A clinical study of achlorhydria

T H E IRISH J O U R N A L MEDICA L SCIENCE THE OFFICIAL JOURNAL OF THE ROYAL ACADEMY OF MEDICINE IN IRELAND

OF

SIXTH SERIES. No. ?5. MARCH, 1932.

A CLINICAL STUDY OF ACHLORHYDRIA. By HF~RY MOORE.

(From the Mater Misericordi~ Hospital, Dublin.)

F OR more than ten years I have been interested clinically in achlorhydria, and about five years ago my interest in this connection became acute when some peculiar cases 0s

anmmia in middle-aged women presented themselves. Th~ anaemia in these patients appeared at first sight to be perniciou~ in type, inasmuch as there was atrophy of the lingual papill~ associated with superficial glossitis and achlorhydria, and tho

pat ients had a sallow, subicteroid or pale complexion. The blood examination, however, showed an anaemia with a colour index well below unity, megalocytosis was absent, and although there were anisocytosis and poikilocytosis, the average size of the erythrocytes was not greater than normal; the anmmia, therefore, was not Addisonian in type. As the standard textbooks gave no information about this syndrome, and as a superficial search of the journals furnished but little, it was evident that we were dealing with a form of anaemia not generally recoguised. During the following years, namely, from January 1st, 1927, to June 30th, 1931, we endeavoured to collect, and when possible to study, cases of this form of anmmia, that is, cases of non-megalocytic anaemia with a low colour index and aehlorhydria; we sueceedod in collecting 33 such eases in which the h~raoglobin content of the blood was under 70 per cent. Furthermore, during the same period, we made fractional test-meal analyses on as many other patients as was possible, with the idea of obtaining some information relative to the incidence of achlorhydria in other diseases. Naturally, we were unable to have test-meals done on all cases entering the wards, and at first we concentrated on eases which symptomatically might be likely to have achlorhydria. The in- eidence of achlorhydria in some of the groups (e.g., diabetes mellitus) may be somewhat higher in this study than is actually the fact, because in the earlier part of the work only such cases of the group as showed symptoms or signs suggestive of achlorhydria were tested, whereas, after we realised from our growing experience that absence of hydrochloric acid from the gastric secretion was a rather common finding in the disease, then all eases of that group entering the wards were tested by fractional test-meal as a routine. For this reason, and because the number of eases tested is too small, the incidence figures of the frequency of achlorhydria in this study cannot be taken as having statistical

98 IRISH JOURNAL OF MEDICAL SCIENCE

value; but, at the same time, we believe that they give some in- dication of the frequency of aehlorhydria in certain conditions.

Methods.--The three-hour fractional test-meal technique, with a Ryle tube and a thin gruel, was used; if there was any doubt about the presence of achlorhydria, or if there was much mucus present in the majority of the specimens, the stomach was thoroughly Washed out, as recommended by Hurst, and the test-meal repeated. In certain cases the fasting gastric juice was aspirated and the test-meal was repeated after the subcutaneous injection of 0.5 rag. of histamine, in the form of acid phosphate, which is known to be a powerful stimulant of gastric secretion a, or the fasting stomach was twice evacuated 20 and 50 minutes after histamine injection; wherever this method was used it is mentioned in the tables. We have made no attempt to test for pepsin in the gastric contents. The fasting blood sugar was estimated by the Folin-Wu method and the basal metabolic rate was determined by means of ~he Roth-Benedict apparatus. H~emoglobin was estimated by a checked Sahli test and a certified Biirker chamber was used for the blood-counts.

Table I gives a general summary of our results; it shows that out of 47 cases of so-called " secondary," " hypochromic," or non-megalocytie ansemia, 33, or 70 per cent., had achlorhydria. This particular form of anaemia, therefore, is probably one of the commonest type of anaemia encountered; it is certainly surprising that so little attention had been paid to it in the literature and that it was so seldom recognised in practice. T h e table also shows that out of 83 cases of diabetes mellitus, 33, or over 39 per cent., had achlorhydria, and out of 47 cases of hyperthyroidism, '37, or over 78 per cent., had achlorhydria. There were 100 gastro-intestinal eases and 74 miscellaneous cases with achlorhydrla. Out of a total of 1,228 patients tested by the fractional test-meal method in 3�89 years, 272, or 22 per cent., had achlorhydria, as judged by this technique.

Achlorhydria is not unlrnown in otherwise apparently healthy individuals; Bennett and Ryle* found an incidence of 4 per cent. with the fractional test-meal, and Baird, Campbell and Hearn~ found an incidence of 3.5 per cent. with the same method in. apparently normal persons. Connor B has shown that the frequency of achlorhydria in patients increases as age advances; in patients of from 30-39 years of age there was an incidence of 10.5 per cent., while in those of 60 to 67 years of age it was 28 per cent. ; in 5,000 patients suffering from a variety of diseases Connor found achlorhydria to be present in 15.2 per cent. by the fractional method. Fabel ~i also found that achlorhydria in- creased in frequency with advancing age. I t may be of interest to note here that pylorospasm, as noted by x-ray examination, and comparatively rapid emptying of the stomach, as judged by the time required for the gastric evacuation of starch, were frequer.t findings amongst our cases of achlorhydria (provided that organic obstruction or marked-gastric hypotonia was absent).

