STUDIES ON EXPERIMENTAL AND CLINICAL HYPOCHLOREMIA IN MAN Joseph B. Kirsner, … , Walter Lincoln Palmer, Kathryn Knowlton J Clin Invest. 1943;22(1):95-102. https://doi.org/10.1172/JCI101373. Research Article Find the latest version: https://jci.me/101373/pdf STUDIES ON EXPERIMENTAL AND CLINICAL HYPOCHLOREMIA IN MAN1 By JOSEPH B. KIRSNER, WALTER LINCOLN PALMER, AND KATHRYN KNOWLTON (From the Frank Billings Clinic, Department of Medicine, University of Chicago, Chicago) (Received for publication July 21, 1942) INTRODUCTION base was measured by a modification of the Stadie-Ross technique (13); the serum was ashed as for the sodium In a recent study (1), it was demonstrated that analysis; the ash was taken up in 45 cc. of water, the severe hypochloremia and alkalosis could be in- bases precipitated with benzidine hydrochloride, and the duced gradually in the dog, by means of continued difference between the titration of the acidity of this loss of chloride, without the development of a filtrate and that of the original reagents used as a meas- ure of the total base. marked azotemia or detectable renal injury. The patients' body weights were checked frequently. Kerpel-Fronius (2), Kerpel-Fronius and Butler The fluid intake and output were recorded daily. The (3), Ambard (4), and Hiatt (5) had previously pH of the urine was determined with a Beckman pH made similar observations in the dog and rabbit. itheter; the chloride content of the urine was measured The purpose of the present investigation was to by the Van Slyke-Sendroy method (14); and the am- monia plus ammonium salts determined by the technique determine whether or not the same situation could of Henriques and S6rensen (15). The volume, pH, and be induced in man. chloride content of the aspirated gastric secretions were measured similarly. METHOD OF STUDY Aspiration of the stomach was discontinued after a severe but safely obtainable state of chloride depletion I. Experimental hypochloremia had been achieved. The body chloride was then replaced Chloride deprivation was produced rather slowly by gradually in case M. S., over a period of 26 days, by the Wangensteen aspiration of the gastric contents, for vary- addition of increasing amounts of salt. The body chlo- ing lengths of time in 2 adult men (Cages M. S. and ride was replaced more rapidly in case W. L. (within 6 W. L.) with pyloric obstruction secondary to duodenal days) by the parenteral administration of saline solution. ulcer. The patients received no food or fluid by mouth during II. Hypochloremia incidental to ulcer therapy the period of chloride withdrawal; 3000 to 4500 cc. of 5 The problem was in 10 per cent glucose in distilled water were administered studied further patients with intravenously each day. The serum chloride, carbon alkalosis and chloropenia complicating the treatment of peptic ulcer. While two factors were operative in this dioxide, pH, and blood urea nitrogen were measured fre- latter quently (6). Renal function in case M. S. was deter- group, i.e., chloride loss and alkali ingestion, these mined by the urea clearance test cases are included because of the absence of nitrogen (7). Measurements retention and because the evidence indicated that the were made also of the serum calcium (8), phosphorus if (9), and potassium (10). The cell volume was deter- major, indeed, not the only, factor in the acid-base mined frequently by hematocrit readings. The plasma disturbance was the hypochloremia. proteins were determined by the Hanna-Campbell method (11), a modified macro-Kjeldahl technique being em- RESULTS ployed for the nitrogen analysis; 4 per cent boric acid I. Experimental hypochloremia was used to absorb the ammonia released. The blood sodium was measured by a modification of the Butler- Case M. S. (Unit no. 204878 (Figures 1 and Tuthill method (12); the phosphate of the serum was 2). A 38-year-old salesman had taken alkalis removed by ignition with ferric sulfate and the sodium intermittently for 5 years for the relief of symp- determined on an aliquot from which the insoluble iron a salt had been removed by centrifugation. The urinary toms from stenosing duodenal ulcer. He had sodium was determined in case M. S. by the same tech- been vomiting for 5 days prior to hospitalization. nique as that used for the serum sodium, modified as to Five per cent glucose in both normal saline and the volume used; ferric salt was added in amounts suf- distilled water was administered intravenously ficient to prevent interference by phosphates. The total during the first 4 days. Continuous Wangensteen 'This study was supported in part by a grant from aspiration of the gastric contents was begun on John Wyeth and Bro., Inc., Philadelphia, Pennsylvania. the 5th day and continued for 96 hours. The 95 96 JOSEPH B. KIRSNER, WALTER LINCOLN PALMER, AND KATHRYN KNOWLTON 0 NORMAL RANGE TOTAL BASE 0 1/ 9 Ifffffff/ff/f/it/ff A/J/z//z//z////A/zzzzzzy//X/zzzA>/zAX//S 0 NORMAL RANIGE BLOOD '/rn/mi/m,iX//// zSODIUM/// , ,, ,X TOTAS BASE (u.Ee./L.) SERUM K(40Mt.13.4-4.9 Eo/L| 1SERUM CA9. " 1.6-- M.GP.C. BsLOOD..SODIUm (u.EQ/L.) SERUM PROTEINS 2 ,/,,,,/,//,//1-A,,/// (G4S.P 0 HEMATOCRIT 0 _R i0 a 0 ~ BLOOD UREA NITROGEN (MG PER CENT) Y//////j.W,/T,NORMAL RANG wbh..