SOME IMPORTANT CLINICAL DETAILS R E L A T E D TO ANEMIA.

The anemia of the partially gastrectomized patients usually develops so gradually that they do not react until the condition is well advanced. It thus often happens that the patients are surprised to hear that they are anemic, and i t is not until the disease is cured that they realize how sick they have been. This typical feature, also pointed out by HOLST LARSEN (1934) is in accordance with the fact that the anemia is the result of a protracted, but not severe loss of iron which is not compensated by sufficiently rapid resorbtion of alimentary iron.

The symptoms of the anemia are the same as the usual ones, mostly inertia, weariness, and poor appetite. In several cases there were severe headaches, and in one case (case 218) the headaches were so persistent that they led to abuse of analgetics. The general symptoms and headache disappear when the anemia is cured.

Dyspeptic symptoms were observed in both non-anemic and anemic operated patients. Of 115 non-anemic, 41 complained of various kinds of dyspepsia, of 31 anemic 14 had dyspepsia. The patients with anemia usually said the dyspepsia was improved after the anemia was cured. It is possible that this has some con- nection with the injury to the epithelium which is due to iron deficiency. The epithelium grows stronger when the iron deficiency is abolished.

Many of the operated patients were thin and several complained that they were unable to gain weight in spite of good appetite and adequate nourishment.

Twelve of the anemic patients had definite sideropenic epithelial symptoms. Seven others exhibited slighter and more doubtful symptoms such as split finger- nails, smooth tongue, a tendency to rhagades. The most common and most reliable symptom was alteration of the nails in the form of koilonychia. Severe sideropenic epithelial symptoms were observed in 4 women (cases 250, 256, 223 and 311). All of them had considerable difficulty in swallowing, and a t the same time nail alterations, rhagades and sore tongue.

Slight epithelial symptoms were also recorded in non-anemic operated patients, in 15 of 115 examined, but they exhibited no manifest objective symptoms.

l o o much significance cannot be ascribed to information on cracks a t the corners of the mouth and brittle nails, as these phenomena are most certainly also found in other conditions than iron deficiency.

There were no indications of severe organic nervous diseases in any of the operated patients. The examination has probably not been sufficiently thorough in this respect to exclude the possibility of slight alterations. It is a t least certain that there were no pronounced symptoms of funicular sclerosis. I t is my opinion that it is incorrect to emphasize paresthesia-like sensations in this respect. Such information is frequently obtained from both sick and healthy individuals. Characteristically, some of the controls also had these complaints when they were questioned specifically.

WARBURG and JORGENSEN (1928) have pointed out that a number of patients with achylia have neurasthenic symptoms, bordering on psychoses, and they relate this to the finding of megalocytosis in the blood as a kind of ,forme fruste)) of pernicious anemia. The symptoms were overcome with the administration of hydrochloric acid and liver extracts.

No megalocytosis could be demonstrated in our patients, but there is no doubt that some of the partially gastrectomized exhibit symptoms which may be best characterized as neurasthenic. The symptoms were observed in both anemic and non-anemic, and iron therapy seemed to have little effect on them. However neurasthcnic symptoms are common in ulcer cases also before operation, and i t is perhaps more than doubtful that they have any connection with achylia or anemia in partially gastrectomized cases.

One significant point was discovered as regards the anemic women with severe menstrual bleeding. I t has been frequently claimed, inter al. by VAUGHAN (1936) that the bleeding becomes normal when the achylic anemia of such women is cured. This is not true in our operated material where the reverse was more often the case. Cases 256 and 257 said that there was no difference in the intensit or frequency of the bleeding before and after treatment. Case 250 had the impression that there may have been slightly less bleeding during the first period of therapy, but that i t was just as strong again after the anemia was cured, and case 283 said that she had had anemia the year hefore the examination and that she bled more profusely after the anemia was cured.

