disease at the time of study. The age range was from 23 to 49 years. All observations were made with the

Transcription

1 OBSERVATIONS ON THE EARLY ELEVATION OF SERUM POTASSIUM DURING RESPIRATORY ALKALOSIS 1 By JOHN B. HICKAM, WILLIAM P. WILSON, AND REGINA FRAYSER (Frm The Departments f Medicine and Psychiatry, Duke University Schl f Medicine, Durham, N. C.) (Submitted fr publicatin Octber 31, 1955; accepted February 9, 1956) Respiratry alkalsis has been reprted t cause bth an increase and a decrease in serum ptassium cncentratin, with the directin f the change depending upn the duratin f alkalsis. Vluntary hyperventilatin fr 3 t 6 minutes has been fund t cause an average increase f.5 meq. per L. in the arterial serum ptassium f nrmal subjects (1), but hyperventilatin fr 25 t 3 minutes causes a mderate fall in serum ptassium (2-. Over lnger perids f time chrnic passive hyperventilatin was nt fund t prduce a cnsistent change in arterial serum ptassium in man (5), althugh it causes a drp in the serum ptassium cncentratin f the dg (6, 7). The decrease in serum ptassium cncentratin which eventually develps during respiratry alkalsis reflects the mvement f ptassium frm an extracellular t an intracellular psitin as part f an inic transfer which has the effect f buffering extracellular fluid (4, 6, 8). The initial increase in serum ptassium during respiratry alkalsis des nt have this effect and appears paradxical. Because epinephrine can cause a transient rise in serum ptassium, it has been suggested that the ptassium rise during respiratry alkalsis may be mediated by secretin f epinephrine ( 1 ). It is the purpse f this reprt t describe sme bservatins n the elevatin f serum ptassium during acute respiratry alkalsis, with particular attentin t the early time-curse f the changes, the surce f the additinal ptassium, and the causative rle f epinephrine. disease at the time f study. The age range was frm 23 t 49 years. All bservatins were made with the subjects recumbent after a rest perid f 1 t 15 minutes. Vigrus, vluntary hyperventilatin was carried ut at a rate as unifrm as pssible fr perids f apprximately 2 minutes. Arterial bld samples were btained frm the femral r brachial artery, jugular samples frm the jugular bulb, and hepatic venus samples by way f an intravenus catheter. The sampling times given in the text are at the apprximate mid-pints f the sampling perids, which usually ccupied 1 t 2 secnds. The ph f whle bld was measured with a Cambridge Mdel R ph meter equipped with an inclsed glass electrde. Measurements were made at rm temperature, usually 25 t 26 C., and the result was crrected t 37 C. by Rsenthal's factr (9). The per cent xygen saturatin f bld was measured by a phtmetric methd (1). The carbn dixide cntent f whle bld was determined by the methd f Van Slyke and Neill (11), and the plasma carbn dixide cntent was estimated frm this value and frm the ph, hemglbin cncentratin, and per cent xygen saturatin by the line chart f Van Slyke and Sendry (12). The plasma CO2 tensin was calculated by the Hendersn- Hasselbalch equatin, using a pk' f 6.11 (13). The whle bld buffer base was estimated frm the nmgram f Singer and Hastings (1. Serum ptassium was measured with an internal standard flame phtmeter (15). Duplicate determinatins using different serum dilutins shwed a mean difference f.9 per cent (S.D. +.7 per cent). Bld glucse was measured by the methd f Nelsn (16). RESULTS The data btained during brief, vigrus hyperventilatin are presented in Table I. The mean arterial serum ptassium cncentratin increased frm 4. meq. per L. at rest t 5.2 meq. per L. after 2 minutes f hyperventilatin. After METHODS hyperventilatin, the serum ptassium rapidly fell The nrmal subjects were male medical students, tward the cntrl level. physicians, and hspital patients withut knwn rganic In several subjects measurements were als 1 This investigatin was supprted (in part) by. a research grant (Public Health Service H-137) frm the frm varius sites. As shwn in Table I, ve- made f the serum ptassium in venus bld Natinal Heart Institute f the Natinal Institutes f Health, Public Health Service, and (in part) by the nus ptassium was higher than arterial ptassium in the hepatic vein, but was lwer in the Life Insurance Medical Research Fund. 61

