YPERNATRAEMIA AND GASTRO-ENTERITIS

129

YPERNATRAEMIA AND GASTRO-ENTERITIS:Practical and Theoretical Considerations

DONALD B. [CHEEK, M.D., D.Sc.*(From the Department of Pediatrics, the University of Texas Southwestern Medical School, Dallas, Texas)

I831 the classical account by Latta concerningeffect of intravenous fluid containing sodiumride and bicarbonate on patients with cholera

ed in the Lancet.27 His description of theto life of shocked, moribund and comatose

ents could at that time only have been regardedincredible. It was surprising that his therapy,

on the ingenious experiments of O'Shaugh-28 did not leave a lasting impression. It was

ly a century before such therapy was re-ted.e importance of shock in diarrhoea,30 thefor restoration of acid-base balance,23 and

the replacement of cell electrolyte14 have allived attention during this century. Alongknowledge concerning potassium has come

realization that renal tubular cells under theof disease or in the face of potassium

letion do not preserve homeostasis. Theal composition of the fluid administered isrtant. The potassium-deficient human oral cannot clear sodium effectively.4, 17, 13, 20, 37ormal rat restricted of (but not deficient in)ium, when given saline to drink rapidly

elops sodium retention in the tissues andue potassium loss.9 Without potassium restric-no changes in body composition occur. The

ure to clear sodium under circumstances ofium deficiency is related, in part, to sodium-

ogen exchange in the renal tubule. Potassiumiency may favour hydrogen ion secretion.3

n children with gastro-enteritis the use ofof sodium in the region of 20 mEq./kg.g the first 24 hours of treatment prejudicesreturn to normal acid-base balance and

ours the occurrence of oedema.8 Such changesr in spite of giving 3 mEq. potassium/kg./24

urs. Smaller amounts of potassium, whenbined with similar sodium loads, cause a swing

nn metabolic acidosis to metabolic alkalosis, and

i!Present address: Royal Children's Hospital,am Street, Carlton, N.3, Victoria, Australia.

oedema, hypokalaemia and tetany occur in ioper cent. of patients.35 That oedema can resultin the human in potassium deficiency was clearlydemonstrated by the work of Fourman andHervey.20The above considerations dictate some of the

rationale in our approach to the patient withgastro-enteritis. The majority of patients ex-perience losses of electrolyte that (in terms oftonicity) exceed losses of water. The moreunusual but well recognized, reverse situationwhere water losses exceed sodium loss also hasbeen appreciated.l, 24, 36 We have come to realizemore clearly in recent years the severe disturbancein body composition and vital mechanisms thataccompanies hypertonic dehydration where lossesof water exceed losses of sodium. The serumsodium concentration (which reflects the serumosmotic pressure) can rise to 200 mEq./l.The clinical diagnosis of this latter condition is

diffizult, but failure to make it may be disastrous.Diarrhoea with hypernatraemia has a fourfoldhigher mortality rate than the usual hypotonictype. There is a significant weight loss which isindicative of water loss, but is not commensuratewith the expected clinical picture of dehydration.If the clinical signs of sodium depletion withextracellular fluid deficit are not present (loss ofskin turgor and skin elasticity), then hypertonicityshould be considered. A valuable clue may be thefinding of a dry mucous membrane in the mouth.Rapoport,32 who re-awakened interest in thiscondition, described the tissues as 'putty-like'or as resembling scleraema in severe cases. Fevermay be present. Twitching, irritability or restless-ness with increased or decreased deep tendonreflexes are sometimes observed in hypertonic de-hydration, in contrast to the prostration of patientswith hypotonic dehydration. In severe hypertonicdehydration with hypernatraemia the centralnervous system is involved,17 and xanthochromiain the spinal fluid with increased protein concen-

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130 POSTGRADUATE MEDICAL JOURNAL February 1

tration is a frequent finding. There may be ahistory of sodium chloride ingestion, the motherhaving given salt with water in good faith, but at ahigh concentration. This occurrence is not aconsistent one, and does not account for all cases.Alternatively, and it would seem more often, thehistory will include a report of continued milkfeeding without supplements of water.1 Thekidney is thereby presented with large solute orosmotic loads which, in the face of dehydration(due to stool water loss), cannot be excretedwithout further water subtraction.Serum analyses reveal the usual metabolic

acidosis, but also a sodium concentration fromI6o to 200 mEq./l. and a chloride concentrationthat exceeds I20 mEq./l. Hypokalaemia may bepresent on admission,16 while hypocalcaemia isalso frequent.32 The blood urea is sometimes high.

