Acid–base physiology: new concepts

The traditional approach to acid–base physiology is based on the Henderson–Hasselbalch equation which is derived from the ${\text{CO}}_2/{{\text{HCO}}_3}^{?}$ buffer system. However, it is becoming increasingly recognized that this is an incomplete analysis as it focuses on only one of the six reactions involving H⁺ and can lead to the incorrect assumption that CO₂ and ${{\text{HCO}}_3}^{?}$ are independently adjusted factors that ultimately determine pH. In 1983, Stewart, a Canadian physiologist, proposed that a fuller understanding of acid–base physiology required consideration of biological fluids as a complex dynamic system, taking into account the interactions of all the chemical species involved. He showed that the true independent variables controlling the pH of any given fluid compartment are: the difference in the concentration of ‘strong ions’; the total concentration of ‘weak acid’; and the PCO₂. Importantly, H⁺ and ${{\text{HCO}}_3}^{?}$ are dependent variables and it is incorrect to think of them as being specifically regulated to manipulate pH. This review will discuss the importance of pH homeostasis and highlight the implications of the Stewart approach in our understanding of acid–base control mechanisms and disorders. In particular, the true mechanisms by which the kidney regulates plasma pH will be discussed, emphasizing key misconceptions that have been propagated as a result of the traditional approach.     

Acid–base physiology: new concepts

The traditional approach to acid–base physiology is based on the Henderson–Hasselbalch equation which is derived from the CO₂/HCO₃⁻${\text{CO}}_2/{{\text{HCO}}_3}^{-}$ buffer system. However, it is becoming increasingly recognized that this is an incomplete analysis as it focuses on only one of the six reactions involving H⁺ and can lead to the incorrect assumption that CO₂ and HCO₃⁻${{\text{HCO}}_3}^{-}$ are independently adjusted factors that ultimately determine pH. In 1983, Stewart, a Canadian physiologist, proposed that a fuller understanding of acid–base physiology required consideration of biological fluids as a complex dynamic system, taking into account the interactions of all the chemical species involved. He showed that the true independent variables controlling the pH of any given fluid compartment are: the difference in the concentration of ‘strong ions’, the total concentration of ‘weak acid’, and the PCO₂. Importantly, H⁺ and HCO₃⁻${{\text{HCO}}_3}^{-}$ are dependent variables and it is incorrect to think of them as being specifically regulated to manipulate pH. This review will discuss the importance of pH homeostasis and highlight the implications of the Stewart approach in our understanding of acid–base control mechanisms and disorders. In particular, the true mechanisms by which the kidney regulates plasma pH will be discussed, emphasizing key misconceptions that have been propagated as a result of the traditional approach.     

5-hydroxytryptophan-induced myoclonus: increased sensitivity to serotonin after intracranial 5,7-dihydroxytryptamine in the adult rat.

Systemic administration of the serotonin precursor, 5-hydroxytryptophan, produced tremor and myoclonus in rats previously treated with intracisternal injections of 5,7-dihydroxytryptamine and systemic desmethylimipramine, but not in their controls. The behavioural syndrome developed to a maximum at 10–14 days, and persisted at least 16 weeks following intracisternal 5,7-dihydroxytryptamine. The myoclonic syndrome was potentiated by pargyline, but was blocked by d-lysergic acid diethylamide, 2-bromolysergic acid diethylamide, methysergide, and centrally active high doses of the decarboxylase inhibitor, Ro4-4602. Drugs that increase or decrease the effects of other proposed central nervous system neurotransmitters (dopamine, norepinephrine, acetylcholine, and γ-aminobutyric acid) neither reproduced the syndrome nor altered the myoclonus following 5-hydroxytryptophan. Thus, myoclonus induced by 5-hydroxytryptophan following treatment with 5,7-dihydroxytryptamine + desmethylimipramine appears to be specifically related to central indoleamine neurones and may reflect pre- or postsynaptically mediated supersensitivity to serotonin. This animal behavioural syndrome may be relevant to some forms of clinical myoclonus, and should be useful in testing agents that act as agonists or antagonists at serotonin receptors in the central nervous system.     

Psychiatric interface with neurology: Conflicts and cooperation

The recent interest in biologically oriented psychiatry has opened up new opportunities for collaboration between psychiatry and neurology. Traditionally neurologists emphasized neuronal pathways and lateralizing signs, while psychiatrists' main interest was feeling states and emotions. Increasingly, both specialties are becoming aware of the complexity of the nervous system and the frequency with which neuronal disturbances and psychological conflict interact and influence treatment and outcome. The most important factor in facilitating an increased number of consultations and generating research protocols involves achieving a certain mutuality and complementary role between two disciplines. Traditionally there has been a fair amount of antagonism, primarily because of each specialty's insistence that its vantage point of view was correct. The consultation-liaison psychiatrist is in the ideal position to bring about a rapprochement. To achieve this, it is paramount that the psychiatrist understand and be conversant in the neurologist's language.     

Pugh's nail fixation versus Thompson's prosthesis for displaced subcapital fractures of the femur

A retrospective study of 100 fresh displaced subcapital fractures of the femoral neck is reported, comparing the results of treating 50 by primary Thompson's prostheses with 50 of those treated by internal fixation with Pugh's nail and plate. Up to 3 months, the mortality following Thompson's prosthesis was higher than that following internal fixation but was comparable at 1 year.In general the results were comparable at 1 year but the failure rate in that time was higher following internal fixation, leading to a much higher number of second operations.