Some Aspects of the Pathology of Anaemia--I

By 1932 Castle's hypothesis that pernicious anaemia was due to the absence of an intrinsic factor in the gastric juice which reacted with an extrinsic factor in the diet to produce the haemopoietic factor had been generally accepted. There were still, however, certain reservations. There was doubt whether complete loss of the stomach in man inevitably led to pernicious anaemia, for it did not do so in animals, and at that time there were few patients whose life had been prolonged more than a year or so after total gastrectomy. As the number of survivors has grown we have learned that pernicious anaemia always develops if the patient lives long enough, though it may take several years for the body to exhaust its stores of vitamin B12 (Paulson and Harvey, 1954). Another difficulty was that achlorhydria was thought to be quite common, 20 to 30% in the later age-groups after a single body-dose of histamine (Polland, 1933). Estimation of intrinsic factor by the Castle test was a long and arduous procedure, not without danger to the patients used as test subjects, so that no large series of individuals with achlorhydria but without pernicious anaemia was studied. Since the introduction of the augmented histamine test and similar methods of giving a maximal stimulus to the parietal cells we know that true achlorhydria occurs much less often than used to be believed and is always evidence of disease of the stomach (Witts, 1959). Of the patients with complete achlorhydria a moiety will also have lost their ability to secrete intrinsic factor (Callender, Retief, and Witts, 1960). The total number of such cases seems relatively large in relation to the prevalence of overt pernicious anaemia (Witts, 1960). Nevertheless, it is doubtful whether we need invoke any other factor than the exhaustion of the tissue reserves of vitamin B12 to explain the transition from larval to overt pernicious anaemia.