A CLINICAL STUDY OF ACHLORHYDRIA 99

The Ancemia (Table 2).--Of the 33 cases of non-megalocytic anaemia of unknown origin with achlorhydria there were 27 females and 6 males. The anaemia was chronic in all, and in some had Iasted for several years. Weakness, palpitation and breath- lessness on exertion were common symptoms. Many of the patients complained of digestive disturbances, such as flatulence and epigastric discomfort after food, diarrhoea, vomiting after food or loss of appetite. The complexion was usually sallow, but sometimes pale. A frequent finding, present to some degree in 19 of the 33 cases, was atrophic superficial glossitis, very similar to the form so frequently found in pernicious amemia, the tongue often being too red, and the papillae having in many cases com- pletely disappeared from the dorsum; in some, this condition was patchy in distribution or more advanced in some areas of the dorsum linguae than in others; furrowing of the tongue was even more common than glossitis; some degree of regeneration of the atrophic papilhe was occasionally observed after successful treatment, and frequently the redness and furrowing beeafiae less. Par~esthesia and signs suggesting subacute combined degeneration of the spinal cord were not observed, but menstrual irregularity was not uncommon. The average number of erythrocytes wa~ about 3,700,000 per c.m., and the average h~emoglobin content of the blood was 50 per cent. before treatment; the lowest red cell count was 1,920,000 per c.m. and the lowest h~emoglobin measure- ment was 15 per cent., both in the same patient (Case No. 19). In some patients the red cell count was about normal, but a considerable h~emoglobin deficiency existed. The average colour index before treatment was 0.66 (lowest, 0.32, and highest, 0.95). The average colour index after successful treatment in twenty cases was 0.86 (lowest, 0.61, and highest, 1.04). The average leucocyte count before treatment (excluding Case No. 17 where there was a polymorphonuclear leucocytesis from severe oral sepsis, and Case No. 32 where there was a thyroid abscess with a leucocytosis) was 5,200; after successful treatment in 19 cases it was 7,022 as against 5,400 on admission. The differential leucocyte count was normal in all, except in Cases No. 17 and 32 which showed a polymorphonuclear leucocytosis. The degree of anisocytosis and poikilocytosis was usually in proportion to the severity of the anaemia. The average diameter of the red cells was never greater than normal. Blood bilirubin, the platelet ~ount and the reti- culocyte c.ount, before treatment, were normal in ell tested (ten). No cases are included in the present series who were under 15 or over 70 years of age or unless the blood h~emoglobin was under 70 per cent. In the series, there was one case (No. 29) of the so-called Plummer-Vinson syndrome? and the spleen was enlarged in only two (Nos. 29 and 33). This variety of anaemia occurred in two eases of diabetes mellitus and in three cases of hyperthyroidism, all five of which had achlorhydria (one of the latter is not included in Table 2). In all cases a h~emorrhagic cause was carefully excluded.


Twenty-three cases submitted themselves to treatment for a period sufficiently long to show an excellent response to oral iron therapy; with the exception of one case, No. 32, who died of infection, the blood values h~moglobin content, erythrocyte and leucocyte counts-~were restored to normal, or considerably improved, while there was at the same time great symptomatic improvement. Iron by mouth gave good results in treatment, as shown by the table. At first we used citrate of iron by mouth in treatment and found that 60 grains per day were necessary to get a good result in three to five months; later we found that Blauds' mass in doses of 30 to 45 grains per day gave a much quicker response, the period of time necessary for effective treatment being in some eases reduced to from 4 to 6 weeks. Thirteen of the successfully treated eases were tested for the presence of hydrochloric acid in the stomach (fractional test-meal) after the anemia had responded to treatment and the acid was then found to be present in only three, namely, the Plummer-Vinson case (No. 29), which showed a normal curve .of gastric HC1 without histamin, one case (No. 2), which showed traces without histamin, and Case No. 17, which had no gastric HC1 with the ordinary technique, but showed it two years after treatment with histamine. Seven cases which showed aehlorhydria with the ordinary fractional test-meal technique after successful treatment of the anemia also had achlorhydria after histamin injection. These findings would indicate that the anemia was not the cause, but more probably, in part at least, the result of the achlorhydria. The administration of 60 minims of dilute hydrochloric acid (B.P.) by mouth with pepsin, thrice daily, after food, did not seem to be of any special value in restoring the blood to normal, but it was of undoubted value in relieving the frequently associated gastro- intestinal symptoms. Liver extract for pernicious ansamia and desiccated stomach proved useless. The administration of whole cooked liver by mouth gave doubtful results, but I obtained the impression that its use was of some value as an adjunct to iron; however, I am not prepared to be definite on this point. Neither can I be dog- matic on the best form of maintenance treatment once the anemia has disappeared; some patients have kept well for a year, or even more, on small doses of iron, some on moderate doses of hydrochloric acid, and at least one (No. 17) on no special form of medication; it is interesting to note that two years after successful treatment this case (No. 17) showed HC1 in the fractional test. meal after histamin injection, but none on the ordinary technique (no histamin) before treatment. I t is worth mentioning that we have had a female patient with true achlorhydria under frequent observation since early in 1928 who, in September, 1931, developed for the first time glossitis and non-megalocytie anemia ~f a mild type, although she had been continuously taking 40 to 60 minims of dilute hydrochloric acid with pepsin by mouth, thrice daily, after food; she is not included under the heading of


ansemia in this paper, for the blood changes developed after this study had ended. In this case, the taking of the acid as a prophylactic measure in these doses did not prevent the ultimate development of the anaemia. It would seem probable t ha t both iron and hydrochloric acid would each have its own place in maintenance treatment, iron b e i n g probably by far the more important. The achlorhydria in the majority of these 33 cases was probably a true and not an apparent achflor- hydria, for suitable precautions were used in all the fractional test-meals; for example, several test-meals were done on most o f the patients, the stomach in many cases being washed out beforehand, but the histamin stimulation method was unfor- tunately only used in a minority (eight) of the patients before treatment.

As regards the aetiology of this non-megalocytic anaemia, one is at once impressed by the fact that it is commonest in women from the ages of 20 to 50 years, although examples of it were encountered in male patients from the ages of 15 to 59 years. I t would appear that achlorhydria is the most important single aetiological factor, although probably there are others. In this connection, one might note that recently Mettier and Minot t~ have shown ex- perimentally that " iron is more potent for blood production in secondary anaemia when absorbed from an acid than an alkaline medium within the gastro-intestinal t ract ," and they suggest that " anaemia can result from failure over a prolonged period in the adjustment of the Contents of the upper intestinal tract to a suitable pH for iron utilisation, e.g., aehylia gastriea."

