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ANNOTATION

The Efect of Potassium and Calcium onThe Electrocardiogram

The force and general behaviour of cardiac con-traction can be altered in striking fashion underexperimental conditions by varying the physicaland chemical composition of the fluid bathing theheart muscle. Slight increases in alkalinity oracidity bring about a lengthening or shortening ofsystole respectively and influence the transmissionof the impulse in the conduction system. The ioniccontent of extracellular fluid, its historical deriva-tion from its primitive forerunner sea water, andthe importance of changes in its composition tothe economy of the individual have been portrayedlucidly by Gamble (I942).The three cations potassium, calcium and

sodium must be present in fairly inflexible con-centrations if the heart is to beat normally;magnesium and the anion content of extracellularfluid may be important also but they are beyondthe scope of this review. As might be expectedfrom their effect on cardiac muscle, potassium andcalcium when present in abnormal amounts, pro-duce changes in the electrocardiogram, the formerdramatic and specific, the latter less ostentatiousbut none the less characteristic. The individualcontribution of sodium to electrocardiographicchanges is less well understood but, as will be ex-plained later, a low sodium content (hypo-natraemia) appears to potentiate the abnormalitiescaused by excessive potassium. Significant changesin the serum concentration of one electrolyte areunlikely to occur alone; whether variations inother serum electrolytes can be detected or not,they are likely to be present, in addition tofluctuations in intracellular ions not measurable byordinary laboratory methods. The electro-cardiogram reflects the summation of the changesin the ionic environment of the heart, and in thislies its chief application in the management ofelectrolyte imbalance (Merrill et al., 1950)V

Potassium-Hyperkalaemia (hyperpotassaemia)Abnormally high serum potassium levels are

found in renal insufficiency especially when oli-

guria is present, in untreated Addison's diseaseand conditions associated with excessive vomiting,haemoconcentration and shock. Although thebody stores of potassium are reduced in diabeticacidosis and coma, high serum levels are foundfrequently before treatment is begun because ofthe mechanisms mentioned above.

Heart muscle is susceptible in some way topotassium not shared by skeletal muscle. Thisfact has been demonstrated convincingly in dogswhose limb muscles continue to twitch vigorouslyat serum concentrations of potassium sufficient tocause cardiac arrest (Winkler et al., 1939).

Clinical experience tends to support this observa-tion. With excessive or increasing concentrationof potassium in the serum, rapid and dramaticchanges in cardiac rhythm, for example, transitionfrom sinus rhythm to a state resembling ven-tricular flutter, may be recorded graphicallywithout apparent change in the state of the somaticmuscle (Levine et al., I951).The earliest electrocardiographic signs of

potassium intoxication are an increase in ampli-tude and pointing of the T waves and a shorteningof the QT interval.* The changes may be subtleand inconspicuous and their first appearance maybe overlooked unless especially sought for or unlessa control electrocardiogram is available for com-parison. The sequential changes may be sum-marized as follows (Merrill et al., 1950):-

i. Changes in ventricular activation: Tallpointed T waves and first shortening and laterlengthening of QT interval. R waves becomelower and S waves deeper across the precordium.ST segment is depressed in characteristic fashion.

2. Intra-auricular block: Low, wide P wavesprogressing to auricular fibrillation or standstill.

3. Auriculo-ventricular block: Prolonged PRinterval, possibly progressing to higher grades ofauriculo-ventricular block.

4. Intra-ventricular block: Bundle branchblock or diffuse intra-ventricular block progressingto ventricular standstill.

5. Ectopic rhythms: Ventricular premature orescape beats progressing to ventricular tachy-cardia and an undulating ventricular pattern re-

* In this paper the symbol QT implies a correction forheart rate.

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sembling flutter, and finally ventricular fibrillation.Fig. i illustrates the typical electrocardiographic

changes of severe potassium intoxication in a managed 65 with uraemia resulting from chronicglomerulonephritis. At the time of this tracing(Fig. ia) the serum potassium was II.5 milli-equivalents per litre (mEq./L.)* and serum sodium112 mEq./L. No evidence of auricular activity canbe seen. There is diffuse intra-ventricular blockwith low R waves and deep, wide S waves in leadsV2 to V6. The ST pattern is characteristic; theS wave becomes continuous with the upstroke ofT. no ST segment proper being identifiable. TheT waves are tall and pointed and the QT intervalprolonged. The standard and unipolar limb leadsreflect the changes in the chest leads. When theelectrolyte imbalance was corrected the electro-cardiogram returned to its original form which,of course, is grossly abnormal from pre-existingdisease (Fig. ib). This case has been reportedfully elsewhere (Merrill et al., I950).No explanation in electrophysical terms is avail-

able for the development of deep S waves acrossthe precordium in advanced potassium intoxica-tion. Its resemblance to marked clockwise rota-tion of the heart is not supported by clinicalobservation.

