KETONURIA

KETONURIA, increased excretion of ketone bodies in urine. Ketone bodies (/3-oxymaslyanaya kislota, acetoacetic acid and acetone) are formed in intermediate metabolism during the breakdown of fats and fatty acids (maslyanaya, kapronovaya and their higher homologs with even number of C atoms), as well as from some amino acids. From carbohydrates and alcohol, ketone bodies apparently are not formed. When carbohydrate combustion does not occur in the organism, either because they are not introduced (with protein-fat food and during starvation) or because this ability is impaired (diabetes), increased excretion of ketone bodies by the kidneys and lungs is observed. Substances that inhibit the formation of ketone bodies include carbohydrates, glycerin, lactic, tartaric and citric acids, glutamic and aspartic acids, glutaric, saccharic and suberic acids, as well as glycine and alanine. Dietary fats have the ability to increase the formation of ketone bodies. Muscular work somewhat increases existing K.; its influence on K. is indirect, since physical work reduces carbohydrate reserves in the body. The site of formation of acetoacetic acid should be considered the liver, /3-oxymaslyanoy kisloty-along with the liver also other organs. The formation of acetone occurs almost exclusively in the lungs and in urine after its separation by the kidneys. The amount of /3-oxymaslyanoy k-ty in organs is higher than its content in the blood. K. and ketonemia are observed in people as physiological and as pathological phenomena. In a healthy organism capable of normally burning carbohydrates, combustion of maslyanoy k-ty through /3-oxymaslyanuyu to CO₂ and H₂O occurs. With insufficient combustion of carbohydrates, a delay or disruption of the breakdown of /3-oxymaslyanoy k-ty occurs, resulting in its accumulation; simultaneously, accumulation of acetoacetic acid also occurs. The larger part of these two acids is excreted from the body, partially turning into acetone. Many researchers considered K. as a result of carbohydrate restriction as a specific diabetic metabolic disorder and believed that K. in non-diabetics does not reach such a degree as in diabetics. This view is rightly disputed by a number of authors.-Significant or moderate ketonemia and K. can occur

KETOI

in two ways: either significantly enhanced formation of /3-oxymaslyanoy k-ty or delay in oxidation of normally formed k-ty (/3-oxymaslyanoy and acetoacetic). Apparently both factors participate in the process. The question of why with restriction of carbohydrate food, ketonemia and K. regularly appear in all individuals is also insufficiently clarified. Ketosis can occur as a result of increased fat metabolism. Landergren considers it possible for ketosis to develop in the process of sugar formation from proteins, therefore, perhaps in patients with severe diabetes, along with K., an increase in glycosuria and azoturia occurs. There is also an opinion that ketosis appears as a result of damage to liver cells, as well as cells of other parenchymal organs capable of destroying acetoacetic acid. All substances causing changes in liver cells, for example P, As, poisonous mushrooms, chloroform, alcohol, etc., contribute to the development of ketonemia and K. (Fishler, Wichert and Tsukershteyn). Ketonemia and K. are not in complete parallelism: with significant ketonemia, slight K. can be observed and vice versa.-Acids formed in the body bind the ammonia formed in intermediate nitrogen metabolism, leading to an increase in its content in urine. When large amounts of acid-reacting substances enter the blood, the active blood reaction remains almost unchanged due to the buffer properties (see) of the blood. In diabetics, the appearance of large amounts of organic acids leads to disruption of acid-base balance, the restoration of which is achieved to some extent with the help of a number of regulatory mechanisms (respiration, urination, liver function, blood properties). With a shift in blood pH toward acidity, practically no encounter occurs, and compensated acidosis is usually encountered, characterized by a decrease in alkaline reserve (hypocapnia) and alveolar tension CO₂. When such compensation becomes impossible, decompensated hypocapnia occurs, i.e., a shift toward acidity. This is observed during coma, before death.-Pathological K. is observed in diabetes, cancer of various organs, digestive disorders, febrile diseases, as well as various poisonings.-Ketonemia and K. vary in intensity depending on the severity of the disease, i.e., on significant or moderate disturbances of carbohydrate, protein and fat metabolism. Ketosis is also closely dependent on the food introduced. In mild cases of diabetes, it is possible to bring K. and ketonemia to normal with diet alone. In cases of moderate and severe forms of diabetes, ketosis in the blood and urine tends to increase. In cases of moderately severe diabetes, insulin can bring ketonemia within normal limits. In severe diabetics, only prolonged insulin treatment can reduce K.; the best results are obtained with simultaneous diet and insulin treatment. In some febrile diseases, in the acute period of lobar pneumonia, in severe cases of tuberculosis, in acute appendicitis, an increase in ketosis in the blood and urine is noted. In circulatory disorders, an increase in ketonemia and K. is noted only sometimes in cases with pronounced signs of decompensation (Tsukershteyn). Sometimes an increase in ketone bodies in the blood and urine is observed in liver diseases, especially in far advanced degenerative processes (Fishler, Tsukershteyn).