It is possible for this hypernatraemia andassociated hyperosmolarity of the body fluids toarise during the course of diarrhoea by two distinctmechanisms:

(a) By an extra loss of water (other than viastools) resulting from a renal osmotic diuresis,due either to an extra solute load from continuedmilk feeding or to underlying renal insufficiency.

(b) By a failure of excretion of previous sodiumloads in the presence of potassium deficiency and(possibly) coincidental adrenal stimulation.

(a) Aberrant Water LossWeil and Wallace,38 in the course of studies

on gastro-enteritis and hypernatraemia, wereimpressed by the finding of a low urine specificgravity in several instances. Our experienceover the last year has been the same. On threeoccasions one has seen values as low as I,005with urine taken shortly after admission at a timewhen the serum sodium concentration was I6o to200 mEq./1. Another patient had a urine osmolarityof only 470 mOsm./l. At the same time, a value ashigh as I,200 mOsm.,'l. has been recorded in otherpatients. Colle et al.1 presented data on urineosmolarity in seven infants with gastro-enteritisand hypernatraemia. The values were all below700 mOsm. /1. She has emphasized the super-imposed water loss via renal channels and foundin most instances a history of continued milkfeeding in the presence of diarrhoea. Such con-tinued milk feeding provides a load of solute whichin the face of dehydration claims further amountsof water for excretion (osmotic diuresis). It mustbe re-emphasized that solute requiring excretionalways subtracts body water-the higher thesolute load the greater the volume of urine.33However, since some patients with hyper-natraemia can concentrate their urine maximally,osmotic diuresis is not the only mechanism that

can precipitate hypernatraemia during gasenteritis. Sodium loading in potassium deficieis more pertinent to this latter situation (see beloThat extracellular volume is low has been edenced by the finding of up to 30 per cent. lossvolume in the chloride space in two infants wgastro-enteritis and hypernatraemia.

Following treatment, nitrogen retentionappears and usually no evidence remainsunderlying renal disease is present before or athe episode. During the acute phase renal functwould seem to be impaired, since WeilWallace39 demonstrated in two patients a glomelar filtration rate of io per cent. of normal, and itknown that water deprivation in the normal infleads to a significant fall in glomerular filtrationto failure of proper urine concentration.6 Arclaims that a tubular lesion (dilatation ofcortical tubules) can be seen in the kidneyhypernatraemia, and Finberg and Harrisoreported high levels for blood urea nitrothough this is not always present.32A small percentage of patients that present w

gastro-enteritis, hypernatraemia and nitrogentention have underlying renal disease. Thisbecome apparent by the failure of the acidosisazotaemia to disappear with treatment; or spicion may be aroused by a failure of the childmeasure up to expected growth levels. The hypnatraemia seen in this situation is related alsoosmotic diuresis, since the few remaining nephrohypertrophy and are forced to deal withcustomary nitrogen and solute waste of theof the body. The increased amount of soludelivered to each nephron causes an extravagexpenditure of water. The more solute filterthe more rapid the passage of fluid throughtubules and the less reabsorption of wNater. Recwork emphasizes that the glomerular filtrationthese remaining nephrons is markedly increand hence there is less time for the modifyeffects of renal tubular function.) Apparensodium-conserving mechanisms are more effectthan those related to water under these conditio

In an attempt to reproduce experimenthypernatraemia due to osmotic diuresis and rinsuffciency six rats (250 to 350 g.) were operaon in two stages and seven-eighths of their retissue removed according to the techniquePlatt.29 Drinking water was available. In five rgrowth was interfered with, but progresslowly over the following month. There wasincrease in blood urea-140 mg. to 190 mg.cent. (24 to 32 mOsm. 1.), as compared withnormal value of 30 mg. per cent. (5 mOsm./l.The animals were sacrificed after four weThere was no change from normal in serelectrolyte concentrations. There was no cha


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r960 CHEEK: Hypernlatraemia andi( Gastro-lEnteritis 131

TABLE I

ATRAEMIA AND CHANGES IN BODY COMPOSITION IN A RAT SUBJECTED 'rO OsMOTIC DIURESIS DUE TO REMOVALOF SEVEN-EIGHTHS OF THE RENAL TISSUE

Serum Concentrations (mEq./l. or Urea in milliosmols per litre)

Urea Cls Nas Ks CO, contented .. .. 58.2 I22 170 5.0 10.5ed .. .. 5.0 10 145 4-5 24.0

Total Electrolyte and Water (mEq. or ml. 'Ioo g. of fat-free dry solid (F.F.D.S.)