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4 64 JOHN B. HICKAM, WILLIAM P. WILSON, AND REGINA FRAYSER jugular and brachial veins. After 2 minutes f hyperventilatin the mean increase in hepatic venus ptassium was 2.1 meq. per L. in fur subjects, while the simultaneus increase in arterial ptassium was 1.2 meq. per L. These findings indicate that ptassium is being added t the bld in the splanchnic regin and remved frm the bld in brain and arm. The data are nt adequate t cnclude that the splanchnic regin is the nly significant surce f the serum ptassium rise during early hyperventilatin. Since serum ptassium is knwn t be elevated by brief vigrus exercise (17), measurements f arterial serum ptassium were made in tw subjects (Ns. 8 and 13) during hyperventilatin n 7 per cent and 1 per cent CO2 t prevent respiratry alkalsis. Neither subject shwed a significant change in ptassium cncentratin during this prcedure, althugh bth had the usual rise in serum ptassium during hyperventilatin n air. Sme experiments were cnducted t explre the pssibility that liberatin f ptassium frm the splanchnic regin during hyperventilatin might be mediated by epinephrine r nr-epinephrine. N evidence was btained fr such mediatin. As shwn by the data in Table II, hyperventilatin and.4 mg. f epinephrine intravenusly have diverse effects upn serum ptas- TABLE II * Diverse effects f hyperventilatin and intravenus epinephrine n arterial serum ptassium and bld glucse cncentratin in tw nrmal subjects Arterial serum ptassium Arterial bld glucse Subject State (meq.il.) (mg. %) Rest Hyperventilatin, 2 min Recvery, 5 min S. B. Rest apprx. 3 min min. after.4 mg. epinephrine i.v min. after.4 mg. epinephrine i.v E. R. Rest min. after.4 mg. epinephrine i.v min. after.4 mg. epinephrine i.v Rest apprx. 3 min Hyperventilatin, 2 min, Recvery, 5 min * Serum ptassium values during hyperventilatin are thse reprted in Table I fr these subjects. sium and bld glucse. Hyperventilatin elevates serum ptassium withut changing bld glucse, while epinephrine in these dses elevates bld glucse withut changing serum ptassium. The epinephrine infusin ccupied 3 secnds, and the first samples were drawn 2 minutes after the start f the infusin. Observatins were als made n tw subjects with defects which shuld have interfered markedly with their prductin f epinephrine and nr-epinephrine. An adult wman wh had undergne a bilateral adrenalectmy fr Cushing's syndrme demnstrated a serum ptassium elevatin f.8 meq. per L. after 1-% minutes f hyperventilatin. A middle-aged man with severe, idipathic pstural hyptensin and a nearly fixed heart rate had a serum ptassium elevatin f.6 meq. per L. after 1-% minutes f hyperventilatin. Hyperventilatin did nt alter this patient's heart rate, but he was s sensitive t epinephrine that the intravenus administratin f.3 mg. f epinephrine prvked a transient episde f auricular fibrillatin. Cncmitant with the rise in serum ptassium during hyperventilatin, the nrmal subjects shwed a small mean increase in arterial whle bld buffer base. The change amunted t 1.1 meq. per L. (Table I). This increase was statistically significant (P <.1). In fur subjects this result was cnfirmed by measuring directly the extent f shift induced in the arterial bld CO2 dissciatin curve by 2 minutes f hyperventilatin. Fr this measurement the CO2 dissciatin curve f arterial bld frm the resting subject was laid ut as a straight line n lg-lg paper, utilizing at least 3 pints, ne f which was clse t the CO2 tensin reached during hyperventilatin. Fr btaining these pints arterial bld frm the resting subject was equilibrated in tnmeters at apprpriate CO2 tensins, and the resultant CO2 cntent and ph were measured. The values actually btained fr arterial bld CO2 tensin and cntent after hyperventilatin fr 2 minutes -lay in each case n the alkaline side f this "in vitr" curve. That is, fr the CO2 tensins which were reached during hyperventilatin, the actual CO2 cntents were always greater than thse predicted by the curve. Fr the fur subjects after 2 minutes f hyperventilatin the actual CO2 cntents exceeded the predicted by a mean f 1.4 meq. per L. The differences were