Of considerable interest are the findings made in the children of anemic, sidero- penic mothers. As already mentioned, I have encountered only 3 children in this category. Case 256 had given birth to 2 children after the operation. When the mother was examined the oldest was 3 years, the youngest 9 months. The oldest child had to have iron which was perscribed by a physician when i t was one year old. It was said that the child was anemic because of a diet which consisted mostly of milk. I examined the youngest child personally when it was one year old. I t was very pale and flabby. The Hgb.yo was 57, r.b.c. 4.8 mill./cmm. (color index 0.59). The child was treated with iron, 75 mg. bivalent iron 3 times a day. In 3 weeks

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the Hgb. increased to 87%, the child was totally changed, grew active and lively and developed a good appetite.

Case 257 had a child about 2 years after the operation. At the final examination the patient brought her 1% year old child with her as requested. It was very pale. The fingernails were split and flat. Hgb.yo was 64. This child was also treated with iron, and according to information received improved considerably as a resu It.

I have not been able to find any special investigations of the children of anemic, iron deficient mothers, but I have been told that pediatrists do not expect such children to be born with poor iron reserves. However i t seems highly probable that the 3 children described here were anemic because of insufficient supply of iron in utero, due to the mothers’ iron deficiency.

It has not been possible to overlook the further fate of these children if they had not been treated with iron. Is i t not reasonable that an iron deficiency from birth might have marked these individuals for the rest of their lives? We know how sensitive the epithelium is to iron deficiency. In the light of the arguments put forth earlier in this investigation, i t is not improbable that the resorbing cells in the intestinal mucosa have a reduced capacity to resorb iron for the very reason that there is an iron deficiency in the organism. Have we perhaps in this a possibility of explaining the term ))hereditary hypochromic anemiau (LUNDHOLM, 1939) and perhaps also that mysterious ailment, chlorosis?

All considerations of the relation between chlorosis and other hypochrome anemias, including achylic anemia, have come to an end since this disease has disappeared as a clinical phenomenon, although hypochrome anemias are still occasionally observed in young girls. I have tried to regard this problem in the light of our present knowledge of modern, rational iron therapy. HADEN (1938) has given a review of the history of iron therapy in a very interesting paper. I t appears that there was no really rational iron therapy before Blaud’s time (1831). Blaud’s instructions were followed by a number of clinicians all over the world, but i t is not until almost recent times that i t has been possible to reach everyone with treatment of iron deficiency. This has been made possible only since the relatively recent increase in the number of physicians and the frequency with which they are consulted, and since medical care has been extended through social institutions. However there was a turning point in the view of the value of iron around 1890, initiated by Bunge’s dogmatic postulation that iron in metallic form was only converted to sulphide and excreted, whereby only organic iron compounds could have any therapeutic value. Well-known clinicians such as Quincke and v. Noorden claimed moreover that i t was never necessary to administer more than 100 mg. iron daily to patients with hypochromic anemia. This standpoint was maintained for about 30 years and its greatest significance was in the form of unsuccessful iron therapy. The change to large doses of metallic iron came around 1920 with Lichtenstein and Meulengracht’s investigation, and

since that time there has never been any doubt that inorganic iron compounds in large doses are the rational therapeutic method.

It seems to me that chlorosis has disappeared with the instigation of rational iron therapy. Children are now seldom b rn with inadequate iron reserves, and no longer develop an early iron deficiency which again leads to faulty iron resorbtion. Consequently they do not develop chlorosis during adolescence when rapid development requires increased iron resorbtion and menstruation further increases the loss of iron.

This line of thought can be followed still further. Is it possible that the iron deficiency which we still see rather frequently in women towards the end of the menstruating age is an expression of the same process as chlorosis? If the effect of our iron therapy is only felative, i t may well be that anemia now develops later than i t used to, perhaps particularly under the influence of the constant loss of iron which takes place through menstruation, which, moreover, often increases toward menopause. And finally there is no reason why i t might not be assumed that the epithelium of the stomach is gradually affected so.much by the constant iron deficiency in the organism that an achylia develops on this basis.

All of this is naturally only theoretical, difficult to prove and based on only a few observations on iron deficiency anemic mothers who have been partially gastrectomized. But there is, in any case, every reason to bear these possibilities in mind, and to give iron deficient, anemic, expectant mothers rational treatment as well as their children, the latter as early as possible.

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