F.F.D.S. Clt Nat Kt Mgt Cat H,0ted .. 87.3 12.42 17.3 23-5* 9.5 2I0.0 234*

cted .. 87.3 12.47 17.6 26.4 9.4 194.0 25IDerived Data

cation (Na) concentration in E.C.F. = 25 mEq. or mOsm. 1.cation (K) concentration in I.C.F.:-

(total extracellular Cl)2aex2.7%0 of chloride is outside E.C.F. as in normal rat, then E.C.F. volume - 78 c.c.(conc. ClI. interstitial water)

(expected normal 86 c.c.) and I.C.F. volume = 126 c.c. (expected I65 c.c.), then intracellular concentration ofTotal K--(extracellular K)

- I83 mEq. (expected = I57, difference - 26 mEq. or mOsm. Il).I.C.F. volume

significant reduction. Subscript t = total body electrolyte or water. E.C.F. -- extracellular fluid.I.C.F. - intracellular fluid.

ttal body calcium, magnesium, chloride,sum or water. Two animals lost io per cent.y sodium. For the most part there was noin body composition as Platt has predicted

2). The finding emphasizes the ability ofd renal tissue to maintain body com-

ton when drinking water is available. Rat6, however, after three weeks of constantht, suddenly lost 80 g. in six days; the animalthen sacrificed. The data obtained are par-lay pertinent to the problem of hyper-emia.Table i it can be seen that the blood ureaten times normal and acidosis was presenthypernatraemia. There was no significant

ction of total electrolyte except for potassium.water, on the other hand, was 47 c.c. below

expected normal (or below the water of arat possessing the same fat-free dry solid).g that I2.7 per cent. of chloride is non-

acellular for the rat, an amount determined byous experiments,1° it can be seen that io perof extracellular fluid was lost, but as mucho per cent. of intracellular volume. The

emphasize the greater loss of cell waterthe circumstances. While sodium con-

tion was 25 mEq./l. (25 mOsm.) above thed normal, the predicted increase of intra-potassium concentration was almost

same (26 mOsm.). A rise in extracellulartic pressure is offset, no doubt, by a com-

mensurate rise in intracellular osmotic pressure.These data do not predict a shift of sodium intocells to favour this osmotic adjustment.The texture of the skin in hypernatraemia is a

matter of interest and, as mentioned, this texturehas been compared (in severe hypernatraemia) withthat seen in scleraema. The loss of elasticity ofthe skin has been precisely measured in hypotonicdehydration.25, 26 In hypotonic dehydration thegreatest volume loss is from the extracellularcompartment; in hypertonic dehydration the lossis greatest from the cellular phase. That a largeloss of cell water also occurs in scleraema is shownfrom data obtained in a three-month-old infantwith pneumonia, weighing 4.75 kg., having atemperature of Ios5F. and a typical scleraematousskin. Metabolic acidosis was present withouthypernatraemia, but with a CO2 content of I2.ImEq. 'l., a chloride concentration of 114 mEq./l.and pH of 7.1. The total water was 46.7 per cent.of body weight-a severe reduction-while thecorrected chloride space was 28.2 per cent. ofbody weight (a slight reduction, if any). Clearlylosses of water were greatest from the cellularphase. WVeil and XVallace3" found in the courseof balance studies on two patients with gastro-enteritis and hypernatraemia (either during theonset or recovery) that changes in volume wererelated predominantly to the cellular phase. Thetexture of the skin must be related to this unusualdistribution of water loss.