5 SERUM POTASSIUM DURING RESPIRATORY ALKALOSIS 2.3,.9, 1.1, and 1.4 meq. per L. fr subjects N. 6, 8, 13, and 14, respectively. Venus bld frm the varius sites which were sampled als shwed a small increase in whle bld buffer base during hyperventilatin. DISCUSSION These findings cnfirm the reprt (1) that serum ptassium is elevated early in respiratry alkalsis. The present bservatins were made earlier in the curse f alkalsis than thse which have been reprted befre, and the increase in ptassium is smewhat greater. During this time ptassium is being added t the circulating bld frm the splanchnic regin, and is being remved frm the bld in the brain and peripheral tissues, s far as the arm is representative f these. The present data prvide n evidence as t ptassium exchanges elsewhere. Later in respiratry alkalsis the serum ptassium cncentratin falls belw the resting levels as ptassium mves frm an extracellular t an intracellular psitin (4, 6, 8). There is abundant evidence that epinephrine and related substances can cause a transient elevatin in the serum ptassium cncentratin f man and varius experimental animals (18-2), and D'Silva (21) shwed that epinephrine will induce liberatin f ptassium frm the perfused cat's liver. Hwever, the present findings d nt supprt the suggestin that the serum ptassium elevatin f respiratry alkalsis may be mediated by epinephrine r nr-epinephrine. In man, large dses f epinephrine are requi.red t prduce a transient elevatin f serum ptassium, and the ptassium cncentratin then declines belw the cntrl level (18). N such decline ccurred after brief perids f respiratry alkalsis. N changes in bld glucse were bserved. Respiratry alkalsis induced a rise in the serum ptassium cncentratin f an adrenalectmized subject and a subject with idipathic pstural hyptensin. Luft and vn Euler (22) have fund that persns with pstural hyptensin excrete much less epinephrine and nr-epinephrine in respnse t apprpriate stimuli than d nrmal subjects. This evidence indicates that ptassium elevatin ccurs in nrmal subjects during respiratry alkalsis withut the cllateral effects which might be expected if it were mediated by epinephrine, 65 and that the elevatin can ccur in subjects whse ability t prduce epinephrine and nr-epinephrine is greatly impaired. The rise in serum ptassium which ccurs in man when the bld ph is abruptly elevated abve nrmal levels by hyperventilatin smewhat suggests the hyperkalemiia which ccurs in experimental animals when severe respiratry acidsis is abruptly terminated. In the cat (23) and in the dg (24-26) severe respiratry acidsis, caused by breathing high cncentratins f CO, will cause a cnsiderable increase in serum ptassium. When the bld ph is abruptly raised tward nrmal levels by remving the animal t air, marked further hyperkalemia can ccur. In the dg (26), ptassium has been fund t be released frm the liver during this time, but in the cat (23) the phenmenn ccurs even after splanchnic evisceratin. During early hyperventilatin the CO. dissciatin curve f whle bld shifts t a mre alkaline psitin and, crrespndingly, there is a mdest increase in whle bld buffer base cncentratin. The increase in serum ptassium wuld certainly cntribute tward this change, but ther, undetermined, inic transfers may be quite imprtant. Shck and Hastings (27), using finger bld, fund n change in the CO, dissciatin curve during hyperventilatin, but mst f their bservatins dealt with lnger perids f hyperventilatin, lasting 6 t 2 minutes. Nims, Gibbs, and Lennx (28) fund an apparent shift f jugular venus bld t the alkaline side f the in vitr CO2 dissciatin curve during hyperventilatin, but believed that the arterial bld shwed n such change. In the present study, arterial and jugular venus bld shwed similar increases in buffer base cncentratin. SUMMARY AND CONCLUSIONS 1. In nrmal subjects acute respiratry alkalsis induced by hyperventilatin causes a transitry hyperkalemia. In 13 subjects the mean increase in arterial serum ptassium was 1.2 meq. per L. after 2 minutes f hyperventilatin. 2. During early respiratry alkalsis ptassium is added t the circulating bld in the splanchnic regin. 3. During early respiratry alkalsis there is a small increase in whle bld buffer base.