Ventricular arrhythmias are a feature of severecases (Fig. 2). They often present a bizarrepattern and are identical with many records ob-tained from the dying heart. A detailed analysisof such arrhythmias has been made elsewhere(Levine et al., 1951).

Relation of Serum Potassium Levels toElectrocardiographic Changes.When an isotonic solution of potassium chloride

is injected at a steady rate by vein into dogs, theserum potassium concentration increases in linearfashion with time, and a sequence of electro-cardiographic changes develops resembling closelythat outlined above. The earliest abnormalitiesappear at a potassium concentratioo of about 7.8mEq./L.; intra-auricular block develops at 9 to I I

*The normal serum potassium concentration is 5mEq.IL. Milliequivalents per litre are obtained bydividing milligrams per litre by atomic weight andmultiplying by valency.

mEq./L. and cardiac arrest at I4 to I5 mEq./L.(Winkler et al., 1938).In man the correlation is much less exact be-

cause of simultaneous variation in concentrationof other electrolytes, chiefly sodium and calcium.There is adequate experimental evidence that somedegree of tolerance to potassium is achieved bysimultaneous administration of calcium (Winkleret al., 1939). The dissociation between the clinicaland electrocardiographic appearances on the onehand and the serum potassium level on the otherappears to be the result more often of depressedserum sodium levels, for serum calcium valuesmay be within normal limits. Fig. 3, reproducedfrom an article by Merrill, Levine, Somervilleand Smith (I950), illustrates the potentiatingeffect of low serum sodium levels on the electro-cardiogram of hyperkalaemia.

If the electrocardiogram was abnormal beforepotassium intoxication developed, the signs ofboth the pre-existing condition and of hyper-kalaemia will be superimposed. However, theinverted T waves of left ventricular enlargementmay be made upright by potassium, while thoseof cardiac infarction may be more deeply inverted(Sharpey-Schafer, I943).

Hypokalaemia (Hypopotassaemia)Here also exact correlation is lacking betweeft

lowered serum potassium levels and electro-cardiographic changes. As Wallace (i949) haspointed out recently, relative changes from onelevel to another are more important than de-parture from the absolute level of 5 mEq./L.

Potassium depletion results from losses in urine,gastric secretion or other body fluids as in pyloricobstruction and excessive vomiting, especially ininfants, and in a variety of other gastro-intestinaldiseases. In diabetic coma, hypokalaemia de-velops from such losses and is aggravated by apoor intake, by dilution of body water withpotassium-free fluids used in treatment and intra-cellular transfer of potassium following glucose andinsulin therapy. In certain types of chronicglomerulonephritis; where tubular reabsorption ofpotassium is deficient while glomerular filtration isunimpaired, hypokalaemia may result (Sherry etal., 1948). Intensive desoxycorticosterone ace-

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tate (DOCA) therapy, especially in Addison'sdisease and certain alkalotic states, encouragespotassium losses. Finally, in familial periodicparalysis, transfers of potassium occur from extra-cellular fluid into the cells without loss in theurine; dramatic and widespread muscular paralysesare associated with a fall, often abrupt, in serumpotassium (Gass et al., 1948).

The chief electrocardiographic abnormalitiesoccurring with hypokalaemia comprise depressionof the ST segments and lowering or inversion ofT waves in all chest leads, with similar changes re-flected to standard and unipolar limb leads (Fig.4); they are generally less specific and moredifficult to recognize than those of hyperkalaemia.The QT interval is prolonged and when the rateis slow enough to allow them to be seen, prominentU waves may appear. The significance of thelatter is not clear, but they appear to be related tothe after-potentials of ventricular contractionwhich in turn are influenced by the potassiumcontent of the serum. The point is discussedelsewhere (Somerville et al., 195 I).

Hypokalaemia is found often with concomitantchanges in concentration of other cations, es-pecially calcium. Additional electrocardiographicabnormalities may be introduced thereby. Lowpotassium may accompany a high serum calciumlevel; the QT interval may then be prolonged orshortened respectively depending on which abnor-mality dominates the picture. In the hypokalaemiaof diabetic acidosis, Martin and Wertman (I947)found the QT interval prolonged whether thetotal calcium or ionized calcium fraction was lowor normal.