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132 POSTGRADUATE MEDICAL JOURNAL February 41Arguments can be brought forward that super-

imposed water losses in this type of diarrhoea mayoccur via other avenues than the kidney. Stoolsare always hypotonic to plasma, but there is noevidence that the composition of the stools isdifferent in hypernatraemia. Rapoport32 con-sidered that water loss from hyperventilation mightbe substantial, but preliminary examination of theproblem of hyperventilation by Guest et al.22does not endorse this suggestion. The suggestionthat fever increases insensible water loss is valid,but fever is not a consistent finding, nor doesenvironmental heat stress represent a necessaryfactor.1 Heat stress raises skin water losses.Pratt3l originally investigated the renal waterrequirements of the infant and recent informationemphasizes a higher need than for the adult.34

(b) Sodium RetentionHypernatraemia due to excess sodium retention

may be more or less frequent, depending on theamount of sodium used for treatment in variouspaediatric centres. Mention has already beenmade of the failure of adequate excretion of ex-cessive sodium loads during circumstances ofpotassium deficiency, such as in gastro-enteritis.Even under normal circumstances the infant mayhave difficulty in excreting sodium loads.l5, 21Finberg'9 found that hypocalcaemia occurs whensodium loading is associated with potassiumdeficiency. With sodium loading in gastro-enteritiscell water subtraction was demonstrated.8 Hyper-natraemia was not found. However, Skinner andMoll38 demonstrated hypernatraemia with sodiumloading in gastro-enteritis. Many patients have ahistory of excessive intake of salt prior toadmission.39The study of sodium loading in potassium-

deficient rats presents some points of importanceconcerning the understanding of hypernatraemiaand sodium retention.9 The replacement ofdrinking water by isotonic saline does not alterbody composition of the normal rat over a Io-dayperiod. An increase in body sodium content canbe achieved rapidly in the above experiment ifpotassium intake is restricted or if potassiumdeficiency is first induced (by diet) over a previous2--week period. A 20 to 40 per cent. increase inbody sodium results. This increase in amountcannot be augmented by adding sodium-retainingsteroid-desoxycorticosterone acetate (DOCA)-to the experiment. There is a 20 to 30 per cent.loss of body potassium in these experiments, butno change in total magnesium or calcium.Sodium accumulation can also be achieved

rapidly by injecting sodium-retaining steroids(DOCA) into the normal rat on a normal diet, butwith saline for drinking. The loss of potassium is

The Effect of Na Retaining Steroid on the Concentratioesand Distribution of Na in Normal and K Deficient Rats,

Under Conditions of Na LoadingNORMAL RATS K-DEFICIENT RATS

12-a 5 ,/.for - rf d,r,r;, 0.97. Sa/i,eo, - 4dgays fordi..

A/a 17 -.C.F/ A/2a outs/de E.C./A:ECF Ei'Zfrace/lular fu-

- /La. -Serum SodiamConcentz,f,io,perZ.-Lr'

7)

144

2 /

c --

NO D.O.C.A. PLUS D.O.C.A. NO D.O.C.A. PLUS D.O.A.NVas/L- 45 Na:5/L 1/65 ala/L = I50 Na'a/L- 17.E. C. : vo/me476c E.C.Pvo/umeS.0 c.c E.C.F. vo/lme 47.6cc. CF.owf

not large in this last circumstance (9 per cenImportant points in these experiments are shoin Figs. I and 2. The diagrams have beenstructed on the basis of a theoretical 220-g.In this rat the volumes of extracellular and inticellular fluid have been carefully appraiseddetermining the amounts of chloride and sodithat are considered to be non-extracellulIn potassium-deficient rats that were sodiloaded there was no departure from noin total water or in extracellular volume. It canseen from Fig. I that normally 30 per cent.body sodium in the rat is non-extracellular orbones and cells. When potassium deficiencybeen induced and sodium loading is introduthe increase in body sodium is mainly outsideextracellular space. If DOCA is added toexperiment there is a transfer of excess sodiinto the extracellular space and hypernatraedevelops. The second digram of the figure repsents a normal rat on a normal diet, receirisaline plus DOCA. Here we see the best examof this extracellular sodium increase. Indeed,


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mary 196o CHEEK: Hypernatraemnia and Gastro-Enteritis 133Concemtrutloes of Ilitrs ld Extra-colluIr ElectrolyteLoaded, K Deficieat Rats, witl aad witlout D.O.C.A.

(O omA (.220 g)ra)

C.c --rce-tae AdE.C.P. i,t,cwut,,-f -Fl"dd

I.N

~-·;i''\N

I.*. C.F. a A C F.

