Part 42

Iron is the essential element of hemoglobin and chromatin—the body constituent most directly concerned with the process of oxidation, secretion, reproduction and development. The iron of the food is absorbed from the small intestines, enters the circulation through the lymphatics, is deposited in the liver, spleen, and bone marrow and eliminated through the intestinal walls. There is very little iron reserve in the adult body; and as a result any failure of the intake to equal the output causes an immediate reduction of the hemoglobin. Voit found that the iron eliminated in the feces of starving dogs, or dogs on a diet low in iron comes from the body through the intestinal walls. Medicinal iron stimulates the production of hemoglobin and red blood cells but whether it is directly employed in the production of hemoglobins has not been proved. Undoubtedly most of the extra iron given with the food passes through the alimentary tract without being absorbed or metabolized. The greater the amount of iron in the food, the greater the influence of the inorganic iron. Anemia occurred in all the animals we examined at least four times as frequently in omnivorous as in all the other dietary groups, a fact probably explained by the low content of iron and calcium in this diet. Both Von Wendt[69] and Sherman[70] demonstrated that larger amounts of iron were required to maintain the iron equilibrium when the amount of calcium was low.

Herter has shown that many anemias are associated with intestinal putrefaction. The carnivores, however, on a diet that putrefies very easily and on one in which the iron content is apparently of distinctly lower nutritive value than that of the iron found in milk, eggs and vegetables, presented an anemic incidence of only 0.32 per cent. This is probably due to the excellent hygienic care of the meat foods and to the morphology of the carnivorous intestinal tract, which is short, straight and fashioned for quick elimination. The cases of anemia steadily increase among the animals as the conformation of the tract approaches the omnivorous type with the longer and wider hind-gut.

Herbivora, obtaining their iron from vegetable sources, are much less liable to blood disorders. The iron needs of the female are greater than those of the male because of the drains of pregnancy and lactation. Young animals demand more iron than adults. All exclusively breast- feeding animals have a considerable storage of iron in the body at birth, while those that eat food immediately have no such supply. Bunge’s[71] experiments showed that breast-fed animals contained about six times as much iron as the milk that nourished them. The iron content of all these animals is highest at birth, remains constant during the suckling period and then rapidly decreases to the adult standard. After this level is reached the iron metabolized must be supplied from the food if the hemoglobin is to be spared.

The functions of all these inorganic substances are intimately interrelated and in places interchangeable. Calcium is capable of correcting disturbances of inorganic equilibrium in the animal body whatever the direction of the deviation from the normal may be. These interrelationships are most involved in the maintenance of body neutrality. The normal processes of metabolism involve a continual production of carbonic, phosphoric and sulphuric acid which must be immediately disposed of if the neutrality of the body is to be permanent.

The factors involved in this are carbonates, phosphates, ammonia and proteins. Carbon dioxide is the chief excretory product but is at the same time a normal constituent of the blood and as such, is an important factor in this physicochemical regulation. There is a tendency for the respiratory mechanism to hold its carbon dioxide tension nearly constant. Late investigations have shown that lowering of this tension is an early sign of beginning acidosis. When food such as protein, is taken in excess the strongly acid residues are neutralized by the sodium and potassium carbonates which are eliminated with a corresponding loss of sodium and potassium. The carbon dioxide tension diminishes, 37.2 per cent. on a high protein as against 43.3 per cent. on a vegetable diet. If this excess is long continued, the result may be, and often is, an increased elimination of the base-forming elements which if not made good tends to diminish the body’s reserve alkalinity. A diet with a preponderance of basic elements leads to an alkaline urine with an increased uric acid solvency and an increased carbon dioxide tension and reserve alkalinity. A diet with a preponderance in the acid-forming elements, on the contrary, leads to an increased urinary acidity and urinary ammonia, decreased ability to dissolve uric acid and lowered carbon dioxide tension and alkaline reserve.

DEFICIENCIES OF VITAMINES.

