disease are used. Some endemic diseases are restricted to certain localities and seem in some measure dependent upon local conditions (of atmosphere, soil, etc.) for their continuance. These are called miasmatic diseases.

Infectious diseases are frequently described as local or general. Local infections are those that present specific pathologic change in a restricted part of the body; the general organism suffers more or less in consequence. Examples of this are erysipelas and diphtheria. General infections are marked by an immediately generalized disease, as in typhus fever or plague. Strictly speaking, most if not all of the so-called general infections are at first local. Among purely local infections might be named the diseases of the skin due to vegetable micro-organisms.

Entrance of Micro-organisms into the Body.-Bacteria may be inhaled or swallowed, may enter through abrasions in the mucous membranes or skin, and may be transferred in utero from the maternal to the fetal blood. The mode of entrance in individual diseases depends upon the nature of the bacterium, its habitat, and surrounding conditions. Some may enter in but one way; others gain access in any of the different ways. Details regarding this subject will be given in the discussion of special infections.

Animal parasites of various kinds act as causes of disease. This group of diseases is termed the parasitic diseases or invasion diseases. In some instances the clinical course is similar to that of infectious diseases (malaria, dysentery, trichinosis); in other cases the manifestations bear little resemblance to infections.

CHAPTER II.

DISORDERS OF NUTRITION AND METABOLISM. Food. In the life of the organism certain substances are needed for the repair of tissues consumed in the wear and tear of life and to supply heat and other energy. Among these foods are proteids, carbohydrates, fats, inorganic salts, and water. A continuance of normal existence requires more or less definite proportions of the first three and at least a sufficiency of salts and water. The amount of food and the exact proportions vary somewhat in individual cases and under varying circumstances. Voit found that a laboring man under ordinary conditions requires 118 g. of proteid, 56 g. of fats, and 500 g. of carbohydrates. The proteids of the diet are necessary to restore tissue-waste, since the organism cannot build up proteids from simpler compounds. This consumes part of the nitrogenous foodstuffs. The rest, with most of

the fats and carbohydrates, is mainly useful in contributing

energy.

Diminished Supply of Food; Inanition; Starvation.— Either the want of food or disorder of the gastro-intestinal tract may lead to insufficient nourishment. This causes a loss of body weight, as the necessary heat-producing and energy-giving substances must be supplied to maintain life, and the tissues are consumed for this purpose. The carbohydrates (glycogen of liver and muscles) and fats suffer first and most profoundly, and unimportant parts are reduced before the vital structures are attacked. The subcutaneous and other adipose tissues and the muscles first waste, then the liver, bones, heart, etc.

The functions of various organs suffer greatly: the respirations and heart-action are weak, muscular exertions are reduced to a minimum, the endurance and nervous force decline, the bodytemperature sinks, and finally death may occur from exhaustion or secondary affections consequent upon the disturbed nutrition (see Acid-intoxication). The blood in starvation preserves its corpuscular richness surprisingly, even after prolonged abstinence. This is doubtless due to loss or evaporation of liquid; the actual number of corpuscles probably suffers reduction.

Increased Supply of Food; Overfeeding.-The effect of this depends upon individual conditions, such as the amount of exercise, the surrounding temperature, and less easily demonstrable peculiarities of the individual. An excess of proteid food leads to increased excretion of the end-product of its metabolism-urea. A very small proportion may contribute to building up a reserve amount of albuminous tissue; this has not been positively proved. Great excess of proteid eventually disturbs digestion and leads to its discharge with the feces.

The carbohydrates and fats are broken up in the body and excreted mainly as carbonic acid and water. An excess of these foods tends to cause increased deposition of reserve fat and glycogen, which may be called upon at subsequent times of need. This deposition is a normal or physiologic process and has the distinct purpose just indicated. Exceptionally in the condition called obesity the storing up of fat is inordinate and probably pathologic.

Obesity. The origin of fat is still a subject of controversy among physiologists. According to the oldest view, which, however, is still adhered to by some, and has indeed been strongly defended, the fat of the body is derived from that of the food, and the possibility of this has actually been demonstrated. Under ordinary circumstances, however, but little of the fat is so produced. Another school of physiologists maintained that the proteids of the food break up into a nitrogenous and a non-nitrogenous part, the former being finally excreted as urea and other substances or repair

ing the tissue-waste, the latter part contributing energy or forming fat. At the present time it must be admitted that though proteids may possibly form fat in this manner, the actual demonstration is still wanting. The main source of fat is certainly the carbohydrates of the food.

Causes of Obesity.-Excessive ingestion of food by persons having active digestion and leading sedentary lives may occasion unusual deposition of fat. It is difficult, however, to determine the limits between physiologic and pathologic fatness. In some cases patients assert that the amount of food has not been excessive, and this may be actually true. Obesity in such individuals is undoubtedly pathologic and due to some inherent abnormality of metabolism. A further proof of the existence of such a tendency is seen in certain families, in which excessive fatness is common, even in childhood. The nature of this metabolic disorder is obscure. It has often been held that the power of oxidation is lacking, and, as a matter of course, the amount of oxygen consumed is deficient in comparison with the amount of food ingested. This must be true, or the fat could not accumulate; but it remains to be shown whether the diminished oxygen-consumption is the primary cause or only an incident in the disease.

Pathologic Anatomy.-The excessive adipose tissue in this disease is found in the skin and subcutaneous tissues, in the omentum and peritoneum, around the kidneys, heart, and mediastinal tissues, in the liver, and less commonly elsewhere. The amount varies from slight excess to monstrous deposits. Secondary changes in the organs (notably the heart-muscle) may be due to pressure or functional inactivity.