We have seen 12 eases of secondary anaemia of unknown origin with HC1 present in the stomach Contents, and 31 eases of anaemia referable to a definite cause (pernicious anaemia excluded), as against 33 eases of non-megalocytie anaemia with aehlorhydrla, during the period in which the present study was carried out (Table 3). These figures give an idea of the relative importance and prevalence of this non-megaiocytie anaemia with aehlorhydria.

To summarise, one may say that one of the commonest forms of " secondary " anaemia, especially in females, is this non-megaloeytic form which is associated with aehlorhydria, that it is probably due to deficient formation of h~emoglobin, that it is not h~emolytie or h~emorrhagic in origin, and that its appropriate treatment with iron gives eminently satisfactory results.

Relevant details of these 33 eases o f non-megalocytic anaemia of unknown origin with aehlorhydria are shown in Table 2. Certain of these eases require comment. Case No. 3 had Graves' disease and is Case No. 9 of Table 5 under the heading of hyperthyroidism; the anaemia was refractory to treatment with hydr0. ehlorie acid alone, but readily improved on iron being given by mouth; the hyperthyroidism showed a satisfactory result from non-operative treatment; she was still in good health three and a half years after her first visit.

Case No. 6 had a relapse some months after ceasing treatment,


but again the anmmia yielded to hydrochloric acid and iron by mouth.

Case No. 7 had a relapse on a maintenance treatment of hydrochloric acid by mouth alone, but again a good result was obtained on iron.

In Case No. 16 treatment was refused at first examination. We asked the patient to return four years later, when the anaemia and achlorhydria were found to be present to almost the same degree; thirty grains of Blauds' mass per day by mouth caused the h~emoglobin to rise from 52 to 76 per cent. in 67 days, and it rose to 80 per cent. later. This case showed a mild degree of infantilism.

Case No. 17 had secondary (non-thrombocytopcenic purpura hmmorrhagica and severe oral seps is ; - there was a polymorphonuclear leucocytesis (10,000 per c.m.) The treatment consisted of clearing up the oral sepsis by mouth hygiene, dental extraction and giving hydrochloric acid and iron by mou~th; both the anmmia and purpura readily responded to treatment. HC1 was absent from the stomach contents two years later on the ordinary technique, but was present after histamin; neither the anemia nor the purpura reappeared in this period, although the patient was on no special treatment for the final year. Possibly the oral sepsis was one important factor in causing the anaemia.

Case No. 24 is of special interest. She had been under treatment with diet and insulin for diabetes mellitus for seven years when symptoms suggestive of achlorhydria caused us to make a test-meal examination, which showed achlorhydria. Hydrochloric acid in 60 minim doses thrice daily with pepsin a f t e r food relieved the gastro-intestinal symptoms, but after a year this treatment was carried out only irregularly. Two years after the achlorhydria was discovered, the anaemia developed, and this readily yielded to iron in the form of Blaud's mass with HC1 and liver, the h~emoglobin rising from 50 to 90 per cent. in 44 days. (Case 9, Table 4.)

Case No. 28 also had diabetes. Anaemia developed two and a half years after the treatment with diet and insulin was started; she was then found to have achlorhydria. The anaemia readily yielded to treatment with iron and HC1. There was no relapse in nine months on treatment with HC1 alone, in addition to anti- diabetic measures (Case 32, Table 4).

Case No. 29 was the only one which exhibited the so-called Plummer-Vinson syndrome, originally described by Kelly. 11 The cesophagospasm in this case was in the lower third of the oesophagus. Atrophic superficial glossitis was present, the tongue being smooth, red and furrowed; there were cracks at the angles of the mouth, and the spleen was enlarged. The patient was edentulous and had eaten no meat for months. Six days after cesophageal dilation by cesophagoscope by Dr. Dempsey she was able to swallow normally, and the test-meal (without histamin)

A C L I N I C A L S T U D Y OF A C H L O R H Y D R I A 103

showed achlorhydria. With t rea tment by HC1, iron and a normal diet ( including meat) the anaemia quickly disappeared, the spleen a f t e r three weeks was no longer palpable, the tongue became almost normal and the cracks at the angles of the mouth disappeared. When t h e blood count was normal the stomach secretions were re-tested, and HC1 was found to be present in normal amount without the use of histamin. I t is interesting to speculate as to whether a similar result would have been obtained if the HC1 and iron had been omitted, and as to whether the achlorhydria was secondary.

Case 32 showed the r a re combination of hyper thyroidism, acute thyroid abscess, achlorhydria and anaemia. The anaemia readi ly yielded to t rea tment by HC1 and iron a f te r the thyroid abscess h a d been drained by Mr. P. J . Smyth, but the hyper thyroidism persisted unti l a t empora ry remission was obtained through iodine by mouth (Case 36, Table 5).

Case No. 33 proved re f rac tory to t rea tment by HC1 and iron (B laud ' s mass, 45 grains per day b y m o u t h ) for severa l weeks; she then deve loped acute r ight-sided parot i t is with a subcutaneous abscess behind the r ight ea r ; notwithstanding surgical dra inage she died and, in m y absence, my house physician, Dr. Molloy, removed the l iver and spleen and some tibial bone-marrow; he found the gastro-intestinal t rac t maeroseopically normal ; these specimens were examined by Dr. W. R. O 'Far re l l , whose repor t was as follows : -

Liver. The liver weighs 1,062 gins. I t is of tlrm consistency, a n d t h e capsule is slightly thickened. The portal areas are conspicuous and the branches of the hepatic vein are dilated- There is some (but notmarked) round-celled infiltration in the neighbourhood of the portal areas, but no fibrosis (verified by van Gieson's stain). There is slight cloudy swelling of the liver cells~ which also show a patchy fatty degeneration and infiltration ; this is confined for the most part to the outer-third zone of the lobule, but in places whole lobulas are affected.