Recent investigations have shown that diets furnishing sufficient amounts of protein, fat, carbohydrate and inorganic salts may yet prove inadequate for growth or even for maintenance. Hopkins,[72] feeding rats on purified food mixture was unable to obtain any growth until he added small quantities of milk or of the ether-soluble portion of milk but with this addition growth progressed in the normal manner, but it was out of all proportion to the energy or protein value of the addition. Five substances of this character, called by Funk[73] Vitamines, have been described, two of which have definitely established a place as essential food factors. According to him, pellagra, rickets, scurvy and beriberi are the result of a lack of these unidentified but specific and indispensable food complexes.

The first vitamine isolated was the fat soluble A, an adequate supply of which is necessary, not only because of its stimulating growth properties, but because its absence produces a serious condition of the eyes and, at times, marasmus leading to death. Xerophthalmia is a common condition in animals on experimental diets. The eyes are swollen, the cornea inflamed and often opaque while blindness and death invariably occur unless the dietary error is corrected. McCollum[74] rescued animals almost at the point of death by butter or other fat rich in this vitamine. Opacities of the cornea are often seen in the animals in this and other gardens among ungulates—hay-eating mammals; four advanced cases were found, three in seed-eating birds and one in a fox on a diet made up solely of horse muscle. The quantity of vitamine A present in muscle, hay and seeds is very small. It is supplied in largest amounts in milk, eggs, glandular organs and leaves, substances which were very low or absent in the diet of all the affected animals. This xerophthalmia has been reported in man on several occasions, especially by Hrdlicka[75] in American Indians, by Mori[76] in 1400 Japanese during a period of food shortage (this epidemic was cured by the addition of chicken livers to the diet), by Bloch[77] in forty-seven children of Copenhagen fed on a fat free milk who were cured by the administration of cod liver oil. The disease is not however a fat starvation, as it is entirely uninfluenced by vegetable fats which do not contain this vitamine.

Beriberi is an established deficiency disease, frequently seen among the poorer classes of the Orient whose diet is limited to polished rice and fish. It has appeared in Labrador coincident with the excessive use of bolted flour. A similar condition has been induced in pigs and cattle by a diet made up of an excess of cotton seed meal and tankage. Two forms of the disease are described: (1) acute or wet, characterized by marked edema, ascites, hydropericardium, hydrothorax, edema of the lungs, and a congestion of the spleen, liver, kidney, and heart muscle, (2) chronic or dry, characterized by polyneuritis. The disease was first produced experimentally in pigeons by Eijkman[78] in 1897 by means of a diet of polished rice. The paralysis appeared in 2–3 weeks after the diet was initiated. Fraser and Stanton[79] in 1907, found that it could be cured by an alcoholic extract of rice polishings. Funk[80] later determined the vitamine character of this extract. In pigeons and fowls experimental feeding usually results in the chronic or polyneuritic form, expressed by a typical degenerative inflammatory condition of the peripheral nerves. In pigs, on the contrary, Rommel and Vedder[81] produced both types, though the acute or wet beriberi appeared more frequently. In rats the same deficiency causes multiple hemorrhages in the cerebellum and midbrain followed by a degeneration of the associated nervous structures. It is possible that the pathology following a lack of the vitamine B or in fact any of the vitamines will vary with the different species or with varying demands of different individuals. This antineuritic vitamine affects more than the nervous system, and it is possible that all vitamines may have wider effects than are at present described.

Scurvy was the first condition to call attention to diet as a cause of disease. It occurs in man when deprived of fresh vegetables. That faulty diet was in some way the cause of scurvy has been known for many years, but only since 1905 has there been any systematic attempt to determine the peculiar value of the curative foods. At this time Theobald Smith[82] called attention to a disease suggestive of scurvy which developed in guinea-pigs fed on a diet of oatmeal. This observation was confirmed by Holst and Frölich[83] who stated that the disease could be prevented by the addition of fresh milk or cabbage, because in these foods there was present an antiscorbutic or C vitamine. This unidentified substance was easily destroyed or diminished by heat or an alkaline medium. It was found in rather large amounts in succulent vegetables and fruits. McCollum[84] and his coworkers showed that the oat kernel was low in inorganic salts and vitamine A and poor in the quality of its protein; but with these faults corrected it proved to be a complete food for rats. McCollum also found that scurvy developed more readily in animals if the physical properties of the diet favored constipation. He was able to delay the onset of the disease in guinea- pigs for a considerable period by the addition of mineral oil which has no food value, or phenolphthalein, a cathartic. At the same time, Jackson and Moore,[85] found the cecum of all guinea-pigs dying of scurvy, packed with putrefying feces. They were able to produce a mild type of the disease by the injection of the diplococci isolated from the swollen joints.