N-A-

't . NO D.O.C.A. l .O.C. A

iization of sodium outside the extracellularcan be suspected. In this last experimentwas an increase of the extracellular volume

e expense of cell water.Fig. 2 the theoretical intracellular and extra-ar concentrations for Na and K have beenated in the normal and potassium-deficient

the absence of DOCA, but in the presenceum loading, there is enough cellular sodium

e potassium-deficient rat to counterbalancecell potassium loss without assuming that boneum (2.2 mEq.) is contributing to the cells.

is not the case when DOCA is introducedb'he experiment. In an effort to explain thison gap ' cationic amino acids'6 and hydrogenhave been considered as playing a role in thear electroneutrality. One might anticipate areorganization of cell structure when DOCAded to the above experiment (Fig. 2) to in-osmotic pressure and to counter the extra-

ar hypernatraemia. A priori these data suggestadrenal stimulation is particularly deleteriousr circumstances of potassium deficiency and

ium loading by virtue of its ability to inducernatraemia.

It is probable that some children with gastro-enteritis under circumstances of sodium loadingand potassium deficiency have excessive adrenalstimulation or high levels of sodium-retaining hor-mone, particularly as extracellular volume isreduced in gastro-enteritis. Finberg'9 suggeststhat with sodium loading in potassium deficiencythere might be an alteration in the equilibriumbetween bone and extracellular fluid. If sodiumaccumulates on the surface of the bone crystalsit could play an interfering role in the maintenanceof calcium homeostasis, hence the finding ofhypocalcaemia.

Changes in the Central Nervous System inHypernatraemia

Finberg, Luttrell and Redd18 have emphasizedthe frequency with which patients sufferingfrom hypernatraemia and gastro-enteritis demon-strated alteration in consciousness, ataxia,spasticity, increased deep tendon reflexes or con-vulsions. Subarachnoid haemorrhage or subduraleffusion uwere not unusual. Administration ofhypertonic sodium solution to kittens by the intra-peritoneal route produced these same centralnervous system findings, while the serum sodiumconcentration rose to levels of i6o to 200 mEq./l.

Hyper-irritability, ataxia, tremulousness andconvulsions were all recorded. Cerebrospinalfluid was tinged with blood or the fluid wasxanthochromic. Subdural haemorrhage was re-corded and in some instances intraventricularhaemorrhage. Haemorrhage was not noticed else-where in the body. A chemical change wasnoticed in the muscle in so far as sodium wastransferred to the cell and water was lost from thecell. Both of these phenomena would tend to raisethe cell osmotic pressure in a compensatorymanner. Brain cell sodium was not increased andthese workers suggested that in brain cells a break-down of complex ions occurred to raise osmolarity,an occurrence that would cause gross disturbanceof nervous cell function.

Initial Treatment of Gastro-enteritis withHypernatraemia

It should be noted that any sudden reductionof osmolarity of the body fluids will precipitate aconvulsion17 or produce neurologic damage." Themajor needs in fluid therapy would seem to be forwater, glucose, potassium and calcium. Providedurine flow is satisfactory, it has been our policyto use 40 mEq./l. KC1 solution in 5 per cent.glucose at 8 to i o ml./kg. 'hour. Under circum-stances where renal function is in doubt the KCIis replaced by NaCl until urine flow is established.Calcium gluconate is incorporated in thesesolutions.


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134 POSTGRADUATE MEDICAL JOURNAL FebrualWhile sodium chloride, since the time of Latta,

has been one of the most important therapeuticagents in medicine, some of the limitations of itsuse are now recognized.

Finally, it should be mentioned that renal dys-function may be an important factor causing, insome instances, hypernatraemia, particularly if,for reasons as yet not defined, the anti-diuretichormone is temporarily inactivated. Either vagalinhibition or sympathetic stimulation inhibits anti-diuretic hormone.7 A transient diabetes insipiduswould quickly give rise to hypernatraemia undercircumstances of dehydration.

SummaryInformation concerning hypernatraemia dur-

ing the course of gastro-enteritis has been reviewed.This situation can occur because of superimposedlosses of renal water due to continued milk feeding(obligatory solute or osmotic diuresis).Data from animal experiments are presented to

show the changes in body composition, concentra-tion and volume arising from osmotic diuresis(after removal of seven-eighths of the renaltissue). Losses of water are greatest from thecellular phase in this type of dehydration, a situa-tion also shown to be present in a patient with'scleraema.' The tissues in severe hyperna-traemia resemble scleraema.

Hypernatraemia can also arise from sodiumloading during the treatment of gastro-enteritis and in the presence of potassium de-ficiency. Data from rats (normal and potassiumdeficient) from previous experiments have beenrecalculated to show clearly that salt-retainingsteroid (DOCA) in the face of sodium loading(saline for drinking) has a specific effect. DOCAfavours the accumulation of sodium within theextracellular fluid and produces hypernatraemia.This movement of sodium may require the tissuecells to undergo reorganization of structure tomeet osmotic adjustments.