6 66 JOHN B. HICKAM, WILLIAM P. WILSON, AND REGINA FRAYSER REFERENCES 1. Rapprt, S., Stevens, C. D., Engel, G. L., Ferris, E. B., and Lgan, M., The effect f vluntary verbreathing n the electrlyte equilibrium f arterial bld in man. J. Bil. Chem., 1946, 163, Stanbury, S. W., and Thmsn, A. E., The renal respnse t respiratry alkalsis. Clin. Sc., 1952, 11, Singer, R. B., Elkintn, J. R., Barker, E. S., and Clark, J. K., Transfers f cellular catins during acute respiratry alkalsis and acidsis experimentally prduced in man. J. Clin. Invest., 1953, 32, Elkintn, J. R., Singer, R. B., Barker, E. S., and Clark, J. K., Effects in man f acute experimental respiratry alkalsis and acidsis n inic transfers in the ttal bdy fluids. J. Clin. Invest., 1955, 34, Brwn, E. B., Jr., Campbell, G. S., Elam, J. O., Gllan, F., Hemingway, A., and Visscher, M. B., Electrlyte changes with chrnic passive hyperventilatin in man. J. Applied Physil., 1949, 1, Giebisch, G., Berger, L., and Pitts, R. F., The extrarenal respnse t acute acid-base disturbances f respiratry rigin. J. Clin. Invest., 1955, 34, Scribner, B. H., and Burnell, J. M., The effect f respiratry alteratins f ph n the internal equilibrium f ptassium. J. Clin. Invest., 1955, 34, Scribner, B. H., Fremnt-Smith, K., and Burnell, J. M., The effect f acute respiratry acidsis n the internal equilibrium f ptassium. J. Clin. Invest., 1955, 34, Rsenthal, T. B., The effect f temperature n the ph f bld and plasma in vitr. J. Bil. Chem., 1948, 173, Hickam, J. B., and Frayser, R., Spectrphtmetric determinatin f bld xygen. J. Bil. Chem., 1949, 18, Van Slyke, D. D., and Neill, J. M., The determinatin f gases in bld and ther slutins by vacuum extractin and manmetric measurements. I. J. Bil. Chem., 1924, 61, Van Slyke, D. D., and Sendry, J., Jr., Studies f gas and electrlyte equilibria in bld. XV. Line charts fr graphic calculatins by the Hendersn- Hasselbalch equatin, and fr calculating plasma carbn dixide cntent frm whle bld cntent. J. Bil. Chem., 1928, 79, Dill, D. B., Daly, C., and Frbes, W. H., The pk' f serum and red cells. J. Bil. Chem., 1937, 117, Singer, R. B., and Hastings, A. B., An imprved clinical methd fr the estimatin f disturbances f the acid-base balance f human bld. Medicine, 1948, 27, White, J. U., Precisin f a simple flame phtmeter. Analytical Chem., 1952, 24, Nelsn, N., A phtmetric adaptatin f the Smgyi methd fr the determinatin f glucse. J. Bil. Chem., 1944, 153, Keys, A., Exchanges between bld plasma and tissue fluid in man. Science, 1937, 85, Brewer, G., Larsn, P. S., and Schreder, A. R., On the effect f epinephrine n bld ptassium. Am. J. Physil., 1939, 126, O'Brien, G. S., Murphy, Q. R., Jr., and Meek, W. J., The effect f sympathmimetic amines n arterial plasma ptassium and cardiac rhythm in anesthetized dgs. J. Pharmacl. & Exper. Therap., 1953, 19, Muirhead, E. E., Gth, A., and Jnes, F., Sdium and ptassium exchanges assciated with nr-epinephrine infusins. Am. J. Physil., 1954, 179, D'Silva, J. L., Actin f adrenaline n the perfused liver. J. Physil., 1936, 87, Luft, R., and vn Euler, U. S., Tw cases f pstural hyptensin shwing a deficiency in release f nr-epinephrine and epinephrine. J. Clin. Invest., 1953, 32, MacKay, J. L., Effects f a narctic level f carbn dixide n the plasma ptassium and respiratin f cats. Am. J. Physil., 1947, 151, Yung, W. G., Jr., Sealy, W. C., and Harris, J. S., The rle f intracellular and extracellular electrlytes in the cardiac arrhythmias prduced by prlnged hypercapnia. Surgery, 1954, 36, Scribner, B. H., Bgardus, G. M., Fremnt-Smith, K., and Burnell, J. M., Ptassium intxicatin during and immediately fllwing respiratry acidsis. J. Clin. Invest., 1954, 33, Jyner, S. B., Davis, D. A., Yung, D. T., Craige, E., and Welt, L. G., An analysis f the chemical events and their interrelatinships with alteratins in the ECG during respiratry acidsis and alkalsis. J. Clin. Invest., 1955, 34, Shck, N. W., and Hastings, A. B., Studies f the acid-base balance f the bld. IV. Characterizatin and interpretatin f displacement f the acidbase balance. J. Bil. Chem., 1935, 112, Nims, L. F., Gibbs, E. L., and Lennx, W. G., Arterial and cerebral venus bld changes prduced by altering arterial carbn dixide. J. Bil. Chem., 1942, 145, 189.