The lack of parallelism between the depressionof serum potassium concentration and electro-cardiographic changes is emphasized again. Thenumerous and complex variables involved inhypokalaemic states such as fluctuations in pH andin blood volume and intracellular electrolyte im-balance secondary to extracellular changes, pro-vide a ready explanation. The electrocardiogram,however, as in hyperkalaemia, reflects the summa-tion effects of these factors influencing cardiacmuscle and is a useful guide to clinical progressand management.

Calcium (Hypercalcaemia)Elevated blood calcium is met with in hyper-

parathyroidism, or after excessive administrationof parathormone or irradiated ergosterol. Malig-nant metastases in bone may cause definite but lessmarked hypercalcaemia.When calcium chloride is injected intravenously

at a steady rate into dogs so that there is a linearincrease in serum calcium with time from the nor-mal of 5 mEq./L, a constant sequence of electro-cardiographic changes is encountered (Hoff et al.,-1939):At 7.5 to 33 mEq./L. the rate slows, PR is

increased, QT decreased and T waves lowered.At IZ to 45 mEq./L. the rate increases and

death may follow ventricular fibrillation.If ventricular fibrillation does not supervene a

second slowing process may develop at concentra-tion of 35 to 95 mEq./L. wigtenheral depression ofthe cardiac mechanism and cardiac arrest.

In man electrocardiographic changes follow thisgeneral pattern although such high concentrationsof calcium are not recorded. Clarke (I941) pro-duced bradycardia in normals by intravenous in-jection to Z.5 to 5 gm. of calcium chloride. Thiswas followed by sinus arrhythmia, shifting pace-maker, auriculo-ventricular block and extra sy-stoles. Similar changes, with the addition ofshortened QT interval were recorded in twopatients with hyperparathyroidism, when theserum calcium level was 9 meq./l. (Kellogg andKerr, 1936).

Hypocalcaemiai Depression of the serum calcium follows re-moval or injury to the parathyroid glands, aninfrequent complication of partial thyroidectomy.Similar reduction with or without tetany is foundwith rickets, osteomalacia, pregnancy, coeliacdisease, sprue and other causes of steatorrhoea, andwith certain cases of renal insufficiency with phos-phate retention. When tetany is produced byhyperventilation, no reduction in serum calciummay be noted although the ionized calcium fractionis depressed.

The dominant change in the electrocardiogramini hypocalcaemia is prolongation of the QT in-terval (Fig. 5). Other abnormalities are incon-

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FIG. I.-Electrocardiograms of a caseof potassium intoxication withuraemia. Fig. ia shows thetypical changes of severe hyper-kalaemia (serum potassium: I I.5mEq./L.). When the electrolyteimbalancewas corrected, the tracingreturned to its original form whichis abnormal from pre-existingdisease (Fig. Ib).

G.E.&e68 LEAD V5.JUNE 30, 1949

*

No 121 K 9.0

FIG. 2.-.Electrocardiogram showing b)ventricular arrhythmia occurringwith hyperkalaemia. The pointedT waves. and ST segments arecharacteristic. The rhythm be-came irregular with a lowering ofserum potassium (Fig. 2C). In2d, the tracing has improved, butthe T waves are still pointed andQT is abnormally long (0.46).

C)

Na 127.5 K 8.2

255 o.m

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d)

Na 127.5 K 5.0 ;3 p

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FIG. 3.-Electroqardiograms obtained from four patients with serum potassium elevated toabout the same degree. The changes are more pronounced when the serum sodium isalso depressed than when it is normal.

I

FIG. 4.-Electrocardiogram of hypokalaemia obtained from a woman aged 50 with Addison'sdisease treated for six years with DOCA. The ST segments are slightly depressed inV4-6; T waves are low or flat, and upright U waves are present in all chest leads. TheQT interval is prolonged (0.48).

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FIG. 5 (Courtesy of Prof. A. Kekwick and Mr. R.Vaughan Hudson).-Electrocardiogram (chestleads) of hypocalcaemia obtained from a manwith Riedel's disease of the thyroid and hypo-parathyroidism. A few minutes later he de-veloped tetany. The QT interval is prolonged(0.46) and the T waves flat or widened, especiallyin V4-6. While this pattern is indistinguishablefrom that of hypokalaemia, certain cases ofhypocalcaemia can be recognized by a prolongedST segment rather than a widened T wave.

spicuous and inconstant. Barker et al. (1937)investigated nine patients with hypocalcaemia,three with hypoparathyroidism following thyroid-ectomy and six with renal insufficiency anduraemia. They found the QT interval prolongedin all instances, and by comparing the latter withmechanical systole (the interval between the firstand second heart sounds) showed disproportionatelengthening of electrical systole (QT interval).The increased QT interval of hypocalcaemia

may be indistinguishable from that of hypo-kalaemia; in certain cases they may be differ-entiated by the fact that lengthening resulting

from calcium deficiency involves the ST segment,while in hypokalaemia wide flat T waves areresponsible (Nadler et al., I948).