Associated Conditions.-Fatness is more or less closely related to certain other diseases of metabolism, such as diabetes and gout. Anemia is frequently present and has sometimes been regarded as a cause, operating by reducing oxidation. (Further discussion of this subject is included under Fatty Infiltration.)

Excessive Tissue-destruction.-This has been referred to in connection with inanition; but it may occur as a condition independent of the amount of food ingested. Among the conditions in which this is observed may be mentioned fever, infectious or of other forms; chronic infectious diseases, with or without fever; tumors, especially carcinoma; intoxications of various sorts; some cases of Graves' disease, etc. In all of these conditions the fats of the body may waste as in simple inanition; but there is an early and marked tendency to consumption of the more important proteid structures. This latter consumption may proceed along physiologic lines, or there may be distinctly pathologic modifications sometimes leading to serious results (see Acid-intoxication).

The nature of the metabolic disturbances in these cases is obscure, though it is likely that toxic substances of various sorts are

the direct causes. This is most probable in the case of direct intoxications (phosphorus), but is also likely in other cases. In Graves' disease and carcinoma, as well as in fevers, there are doubtless poisonous substances in the blood, but whether these are the causes of the metabolic changes or not requires further study. The fact that thyroid extract is capable of causing excessive destruction of tissue in normal or obese persons is significant in this connection.

Acid-intoxication.-In the final metabolic transformation of proteids there are produced ammonium, urea, kreatinin, and other nitrogenous substances. The formation of urea is still obscure in some particulars. It is certain that a large part is produced in the liver, and it is probable that some is formed in the muscles. The intermediate steps in the manufacture of urea have not been definitely determined, but it is known that the liver is capable of converting ammonium salts directly into urea, and it is probable that ammonium is an important intermediate product of proteid transformation. An excess of acids in the body (either from introduction from without or production in the body) is in part neutralized by alkaline bases in the blood and tissue-juices, and in part by ammonium. In consequence of this consumption of ammonium the urea of the urine decreases and the ammonium salts are increased. The quantity of such salts is therefore in a measure an indication of the condition which has been termed acid-intoxication. The partial neutralization of acids by the fixed alkalies of the body causes reduced alkalinity of the blood and juices of the body.

Experimental acid-intoxication is easily produced in animals by feeding them with foods deprived of alkaline bases, or by direct administration of acid. In the former case the acids (sulphuric from the sulphur of albuminous food; and phosphoric from the phosphorus) resulting from transformation of food and tissues must be neutralized by the alkalies of the body and the ammonium produced in the process of urea-formation in the liver; in the latter case there is direct excess of acid. Such acid-intoxication is readily produced in herbivorous animals, as the amount of proteid food is small, and in consequence but little ammonium is produced. Various nervous symptoms are observed. The animal breathes quickly, the pulse grows rapid, muscular weakness, ataxia, and tremor develop, and finally coma or collapse terminates the disease. The administration of alkalies may completely arrest the progress of the condition, and full restoration may occur.

Acid-intoxication in Man.-Somewhat similar symptoms are seen in man in certain diseases in which decreased alkalinity of the blood and increased elimination of ammonium, with decrease of urea and the excretion in the urine of certain organic acids, have been discovered. The assumption is warranted that these are cases of acid-intoxication.

Etiology. Among the conditions in which this occurs are fever, diabetes, carcinoma, acute yellow atrophy of the liver, severe anemia, phosphorus-poisoning, advanced gastro-intestinal disease, and inanition. Sometimes no discoverable cause can be detected (cryptogenetic acid-intoxication). Gastro-intestinal disorders are very likely the occasion of this form of obscure acidosis. Poisons produced in the intestines probably set in play the metabolic disturbances which terminate in over-production of acids.

Among these acids are lactic, sarcolactic, sulphuric, phosphoric, diacetic, and 3-oxybutyric acid. These in part combine with the fixed alkalies and with ammonium, and in part are excreted as such. Some, as sarcolactic acid, usually suffer decomposition in the body, and are therefore rarely met with in the urine.

The origin of the acids of the fatty acid series has been the subject of much controversy. Undoubtedly they may be derived from the non-nitrogenous part of proteids, and in most of the diseases above enumerated this is probably the case; but they may be formed from carbohydrates as well. The increase of diacetic and 3-oxybutyric acids in cases of diabetes when small amounts of carbohydrates are supplied, and their decrease when the carbohydrates are increased, point to the fact that destructive consumption of proteids is the important source, though it may not be the only or invariable source.

There is always reduction of oxidation in cases of acid-intoxication, but it is not known whether this is the primary disturbance, or whether it is but an accompaniment. Experimentally it has been shown by several observers that diminution in the supply of oxygen will lead to increase of these acids. They probably owe their presence to excessive production and to the failure of the normal oxidation which would reduce such bodies to simple excretory products. Other substances may result from the same. tissue-destruction with insufficient oxidation. Among these are the amido-bodies, leucin and tyrosin, found in the urine in phosphorus-poisoning and acute yellow atrophy of the liver as well as in other conditions.

Symptoms. The symptoms of acid-intoxication in man may be quite similar to those seen in experiments upon animals. Marked dyspnea (air-hunger), rapidity of the pulse, depression, stupor, and deep coma (coma carcinomatosum, diabeticum) are some of the more pronounced manifestations. The production of these may be direct or indirect. The cause of these symptoms is very probably the acid-intoxication due to the presence of 3-oxybutyric acid. Diacetic acid and acetone are derivatives of 3-oxybutyric acid. Aside from such direct action, acid-intoxication may effect its results by lessening the alkalinity of the blood and abstracting fixed alkalies from the fluids of the body.

Formation of Albumoses.-In disturbed conditions of metabolism albumoses, or probably very rarely peptone, are formed.