From these observations it seems safe to conclude that scurvy may not be purely a deficiency disease, or even a simple dietary one, although the presence of a vitamine influence is not excluded; but it is probably the result of a bacterial invasion of tissues debilitated by a faulty diet and by the toxins produced by the putrefactive bacteria developing in a diet unsuited to the anatomical demands of the alimentary tract. This theory receives support from the fact that pasteurization destroys all aciduric bacteria, allowing only the spore-forming putrefactors to develop; and from the fact that scurvy develops more frequently in children on stale pasteurized than on stale raw or boiled milk. In this Garden no suggestion of scurvy has been noted.

Pellagra is very definitely a disease of poverty endemic for years among the poor, especially in the mountains of Northern Italy. It has been under observation in the United States since 1907. So far as is known no cases have been observed among animals. Opinions differ as to the rôle of diet in the etiology but the results of recent studies seem to show that uncomplicated cases of average severity clear up entirely on a diet rich in animal protein. No vitamine deficiency has so far been determined. Wilson’s careful studies of the diets known to have produced the condition show that the etiological factor lies in a deficiency of the protein molecule. The results of Goldberger[86] corroborate this fact, and he concludes from his latest studies that “the dominating rôle of diet in the prevention and causation of pellagra is referable primarily to the character of the protein supply or to the specific quality of the aminoacid makeup of the protein supply.” Just what aminoacid or combination of aminoacids it is, has not been determined, nor has the possibility of a vitamine alone or in combination with the aminoacid factor been absolutely excluded.

The principal influence of the omnivorous diet is toward those degenerations arising primarily from imbalances in the inorganic makeup, or to insufficiencies of certain necessary factors. The vitamine deficiencies are markedly less prevalent in animals than in man whose food is less often consumed in its natural state. It is now known that much of the injury and loss of nutritive value in foods is produced by the processes involved in preparation, preservation, refinement and storage. Whenever the choice of food is not restricted, vitamine deficiencies do not occur. The vitamine requirements probably differ in different species and in individuals from the same species according to their environmental and individual variations. It is very possible that if the diet is low in vitamine content there may arise conditions of relative deficiencies; and McCarrison has shown that a vitamine deficiency associated with a high fat or carbohydrate content may disturb the balance of the endocrine glands. It is however to the inorganic content of the omnivorous food that most of the disturbances peculiar to this diet are to be assigned.

With the flesh eating animals and birds the records present a very different picture. Disorders of the digestive tube, of the storage organs, of the organs of elimination and of the endocrine glands predominate. Their diet is low in carbohydrates and, at times, in fats and very high in protein. Bone supplies the inorganic salts, which in this Garden is fed only to the larger mammals. The carnivorous birds get their inorganic supply from mice which are eaten entire. The carnivores are as a rule large and are given to active fighting or to long flights. In the wild, very probably there are long periods between feasts, while in captivity the food is always plentiful and regularly supplied. This regularity added to the lack of exercise, particularly among the larger animals, must lead to excessive demands upon the storage and eliminating organs. Storage is always promoted by rest and liberal diet, and cleared away by exercise and starvation. The life of these birds and mammals, moreover favors inactivity of the bowels, which, together with the highly putrefactive diet adds another serious factor to a problem which in gardens is almost insurmountable.

IRREGULARITIES OF CARBOHYDRATE METABOLISM.

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.