Energy Metabolism of Brain in Human Protein-Calorie Malnutrition

Abstract

SummaryCerebral blood flow (CBF) and carbohydrate metabolism were studied in 5 normal children and 25 children, aged 40 months or less, with varying degrees of protein-calorie malnutrition (PCM). CBF in normal children and those suffering from grade I PCM was 90.3 * 5.7 mVlOO glmin, a value comparable with that obtained by other investigators, but the proportion of glucose taken up by the brain which combined with oxygen, the oxygen/glucose index (OGI), was 65.8%, indicating significant conversion of glucose into lactic acid. Cerebral lactic acid production was 45.3 pMI100 glmin, and the respiratory quotient (R.Q.) was 1.00. With increasing severity of PCM, there was increased glucose utilization and a progressive reduction in the OGI. In grade IV PCM, CBF was 68.7 * 5.4 mUl00 glmin, and the OGI was 34.7%. Cerebral lactic add production was 27.4 pM/100 glmin, and the R.Q. rose to 1.52. These findings suggest that in severe human PCM the proportion of glucose ~d e r g o i n g aerobic oxidation is reduced, and that in addition to being converted to lactic acid, a significant proportion of glucose is transformed by the brain into long chain fatty acids. SpeculationThese results indicate that in chronic, severe PCM, a considerable proportion of glucose utilized by the brain is converted into fatty acids. This alteration in cerebral carbohydrate metabolism may be due to altered function of one or more of the regulatory enzymes w i t h the brain. Acetyl coenzyme A carboxylase, fatty add synthetase, and the hexose monophosphate shunt dehydrogenases are some of the more obvious candidates for future investigations.Protein-calorie malnutrition is characterized by a variety of neurologic and behavioral symptoms (14, 15). Apathy, withdrawal, and lack of interest in surroundings are the most constant and earliest neurologic features of the condition, and are common in children whose weight is less than 40% of the expected value (29). The electroencephalogram is usually diffusely slowed during the acute stages, returning to normal after nutritional recovery (1 3).Long term studies on children who have experienced PCM early in life demonstrate a variety cf cognitive inadequacies. These result in defective intersensory organization and poor school performance (5,6,8,22,26). As a rule, the younger the child at the time of his hospitalization for malnutrition, the less likely is he to achieve ultimate intellectual parity (4).Numerous experimental studies have been designed to reproduce the clinical picture of PCM. The brain of an animal subjected. to nutritional deprivation in the course of development weighs less, contains fewer cells, and has lesser amounts of protein, nucleic acid, and myelin than the brain of a well nourished animal (l0,21,31-34). From these studies, it has become evident that when nutritional deprivation occurs at the time of the brain's "growth spurt" these alterations are maximal and irreversible (1 0).In order to correlate the data gathered from experimental animals with clinical experience, we undertook...

Metabolism of Sulfadiazine in Children with Protein Calorie Malnutrition

“…In severe human PCM (marasmus), oxygen consumption is diminished (16). Recently, it has also been observed that a similar situation exists for the brain (17). It is thus possible that the constraint of oxygen consumption affects the process of acetylation as well.…”

Carbohydrate as nutrient in the infant and child: range of acceptable intake

“…This is in part the consequence of lack of easy accessibility of this organ for such studies. Previous studies have quanti®ed oxygen and glucose consumption by the brain in anesthetized or unanesthetized children using Fick's principle (Settergren et al, 1976(Settergren et al, , 1980Mehta et al, 1977;Kennedy & Sokoloff, 1957;Kennedy, 1956;Sokoloff et al, 1977). Arterio-venous gradients of glucose, oxygen, lactate, pyruvate and ketones were measured across the brain.…”

“…It should be underscored that such computation assumes that oxidation is the only fate of cerebral glucose uptake, and that glucose is the only oxidative fuel being utilized by the brain. The last two assumptions are appropriate, considering that the contribution of ketones, except in prolonged fasting in adults, is small and that non-oxidative disposal of glucose, that is, release of lactate and pyruvate by the brain, is also small (Settergren et al 1976(Settergren et al , 1980Mehta et al, 1977). Recently, cerebral metabolic rate of glucose has been quanti®ed in children and adults using positron emission tomography (PET).…”

Lactate as a Cerebral Metabolic Fuel for Glucose-6-Phosphatase Deficient Children

“…We, therefore, wondered whether in some patients, besides glucose, lactate might be utilized as an energy substrate by the brain and thus protect the child against the deleterious effects of glucose depletion. This would be opposite to the situation in normal children (18,22,24,25,26) and normal adults (4, 9, 23), in whom the brain releases lactate and consumes ketone bodies (P-OHB and AcAc) as soon as glucose, the preferential fuel, becomes insufficiently available. In G6Pase-deficient children, however, this is impossible because there is no physiologic hyperketosis during fasting.…”