* , so 0 |tI/,////g n o to0 FE ~~~~~~~~~~~~~~~~~~~~~~~~~~~.S._.-...**._.. V. O4 0 '0 . 0 SERUM C0, FIG. 1. EXPERIMENT 1. THE EFFECT OF A GRADUALLY INDUCED HYPOCHLOREMIA ON THE SERUM ELECTROLYTES IN MAN gastric contents removed each day were acid, the hospital on the 39th day, at which time the pa- pH ranging from 1.84 to 2.70; the amounts varied tient was receiving 3.7 grams of chloride daily. daily from 1100 to 3090 cc. Wangensteen suction This amount was increased to 5.3 grams daily one was then limited to a period of 10 hours daily, week later, and the chloride intake was main- the amounts withdrawn ranging from 440 to 1200 tained at this level until the experiment had been cc. The intravenous intake of fluid during the concluded. period of gastric aspiration consisted of 5 per cent The lowest serum chloride of 53.8 mM./L. was glucose in distilled water, except for 1500 cc. nor- obtained on the 11th day. The maximum blood mal saline given on the 12th day. This repre- urea nitrogen of 30 mgm. per cent was obtained sented the only chloride (8.1 grams) taken by the at a time when the serum chloride measured 63.6 patient during the interval from the 4th to the mM./L.; the values ranged usually from 14.2 to 16th hospital days. The salt intake was then in- 19.6 mgm. per cent. The blood sodium decreased creased very gradually until discharge from the to 115.2 m.eq./L. and the total base to 133.3 EXPERIMENTAL AND CLINICAL HYPOCHLOREMIA 97 m.eq./L. The serum calcium and potassium were on 5 days. Sodium excretion paralleled the values normal. The urea clearance was not lowered sig- found for chloride ion. Ammonia excretion in nificantly. The patient lost 23 pounds in weight; the urine, as was to be expected, was diminished. the presence of dehydration was further indicated A histamine test performed on the 19th day by the increased hematocrit readings and the high (serum chloride between 65.5 and 68.8 mM./L.) plasma protein values. revealed normal gastric secretion; the pH of the The serum electrolytes, hematocrit, and plasma various samples of gastric juice ranged from 1.31 proteins gradually returned to normal during the to 1.71. An examination of the spinal fluid on period of chloride replacement. The blood urea the 25th day (serum chloride between 68.5 and nitrogen ranged from 8.1 to 14.3 mgm. per cent. 78.8 mM./L.) revealed a clear fluid under normal At the conclusion of the experiment, the patient's pressure. The chloride measured 100.4 mM./L. body weight had returned to its original level. and the total base 141.5 mM./L. (both values mod- The daily volume of urine varied from 775 to 1920 erately reduced). The calcium was 4.8 mgm. per cc., usually exceeding 1000 cc.; the pH ranged cent and the urea nitrogen 16.7 mgm. per cent from 5.9 to 6.85. Its chloride content was mark- (both values normal). edly reduced; no chloride was found in the urine The patient was very weak and listless during M S UNfl mO. 2 MALE AGE 38 DUODENAL ULCER WITH OBSTRUCTION 0 BODY WEIGHT in 0-.*0 (KG) -- * - B0 ULE//////CAONORMAL RANGE /7y I V 0 UREA CLEARANCE (PER CENT AV NORMAL) DILY FLUID INTAKE AND OUTPUT (URINE I GASTRtIC I0) ( CC) ASPIRATIONS in~~~~~~~~~~~~~~~~~~iE 0 N DAILY CHLORIDE INTAKE I AND CHLORIDE LOSS IN GASTRIC AND URINE (GMS.) in CONTENTS AA a I a 0 in III1 -t -d6 m6l Lq ot1I" 0 X-COMPLCTZ AMECMCOC@CLORIK IN URIE 0 .0 I a'' 26 31 II ISI 2IS S OC T NOVNO DEC. FIG. 2. EXPERMENT 1. ADDITIONAL DATA. HYPOCHLOREMIA IN MAN 98 JOSEPH B. KIRSNER, WALTER LINCOLN PALMER, AND KATHRYN KNOWLTON ° \ ,/BLOOD SODIUM (u.EaJL.) f, SERUMI CALCIUM (MG. PER CENT) SERUM PHOSPHORUS NORMAL RANGE (m Eo/L.) / SERUMs POTASSIUM BLOOD UREA NITROGEN (MG. PER CENT) 0 o ,///////// ///////////////// g///. NORMAL RANGE Y/////////////////////////, o M//////// ,////j</// / NORMAL RANGE / SERUM CHLORIDE a (\AMIL) 0 0 . L UNIT NO a5418 MALE AGE 39 0 %D DU1)ODENAL ULCER WITI'HOBSTRUCTION SERUM pH, s S M u_e~~~~~~~~~~~~~ ,............/11, /// 1// ". ,,,,,,.,,,,,, 4ORMAL RANGE SERUM COa AND p Y / / I I .