There is some, but not a large amount of h~emceiderin pigment in the Kiipffer ceils towards the outer zone cf the lobules.

Spleen.--The spleen weighs 343 gins. (which is about twice the normal size}. The consistency is firm, the margins are rounded and the notches a r e salient. Some fine fragile adhesions are pre~nt on the convex surface. The capsule is thickened. There is no increase of fibrous tissue of the parenchyma (verified by van Gieson's stain). The Malpighian bodies are normal; there is no congestion or packing of the spleen pulp.

A few eosinophile cells are to be seen, but not in any large numbers. ~rery little h~emosiderin pigment is present. The condition is a pure hyperplasia without any qualitative alteration in structure.

Bone marrow #ore middle of tibia. The bone marrow is of the erythro- blastic type, and large numbers of red blood corpuscle~ are present. Normoblasts are present, but not in sufficient numbers to constitute any striking feature. Myeolytes and lymphoid cells are in evidence. Megalo- blast~ are not in evidence.

I t should be noted tha t the infection in this ease, last ing over a week, may have modified to some extent the p r i m a r y post-mortem findings.

In March, 1930, when the present s tudy was drawing to a close, the first comprehensive account of this par t icular fo rm of anaemia in Bri t ish l i tera ture was given by Wittsi~; our own results, up to date, were reported to the Royal Academy of Medicine in I re land 1.

104 IRISH JOURNAL OF l~IEDICAL SCIENCE

on March 14th 1930, and summarised in the Brit ish M~dicaZ Journal ts. As Witts is, ,s and Davies ~e have gone fully into the literature it is unnecessary here to do more than to point out that Faber ~T described the disease in 1913, but his description did not seem anywhere to get the attention which we now know that it deserved. As far as our cases are concerned, the clinical picture seems to resemble closely that described by Witts, except that while he notes that koilonychia was occasionally seen, we have never seen it in any of our cases, and that he encountered splena- megaly more frequently than we did.

Reference might here be made to terminology. Up to about eighteen months ago w e frequently referred, in clinical lectures, to this disease a s " achlorhydric anEemia," but we believe that we have recently encountered some samples of it with traces of HC1 present in the stomach contents, and this makes it doubtful whether such a term should be employed in its designation; con- sequently, for the present, we prefer the name, although cumber- some, of " non-megalocytic anaemia with achlorhydria " in order to distinguish it from pernicious anaemia, which is macrocytie and which is, except in very rare instances, a~ociated with achlorhydria (the writer has only seen one ease of pernicious amemia without achlorhydria). Again, we prefer the term non-megalocytic, rather than microcytic, as used by Witts, for in our series, while none showed macrocytosis, some cases did not show microcytosis. Probably the only real primary anaemia is some form of aplastic amemia; a s knowledge grows, most forms of anemia will probably be shown to be " secondary." For example, it is now believed that pernicioum anaemia is secondary to defective formation by the stomach, or defective absorption, of an erythro- poietie substance.

Achlarhy&da i~ Diab~te~ M~Ilitus.

Amongst 83 eases of diabetes mellitu8 achlorhydria was found in 33, or 39.7 per cent., 6 eases had traces of gastric HC1, 10 had hypochlorhydria, 30 had the acid present in normal amounts, and 4 had hyperehlorhydria. Histamin was not used in these eases except in a few odd instances; whenever there was acidosis the test-meal examination was not made until several days after the ketosis had disappeared as a consequence of treatment. The results are shown in Table 4, where the level of the fasting blood sugar is given and where any complicating conditions are given under the heading " Remarks " ; of these patients, 44 were males and 39 females; achlorhydria was present in 13 males and 20 females. Probably the incidence of achlorhydria in these cases is somewhat high for the reason already mentioned, but it is clear that the condition is a frequent finding in diabetes mellitus. Curiously enough, comparatively few diabetic patients with achlorhydria complained of the gastro-intestinal disturbances which ale frequently associated with absence of the gastric acid. Super- fieial gl~ssitis was also rare amongst them, but the two patients


(Nos. 24 and 28, Table 2, and 9 and 32, Table 4) with aehlorhydria, who developed anaemia, both had superficial glossitis, flatulence and diarrhoea. The rarity of gastro-intestinal symptoms and glossitis ~ amongst diabetics was probably responsible for the fact that we did not become aware that achlorhydria was fairly common in diabetes until the present study was well under way.

A search of the literature showed that others have noted a fairly high incidence of achlorhydria in diabetes mellitus: Joslin ts gives a figure of 27.3 per cent. amongst 106 cases, and he mentions an incidence of 40 per cent. in the first 100 cases tested in the Royal Victoria Hospital, Montreal. Bowen and Aaron t~ rel~orted achlorhydria in 29 per cent. of 69 diabetics and Rabinowitch, Fowler and Watson 2~ found achlorhydria in 39 per cent. of 100 diabetics. I t is interesting to note in this connection the considerable number of cases of pernicious anaemia recently reported in diabetics. Joslin st mentions 48 cases in which both diabetes and pernicious anaemia were found combined. We have seen one such case. As regards the value of giving hydrochloric acid by mouth in diabetes when achlorhydria exists, we found that this procedure was of some value in the few patients who complained of gastro- intestinal symptoms, but that it appeared to be of little value otherwise.

To summarise, one may conclude that achlorhydria is a common finding in diabetes mellitus. In two cases of the present series it was accompanied by the non-megalocytie form of anaemia above described.