Table i summarizes the chief effects of calciumand potassium on the electrocardiogram. Aspointed out above, what the electrocardiogramrecords is the summation of effects of electrolyteimbalance involving intra- and extra-cellular con-centrations of different ions. Changes producedthereby may reflect a combination of two abnormalpatterns, for example those of hyperkalaemia andhypocalcaemia. Pre-existing abnormalities willpersist or may be modified further.

TABLE ISUMMARY OF EFFECTS OF POTASSIUM AND CALCIUM ON THE ELECTROCARDIOGRAM

Potassium Calcium

High Low High Low

PR Lengthened - Lengthened -QRS I Lengthened -ST Depressed Depressed - LengthenedT Tall, pointed Low or inverted Low or unchanged -U Prominent -QT At first, shortened, later Lengthened Shortened Lengthened

lengthenedArrhythmias Frequent - May occur

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302 POSTGRADUATE MEDICAL JOURNAL J7une 1951

Summaryi. The main electrocardiographic changes found

with hyperkalaemia are tall pointed T waves;characteristic ST segment depression; intra-auricular, intra-ventricular and auriculo-ventricularblock and prolonged QT interval. In the earlystages the- latter may be shortened. In advancedpotassium intoxication, various forms of. ventricu-lar arrhythmia may supervene.

2. In hypokalaemia the QT is prolonged,prominent U waves appear, ST segments aredepressed and T waves are low or inverted.

3. Hypercalcaemia causes auricular-ventricularblock, shortening of the QT interval and low Twaves. Bradycardia and sinus arrhythmia mayoccur.

4. The main feature of hypocalcaemia islengthening of the QT interval.

5. Abnormal serum concentrations of potassiumand calcium may be present at the same time andboth may influence the electrocardiogram.

6. The electrocardiogram is valuable in thediagnosis and management of electrolyte im-balance since it represents the summation of effectsof ionic disturbances affecting the heart.

Certain observations mentioned above weremade possible by a grant from the National HeartInstitute, United States Public Health Service(Grant No. H-446).

WALTER SOMERVILLE, M.D., M.R.C.P.,Cardiac Department, The Middlesex Hospital.

BIBLIOGRAPHYBARKER, P. S., JOHNSTONE, F. D., and WILSON,

F. N. (I937), Amer. Heart Y., I4, 82.CLARKE, N. E. (I94I), Ibid., 22, 376.GASS, H., CHERKASKY, M., and SAVITSKY, N.

(I948), Medicine, 27, Io5.GAMBLE, J. L. (I942), 'Chemical Anatomy, Physiology

and Pathology of Extracellular Fluid,' Boston.HOFF, H. E., SMITHI, P. K., and WINKLER, A. W.

(1939), Amer. J. Physiol., I25, I62.KELLOGG, F., and KERR, W. J. (1936), Amer.

Heart J., 12, 346.LEVINE, H. D., MERRILL, J. P., and SOMER-

VILLE, W. (I95I), Circulation, in press.MARTIN, H. E., and WERTMAN, M. (I947), Amer.

Heart3J., 34, 646.MERRILL, J. P., LEVINE, H. D., SOMERVILLE,

W., and SMITH, S., 3rd (I9g5o), Ann. intern.Med., 33, 797.

NADLER, C. S., BELLET, S., and LANNING, M.(I948), Amer. Y'. Med., 5, 838.

SHARPEY-SCHAFER, E. P. (I943), Brit. Heart Y.,5, 8o.

SHERRY, S., EICHNA, L. W., and EARLE, D. P.JUN. (I948), Y. Clin. Invest., 27, 556.

SOMERVILLE, W., LEVINE, H. D., and THORN,G. W. (I951), Medicine, 30, 43.

WALLACE, W. M., and MOLL, F. C. (I949)Pediatrics, 4, 287.

WINKLER, A. W., HOFF, H. E., and SMITH, P. K.(1938), Amer. Y'. Physiol., I24, 478.

WINKLER, A. W., HOFF, H. E., and SMITH, P. K.(I1939), Ibid., 127, 430.

ERRATUM

The Editors'regret that in our April number the illustrations to Mr. D. R. K. Reid'sarticle on Hashimoto's Disease appear in wrong order. Figure i should be-figure 4,figure 2 should be figure i and figure 4, figure 2.

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