Adrenal stimulation is suggested as an importantfactor for the development of hypernatraemiaassociated with sodium loading in gastro-enteritis.

It is possible that in some instances renal dys-

function and disturbance of anti-diureticecould be involved.

REFERENCESI. ALLOTT, E. N. (I939), Lancet, i, 1035.2. AREY, J. B., and REARDON, H. (I957), Amer. J.

94, 506.3. BERLINER, R. W., KENNEDY, T. J., Jr., and O

(I954), Arch. int. Pharmacodyn., 97, 299.4. BLACK, D. A. K., and MILNE, M. D. (1952), Clin.5. BRICKER, N. S., RICHARD, R. D., LUBOWITZ

STOKES, J. M. (1958), J. clin. Invest., 37, 886. CALCAGNO, P. L., and RUBIN, J. J. (I95I), Ped7. CHARVAT, J., and HOLECEK, V. (i956), Cas. Le

I 1127.8. CHEEK, D. B. (1956), Pediatrics, 17, 839.9. CHEEK, D. B., and WEST, C. D. (I956), J. clin. Invest

io. CHEEK, D. B., WEST, C. D., and GOLDEN, C.Ibid., 36, 340.

II. COLLE, E., AYOUB, E., and RAILE, R. (I958),22, 5.

12. COOKE, R. E., SEGAR, W. E., REED, C., ETZWILEVITA, M., BRUSILOW, S., and DARROW, D.Amer. J. Med., I7, i8o.

13. COOKE, R. E., SEGAR, W. E., CHEEK, D. B., CF. E., and DARROW, D. C. (I952), J. clin. Invest.,

14. DARROW, D. C. (I946), J. Pediat., 28, 5I5.i5. DEAN, R. F. A., and lIcCANCE, R. A. (1949), J.

(Lond.), Io9, 8 I.i6. ECKEL, R. E., and NORRIS, J. E. C. (I955), J. clin. I

933.17. FINBERG, L., and HARRISON, H. E. (I955), PediaI8. FINBERG, L., LUTTRELL, C., and REDD, H

Amer. J. Dis. Child., 94, 543.19. FINBERG, L. (I957), Ibid., 36, 434.20. FOURMAN, P., and HERVEY, G. R. (I955), Clin. Sa21. GAMBLE, J. L., WALLACE, W. M., ELIEL, L., and

DAY, M. H. (I95s), Pediatrics, 7, 305.22. GUEST, G. M., PETTIT, M. D., ARUJO, C.,

COMBS, B., and WITTGENSTEIN, E. ('9Amer. Ped. Soc., Atlantic City, May 8.

23. HARTMANN, A. F. (1928), Amer. J. Dis. Child., 35,24. KERPEL-FRONIUS, E. (1940), Ztschr. ges. exper..l

235.25. LARON, Z., and CRAWFORD, J. D. (1957), Pediatrics,26. LARON, Z. (I957), Ibid., I9, 8I6.27. LATTA (1831), Lancet, ii, 274.28. O'SHAUGHNESSY, W. B. (I831), Ibid., December29. PLATT, R. (1952), Brit. med. J7., i, 13I33.30. POWERS, G. F. (I926), Amer. J. Dis. Child., 32, 232.3I. PRATT, E. L. (1948), Pediatrics, I, i8I.32. RAPOPORT, S. (I947), Amer. J. Dis. Child., 92, I60.33. RAPOPORT, S., BRODSKY, W. A., WEST, C.

MACKLER, B. (I949), Amer. .7. Physiol., Ix634. Report to Committee of Nutrition, American A

Pediatrics (I957), Pediatrics, 19, 339.35. SCHLESINGER, B., PAYNE, W., and BLACK, JiQuart. J. Med., 24, 33.36. SCHMIDT, C. (I850), 'Characteristik der epidemisch

gegenuber Verwandten.' TranssudationsLeipzig, G. A. Rehyer.

37. SCHWARTZ, W. B., and RELMAN, A. S. (I953),!Invest., 32, 258.38. SKINNER, A. L., and MOLL, F. C. (1956), Ame.

Child., 92, 562.39. WEIL, W. B., and \WALLACE, W. MI. (I956),

171.


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YPERNATRAEMIA AND GASTRO-ENTERITIS