Achlorhydria in tIyperthyroidivm. Our attention was called to the frequent occurrence of achlor-

hydria in Graves' disease by the gastro-intestinal symptoms, such as flatulence and diarrhoea, of which patients with this malady so frequently complain; moreover, the appearance of the tongue in hyperthyroidism quite frequently suggested absence of gastric HC1, although the definite degree of superficial glossitls seen in the above-mentioned form of non-megalocytic anaemia with achlorhydria was not usually present.

The fractional test-meal examination showed that amongst 47 definite cases of hyperthyroidism, achlorhydria was found in 37, or 78.7 per cent., 4 cases had traces of HC1, 1 had hypochlorhydria, 4 had the normal amount of gastric HC1, and one had hyperchlorhydria. These results are shown in Table 5, which also gives the sex, age, and basal metabolic rate in these cases. Of these patients 41 were males and 6 females; aehlorhydria was present in 4 males and 33 females. Histamin was used in only five cases, but its use in these failed to stimulate the formation of HC1. In practically all of these patients a remission, with marked lowering of the basal metabolic rate, was obtained by the use of iodine in from 4 to 10 drop doses, twice daily, by mouth, and in the majority, microscopic examination of the gland removed at operation showed the changes

106 I R I S H JOURNAL OF MEDICAL SCIENCE

associated with hyperthyroidism or with the iodine remission of the same.

I t is without doubt remarkable that such a high incidence of achtorhydria should be found in hyperthyroidism, and our results obtained since this study was concluded still continue to show a high incidence. Faber 22 found aehlorhydria in 50 per cent. of

pa t ien ts suffering from Graves' disease. Two of these eases of hyperthyroidism with absence of gastric

hydrochloric acid showed the non-megalocytie anmmia, namely, No. 3, Table 2 (No. 9, Table 5) and No. 32, Table 2 (No. 36, Table 5).

Gastro-~t~t~na~ Group. Table 6 shows that out of 100 cases whose main complaints

were referable to the gastro-intestinal traet, 46 had such vague symptoms that, notwithstanding careful investigation, no definite diagnosis beyond the aehlorhydria itself could be made; the symptoms complained of were flatulence and sensations of abdominal distention or discomfort or pain after food, nausea or vomiting, attacks of diarrhoea, soreness of the tongue, or ocea- sionaily, superficial ulceration of the bueeal mucous membrane, regurgitation of food or sour fluid into the mouth, and so forth. Fifteen other cases were diagnosed as det~nlte or probable chronic cholecystitis, ten as viseeroptosis and seven as ehronie gastritis. The remaining patients of this group were given various diagnoses as shown in ehe table. All these c~es were thoroughly investigated clinically, routine gastro-intestinai x-ray or gall-bladder visualisa- tion examinations were made (Dr. J. A. Geraghty), and special laboratory and diagnostic procedures were made whenever indicated. The treatment of gastro-intestinal symptoms associated with achlorhydria by means of oral administration of hydrochloric acid has been recently dis. cussed by Wilkinson and Oliver'S; as we are in sub- stantial agreement with the opinions of those authors on this subject, we need not deal with the matter here beyond saying that where achlorhydria seems to be a direet or indirect cause of gastro- intestinal symptoms the use of dilute hydrochloric acid in 15 to 60 minim doses (with pepsin, if necessary) in a suitable vehicle, thrice daily after food, frequently gives satisfactory results, pro- dded that appropriate attention is paid to whatever additional therapeutic instruetions may be necessary.

Miscellaneous Group. (Table 7).--There were 74 eases in this group. Fourteen were

labelled pulmonary tuberculosis, four amongst them having also chronic nephritis. There were 13 cases of pernicious anmmi& The other members of the group were given various diagnoses as shown in the table. The frequent occurrence of achlorhydria in pulmonary tuberculosis was noted by Faber s2 in 1905.

I t would be hazardous, with the information in our possession,

A CLINICAL STUDY OF A C H L O R H Y D R I A 107

to express an opinion on the causes of aehlorhydria. Faber u thinks it is an expression of gastritis, t raumatic or toxie-ha~mat- ogenous in origin, and brings forward post-mortem evidence to that effect; this matter, however, should be a f ru i t fu l field for investigation. There appears to be a good deal yet to be learned about the physiology of gastric hydrochloric acid, and it must be admit ted that our present clinical methods of s tudying gastric secretion leave much to be desired.

Sum~tary and Conclu~io~

Aehlorhydria, besides being found in a certain proport ion of apparent ly healthy persons, in many cases of gastro-intestinal disease and in odd cases suffering from miscellaneous disorders, is a f requent finding i n diabetes mellitus and a still more frequent occurrence in hyperthyroidism and in the non-megalocytie, " hypochromic " anaemia above described; in the lat ter disease it seems to have causal relationship, either direct or indirect, but in the light of recent work on pernicious anaemia even this surmised causal relationship may not be the complete explanation. At any rate, this non-megalocytie form of anaemia is of f requent occurrence, and its adequate t reatment with iron in the ferrous form by mouth gives satisfactory results.

I t gives me great pleasure to acknowledge in this s tudy the eordial co-'operation of Dr. W. R. 0 'Fa r r e l l , Pathologist to the Hospital, and of Doctors L. K. Malley and M. A. Moriarty, while they were my House Physicians.

Re/erenees. 1. Castle. Am. Jo. Med. Sei., 1929, 178, 748. 2. Castle and Townsend. Am. Jo. Med. Sei., 1929, 178, 764. 3. Castle, Townsend and Health. Am. Jo. Med. Sci., 1930, 180, 305. 4. Barnett. Am. Jo. Med. Sci., 1931, 182, 170. 5. Gompertz and Cohen. Am. Jo. Med. Sci., 1929, 177, 59. 6. Bennett and Ryle. Guy's Hosp. Rep., 1921, 71, 286. 7. Baird, Campbell and Hearn. Guy's Hosp. Rep., 1924, 74, 339. 8. Conner. Jo. Am. Med. Assoc., 1930, 94, 606. 9. Vinson. Minnesota Med., 1922, 5, 107.

