i8 5 6 



II WDI'.i ii iK Hi I'insli i| in.-, 



NEUROPHYSIOLOGY III 



in the brain characterized by unconsciousness and 

 a low cerebral metabolic rate, even long after the 

 restoration of an adequate cerebral blood How (39). 



oxygen deficiency. Although cerebral blood flow is 

 elevated by decreases in the oxygen tension of the 

 arterial blood, this compensation may be insufficient 

 to supply adequate amounts of oxygen to the brain 

 (101). The progressive menial disturbances resulting 

 from anoxia at high altitudes arc well known (127). 

 When the cerebral venous oxygen saturation drops to 

 approximately 24 per cent (corresponding; to approxi- 

 mately 15 mm Hg oxygen tension in the usual 

 cerebral venous blood), consciousness is lost (117). 

 Normally, the oxygen saturation and tension of 

 cerebral venous blood arc approximately 65 per 

 cent and 35 mm Hg, respectively . Mild mental 

 symptoms may, however, occur above the level of 

 unconsciousness even though no discernible change in 

 cerebral oxygen consumption occurs (101). It is 

 possible that despite a normal rate of oxygen utiliza- 

 tion, normal energy transfer does not occur at such 

 low oxygen tensions in the brain. It is more likely, 

 however, that mental symptoms short of uncon- 

 sciousness can result from disturbances in areas of 

 the brain SO small that changes in their oxygen con- 

 sumption are not reflected in measurements of the 

 brain as a whole. Increased arterial oxygen tensions 

 as high as those produced by the breathing of oxygen 

 at 3.5 atm., a level close to the point of oxygen 

 toxicity, is also unassociated with any change in 

 cerebral metabolic rate (108). 



Reduction in cerebral oxygen consumption has 

 been reported in various chronic anemias (72) and 

 in pernicious anemia (154), diseases in which ar- 

 terial Oxygen content rather than tension is de- 

 creased. Successful trealinenl of the pernicious anemia 

 onl\ partially restored the normal metabolic rate, 

 evidence either of an irreversible effed of a prolonged 

 oxygen deficiency in the brain or of some other 

 intracellular effect of the disease quite independent 

 of the anemia. Changes in menial function closely 

 paralleled the changes in cerebral oxygen consump- 

 tion, ll iniisi be pointed OUt, however, that the re- 

 duction in cerebral oxygen consumption observed in 

 the anemi.is may be the result of a methodological 

 error in the application of the nitrous oxide 

 technique the use of .1 brain-blood nitrous oxide 

 1 mi in 1 1 1 H nil 1 uncorrected for the anemia (96). 



Prolonged cerebral anoxia leads to irreversible 

 intracellular metabolic changes. In a case of strangu- 

 lation estimated to have lasted to min., studies done 5 



davs later while the patient was still in coma revealed 

 a lowered oxygen utilization by the brain despite a 

 normal cerebral blood flow and oxygen supply (39). 

 As for the effect of cerebral oxygen deficiency on 

 the intermediary metabolism of the brain, studies in 

 animals have demonstrated changes compatible with 

 an increased rate of glycolysis and a depletion of 

 energy-rich phosphate compounds. In clogs, the 

 inhalation of 5 to 10 per cent oxygen results in rela- 

 tively little change in glycogen or glucose contents, 

 a marked increase in lactic acid and a lesser one in 

 inorganic phosphate concentrations, and a fall in 

 the phosphocreatine level of the brain (70). Little 

 change in the ATP level was observed, probably 

 because of its maintenance by the creatine phosphate 

 still present. In cats ( in-,) and in rats (2) similar effects 

 were observed following the administration of cyanide 

 except that the ATP level was also markedly de- 

 creased. 



glucose deficiency. A deficiency of the other es- 

 sential nutrient, glucose, is also associated with 

 disturbances of mental function, which have been 

 described in a previous part of this chapter. The 

 metabolic aspects of coma resulting from administra- 

 tion of insulin, however, deserve further consideration. 

 In the studies of Kety and co-workers (103), at 

 arterial glucose levels of 8 mg per cent, cerebral 

 oxygen consumption fell to 1.9 ml per too gm per 

 min. and cerebral glucose utilization was negligible. 

 Accordingly, other substances must have been 

 oxidized. Since the R.Q. remained approximately 

 unity, however, these substances must have been 

 predominantly carbohydrate, derived probably from 

 the carbohydrate stores within the brain which have 

 been found to be depleted in insulin hypoglycemia 

 (go, 135). Since the total stores of glycogen and 

 glucose within the human brain have been estimated 

 to be equivalent to approximately 2 gm of glucose 

 (90, 92), at the low rate of cerebral oxygen consump- 

 tion in insulin coma these stores would be depleted in 

 about 90 min. Indeed, this is about the lime limit 

 beyond which insulin coma results in irreversible 

 changes in the brain (92), a development which 

 might, perhaps, lie attributed to irreversible intra- 

 cellular damage resulting from (he oxidation of 

 Structural and enzymatic components of the brain 

 following the exhaustion of carbohydrate stores. In 

 such cases, coma and ,1 remarkably low rate of 

 cerebral oxygen consumption persist until death (38). 

 Glucose can no longer reverse ihis picture even when 

 ii is administered in amounts sufficient 10 produce 



