the fungus and consist of a deepening stupor. _A. phalloides_, on the contrary, starts with severe abdominal pain, cramps, discharges of blood and mucus and later convulsions. The meat of animals dying from fungus poisoning is distinctly poisonous. This transfer of poison to the muscles of the animal partaking of these plants occurs also in poisoning with Kalmia.

The other plants of this list are closely associated with the grass foods and are consumed usually when the food on a range is scarce. Some groups as the Asclepias contain a distinct neurotoxin and give rise to a condition known as trembles or staggers. It affects mostly cows and sheep, causing staggering, trembling gait, bloating and salivation and death with convulsions. There is marked congestion of alimentary tract, liver and kidney. In the cerebrospinal axis there are marked changes in the nerve cells of the medulla and spinal cord. The Purkinje cells show the effect of extreme fatigue. Other plants causing stiffness or weakness of the extremities, show on microscopic examination no definite lesions in the cerebrospinal axis. Loco weed—_Astragalus mollissimus_ and _Aragallus lambertii_—causes maniacal disturbances but no gross lesions. This weed in Colorado costs the state enormous amounts of money yearly.

Helenium poisons domestic animals by means of a toxic glucoside, dugaldin, which produces stiffness, salivation and nausea with mild depression (“spewing sickness”). The alimentary tract shows severe inflammation of the rumen and reticulum which may at times be hemorrhagic. The liver usually presents an interstitial hepatitis. This toxin is decidedly hemolytic. The effects of this plant are always permanent, total recovery being very rare.

The larkspur (25 different varieties), on the contrary, shows prompt recovery after treatment, but no establishment of toleration. These plants give rise to nausea, vomiting and great agitation and destroy many animals yearly. The poisons are included in four alkaloids, all spinal cord depressants resembling aconite in general character.

These poisonous plants all produce more or less gastrointestinal inflammation and practically all are destructive in their action on the liver, pancreas and kidney. It is impossible to form even approximate estimates of the damage done by them because of the general ignorance of the subject. The Division of Botany has been collecting for the past few years specific information concerning these plants, but the individual plants are not equally poisonous, and all animals do not show the same susceptibility to the poison. _Veratrum viride_, for instance, is eaten with relish by sheep and elk and is decidedly toxic for the horse. In many the toxic factor has not been isolated. Some, as Euphorbia, are poisonous only when fed in honey derived from its flowers.

The influence of diet on the general health of animals is very far reaching and very inclusive. Metabolic disturbances are undoubtedly at times the result of unbalance—deficiencies on the one side, excesses on the other, at times are probably much more the results of bacterial invasions aided and abetted by the food administered, at still other times are poisonous either in their own content or from the degradation products resulting from digestion or bacterial decomposition.