10. Mettier and Minor. Am. Jo. Med. Sci., 1931, 181, 25. 11. Kelly. Jo. Laryng. and Otol., 1919, 34, 289. 12. Witts. Practitioner, 1930, 124, 348. 13. Witts. Guy's Hosp. Rep., 1930, (July), 253. 14. Moore. Irish Jo. Med. 8ci., 1930, (Sept.), 539. 15. Moore. Brit. Med. Jo.~ 1930, i, 698. 16. Davies. Lancet, 1931, li, 385. 17. Faber. Berlin. Klin. Wochschr., 1913, i, 598. 18. Joslin. Nelson's Loose-Lea/ Medicine, Nov., 1929. 19. Bowen and 'Aaron. Arch. Int. Med., 1931, 47, 384. 20. Rabinowitch, Fowler and Watson. Arch. Int. Med., 1931, 47, 384. 21. Joslin. Nelson's Loose-lea/ Medicine, May, 1931. 22. Faber. Am. Jo. Med. Eci., 1926, 162, 1. 23. Wilkinson and Oliver. Lancet, 1931, i, 66. 24. Faber. Lancet, 1927, ii, 901. 25. Moore, O'Farrell, Malley and Moriarty. Brit. Med. Jo., 1931, ii,

837.

]08 IRISH JOURNAL OF MEDICAL SCIENCE

TABLE L

T o ~ m , , ~ e r of pat~m~ fro, m/~m o,~ or mm, s t~st-,~at 8xaminati,ms w~e d o ~ ; pe,~od I/z/'a7 to 3o /6 r3x- -z , aas .

NI ,mb~ o/ t~se p , ~ i ~ t s u~th i,s~ial ac~hy,~,~a---aTa (za.x%).

Description

Non-megalocytic anaemia of doubtful ~etiology ...

Diabetes mellitus ... Hyper thyroidism ... n

~astro- intes t inal cases

O O m

O I O

m o o

Number with

Achlorhydfla

. ~

Miscellaneous . . . . . .

TOTAL . . . . . . a77-5=,a72*

33 33 37

rr

ioo 74

Total Number

47 83 47

Per cent. showing

Achlorhydria

7 ~ �9 2

39.7 78.7

* NoTz--Two pat ients wi th diabetes, oae wi th hypocalcamia, infanti l ism a n d spontaneous fractures, a n d two with hyperthyroidism had achlorhydri~ and non-megalocytic m ~ m i A and are iacluded under two diagnoses.


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A CLINICAL STUDY OF ACHLORHYI)RIA 113

TABLE I I I . - - A n ~ n i a s with HCI present in stomach contenls or where fractional test-meal was not done.

Description

Splenic anaemia or the Banti syndrome Chronic myelogenous leuk~emia Chronic myelogenous leuk~emia

" Secondary " * anaemia from h~emorrhages (h~emorrhoids, peptic ulcer, uterus, etc.)

" Secondary " anaemia of unknown cause

" Secondary " anmmia in : - Ulcerative colitis Pyloric obstruction (chronic ulcer) Vincent 's angina Hodgkins' disease Septic~emia Rheumatic fever, Hypothyroidism (B.M.R. -- 62 %). Puerperal fever,

Infantilism, hypocalc~emia and te tany Chronic nephritis Chronic cholecystitis Lung and bone tuberculosis Rheumatoid arthritis Ulcer or diverticulum on cardiac end of

lesser curvature of stomach. Pleural effusion

HC1 in fractional test-meal

Normal Normal Traces

Normal Hypochlorhydria Hyperchlorhydria

Not tested

Normal Traces

Hypochlorhydria Hyperchlorhydria

Not tested

Traces Hyperchlorhydria

Normal Hypochlorhydria

Normal Not tested Traces Not tested Normal Not tested Normal Not tested Normal Normal

Hypochlorhydria

T O T A L . . .

N u m ~ r ~Case8

7 2 2 I 2

I

4 3

" By " Secondary" anaemia is meant an anaemia with a low colour index.


Age No. in

years

TABLE IV.mDiabetes Mellitus and Gastric Hydrochloric Acid.

Fasting HC1 in Sex Blood-sugar fractional Remarks

mg. per cent test-meal

x 67 F. x83

2 65 F. 426 3 56 F2 244 4 47 M. 3z2

5 33 F. z24 6 55 F. 312

7 x7 F. 23o 8 64 F. 286 9 47 F. 33o

to 57 F. H 66 F. xz 48 M. x3 53 F. x4 50 F. x5 ~7 F. x6 64 F. x7 3z M. x8 33 M. x9 4 ~ M. ~o 50 F.

2x x 4 M. 22 4 ~ .

�9 3 36 F. 24 56 M. z5 66 F. 26 40 M. 27 66 . 28 29 M M. 29 69~ �9

30 47 M. 31 54 F. 3z ~ F.

33 25 M. 34 4 x M. 35 5 ~ M. 36 53 M. 37 26 M. 38 6o F. 39 53 ~. 40 24 4~ 50 FI

42 60 F. 43 x9 M.

44 40 M. 45 x6~ M. 46 36 M.

2 1 2 25o 285 2z7 200 263 285 26o 200 357 270

2 2 2 2o6

37o 2o6 200 205 I S I

263 2 2 2

2 2 2 225 27o

278 27O 2oo 230 25 o 215 200 3Z8 2 O O

286

2o6 298 2o8

Achlorhydria

Achlorhydria Achlorhydria Achlorhydria

Achlorhydria Achlorhydria


Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria


Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria


Achlorhydria Traces Traces Traces Traces Traces Traces

Hypochlorhydria Hypochlorhydria

Hypochlorhydria Hypochlorhydria

Hypochlorhydria Hypochlorhydria Hypochlorhydria

Chronic hypertrophic ton. sillitis.

Moderate pyorrhcva alveol. axis.

Moderate pyorrhcea alveol. aris.

Postural albuminuria. Diabetic retinitis. High renal glucose thres-

hold ; secondary au~emia (case 24, table 2), wit~ glossitis.

Chronic alcoholism. Pulmonary tuberculosis.

Epigastric pain after food,

Pulmonary emphysema and chronic bronchitis.

Chronic alcoholism for some years.

Chronic alcoholism.

Pyorrhcea alveolaris and dental caries.

Developed secondary anaemia with glossitis (case 28, table 2).

Pyorrhcea alveolaris and obesity.

Pyorrhcea alveolaris and dental caries.

Slight pyorrhcea alveolaris,

Chronic dry otitis media.


T A B L E IV.--Diabaes Mellitus and Gastric HydrocMoric Acid--Continued.

~gl~ Fast ing No. in Sex Blood-sugar

3 ea~ s mg. per cent.

47 49 F. 286 48 45 M. 286 49 9 M. 22o 5 ~ 68 M. 290 5i 6o F. 2 io 52 47 M. 274 53 5 ~ M. 250

54 55 F. 2oo 55 42 M. 250 55 52 M. 227 57 4 ~ F. 308 5 8 47 M. 2oo 59 x6 M. 337 6o 44 F. 278 6I 5 ~ F. 2I 7 62 I2 F. 240 63 x7 F. 333 64 59 M. 235 65 45 F. 286 56 66 F. 250

67 56 F. 256 68 20 F. 3I 7 69 69 M. 235 70 20 F. 317 7I I2 M. 333 72 69 M. I89 73 55 M. 235

74 26 M. 200

75 22 M. 312 76 22 M. 274 77 6x M. 2xo

78 22 M. 274 79 ~3 M. 312 80 20 F. 2oo 8I 61 M. 235 82 6x M. 345 83 42 M, I96


Hypochlorhydria Hypochlorhydria Hypochlorhydria

Normal Normal Normal Normal

Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal

Normal Normal Normal Normal Normal Normal Normal

Normal

Normal Normal Normal

Normal Normal

iHyperchlorhydria Hyperchlorhydria Hyperchlorhydria Hyperchlorhydria

Remarks

Pyorrhcea alveolaris.

Acute suppurat ive ot i th media.

Chronic otitis media. Chronic otitis media.

Obesity

Severe ketosis on admission,

B . P : 2xo#o 4 on admis~ sion ; on discharge, x64/8o

Gangrene of toe. B.P. 18o/9o ; mild retina]

arteriosclerosis. Bilateral chronic pulmonat N

tuberculosis. Ketosis on admission.

Pyorrhoea alveolaris and dental caries.

Auricular fibrillation.

44 Males. 39 Females. Achlorhydria present in 2o Females a~l z 3 Malo|.


TABLE V.--Hyp~hyroidism and GasWir HydroeMorir Add.

~ Ag~ No. I in Sex B.M.R.

yem s per cent.

x 32 F. + 7 5 2 3 x F. + 8 6

3 25 F. + 6 2 48 F . + 7 5 29 F. + 9 0

6 2 2 F. + 9 I

7 43 F. + x x 2 8 x6 F. + 5 7 9 39 F. + 4 9

xo 46 F. + 5 2 xx 46 F. + 3 8 xz 4 ~ M. + 5 5 x3 56 M. + 4 ~

x4 53 F. x5 34 F.

x6 5 ~ F. x7 50 F. x8 62 F. z9 x8 F. ao 53 F. 2I 32 F. 22 49 F. 23 52 F. :r 2o F.

25 65 M.

26 32 F. 27 45 F. 28 68 M. 29 36 F. 3o 5I F. 3x 38 F. 32 48 F. 33 29 F. 34 3 ~ F. 35 45 F. 36 38 F.

+ 5 5 + 2 5

+37 +37 + 6 x +57 +6o +80 +33 +34 + 6 4

+74

+ 4 x +37 + 4 4 + 5 4 +86 + 6 4 + 6 4 +57 +48 +54 +47

37 I9 F. -]-54 38 5 o F. +38 39 5 a F. ~-io2 4 ~ 4x F. + 5 2 4 x 4 x F. + 8 4 42 4 ~ F. + 5 9 43 23 F. + 3 9 44 3 ~ F. + 5 4 45 29 F. + 4 6 46 27 M. + 5 2 47 54 M, +58



Achlorhydria Achlorhydria Achlorhydria Achlorhydria

Achlorhydria Achlorhydria Ach]orhydria

Achlorhydria AchIorhydria Achlorhydria Achlorhydria


Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria

Achlorhydria

Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria Achlorhydria

Achlorhydria Traces Traces Traces Traces

Hypochlorhydria Normal Normal Normal Normal

Hyperchlorhydria

Remarks

Slight secondary anaemia Haemoglobin 7o%.


Dental caries and pyorrhcea alveolaris.


Moderate secondary anmmia Hmmoglobin, 63%. (Case 3, Table II.)

No goitre apparent, but all other clinical signs o| Graves' disease present.

Serum calcium ; 8.o rag. per cent.

Several carious teeth.

Chronic hypertrophic ton- sillitis.

No goitre apparent, but all other clinical signs ot Graves' disease present.

B.P. I7O/94.

HCI absent after histamin. Pyorrhcea alveolaris. HC1 absent after histamine. Thyroid abscess ; non-meg- locytic anaemia (haemoglobin~ 5o%). (Case 32, Table II.)

Some myocardial injury.

HCI normal after histamin.

4! Females, 6 Males. AehlorhydTia present in 33 Females and 4 Males.


T A B L E VI.mAchlorhydria in patients whose main complainls were referablo to the gastro-intestinal tract.

Chief complaints or major diagnosis

Complain ts such as flatulence and distension after food, abdominal pain or discomfort or py lorospasm after food, nausea and vomi t ing af ter food, a t tacks of diarrhoea, soreness of tongue, regurgi ta t ion of food into the mouth , etc . . . . . . . . . . . . . . . . . . .

Chronic cholecystitis . . . . . . . . . . . . . . . . . . . . . Probable chronic cholecystitis . . . . . . . . . . . . . . . . . . Visceroptosis . . . . . . . . . . . . . . . . . . . . . . . . Nausea, visceroptosis and haemorrhoids . . . . . . . . . . . . Vomit ing and haematemesis . . . . . . . . . . . . . . . . . . Headache, const ipat ion and flatulence . . . . . . . . . . . . Chronic appendicit is . . . . . . . . . . . . . . . . . . . . . Vague gastric symp t om s and possible chronic appendicitis . . . . . . Chronic gastri t is . . . . . . . . . . . . . . . . . . . . . Obesity heart, regurgitation of"food and flatulence, possible gall-

bladder disease ..................... Gastroptosis and haemorrhoids, mild secondary anaemia ...... Epigastric pain after food and constipation ............ Spastic constipation and flatulence ............... Nausea, vomiting and spastic constipation ............ Portal cirrhosis ........................ Ulcerative colitis ..................... Carcinoma of stomach .....................

TOTAL ... . . . . . . . . .

N u m b e r of Cases

4 6 z 3

2 Io

2 2

I

7

g

I I

I s I

4

Ioo


T A B L E VII.--Achlorhydria in miscellar~ous conditions.

Number Chief complaint or major diagnosis of Cases

P u l m o n a r y tuberculos is . . . . . . . . . . . . . . . . . . . . . P u l m o n a r y tuberculos is , v a s c u l a r hype r t ens i on a n d chronic

nephr i t i s . . . . . . . . . . . . . . . . . . . . . Ar res t ed p u l m o n ~ y tubercu los i s a n d seconda ry anaemia . . ,

P u l m o n a r y tuberculosis , s e conda ry a n m m i a and chronic nephr i t i s . . . Vascu la r hype r t ens i on w i t h o u t clinical k idney i n v o l v e m e n t Vascu la r h y p e r t e n s i o n a n d m i l d r e t i n a l ar teriosclerosis (one

t u b e r c u l a r k idney r emoved severa l years ago) . . . . . . . . . Chron ic nephr i t i s w i th va scu l a r hype r t ens i on . . . . . . . . . I m p u r e lipoid nephros i s w i t h mi ld secondary a n m m i a . . . . . . T r a n s i e n t " azo t~emic" nephr i t i s . . . . . . . . . . . . . . . R i c k e t s . . . . . . . . . . . . . . . T e t a n y a n d hypocalc~emia ( t r ans ien t achlor t lydr ia) ' i25) . . . . . . Hypocalc~emia and s p o n t a n e o u s f r ac tu res . . . . . . . . . . . . Hypocalc~emia, h y p o g o n a d i s m a n d s p o n t a n e o u s f r ac tu res ;

s e c o n d a r y anmmia . (Case x8 , Tab le II.) . . . . . . . . . Chron ic bronchi t i s . . . . . . . . . . . . . . . . . . . . . E a r l y por ta l cirrhosis . . . . . . . . . . . . . . . . . . . . . Sept ic tons i l s a n d s inus t a c h y c a r d i a .. . Occas iona l a t t a c k s of syncope, cause u n d i a ~ o s e d : : : ::: ::: Mi t ra l i n c o m p e t e n c y (decompensa t ion) . . . . . . . . . . . . Aur i cu l a r f ibri l lat ion . . . . _ _ . . . . . . . . . Auricular fibrillation, vomiting'and ~1"i~rhosa ......... Obesity heart and chronic bronchitis ............ Obes i t y h e a r t . . . . . . . . . . . . . . . . . . . . . . . . L u m b a g o . . . . . . . . . . . . . . . . . . . . . . . . . . . T u b e r c u l a r b reas t abscess . . . . . . . . . . . . . . . . . . A c u t e l y m p h o i d l e u k e m i a . . . . . . . . . . . . . . . . . . H o d g k i n s ' d isease w i t h m o d e r a t e s econda ry a n m m i a . . . . . . Chron ic m y e l o g e n o u s leuk~emia . . . . . . . . . . . . . . . Chron ic sp lenomegaly , s e c o n d a r y a n m m i a and syphi l i s . . . . . . Acholur ic (h~emolytic) j aund ice . . . . . . . . . . . . . . . Men ingo-vascu la r syphi l i s . . . . . . . . . . . . A c u t e h y p o g l y c m m i a w i t h a m y l a c e o u s dyspeps i a ( ~ a n s i e n t

achlorhydria) (25) . . . . . . . . . . . . . . . . . . . . . Myalgia and pyorrhceal alveolaris ... ............ E m p h y s e m a of left max i l l a ry a n t r u m . . . . . . . . . . . . I n f ec t ed cys t ic k idney . . . . . . . . . . . . . . . . . . Pe rn ic ious a n e m i a . . . . . . . . . . . . . . . . . . . . . A d d i s o n ' s disease . . . . . . . . . . . . . . . . . . . . . M y x c e d e m a . . . . . . . . . . . . Miculitz syndrome'(tra~sient aclalorhydria) (25) .........

9

I I

3 5

I

4 I I

4 I I

I 2 z I I 2 2 I I !

I I I I I I I I

I I I I

X3 I I I

TOTAL . . . . . . . . . . . . . 74

Documents

A clinical study of achlorhydria