patients are included who developed pyelitis during pregnancy and

TOXEMIAS OF PREGNANCY*JOHN P. PETERS

An analysis has been made of the records of all patients whohave entered the New Haven Hospital since 1921 with complica-tions of pregnancy usually classified under the term toxemia. Ofthis group those who suffered only from vomiting in the earlymonths of pregnancy have been excluded, together with a few whoreceived the diagnosis of toxemia, but had such scanty records thatthe nature of their illnesses could not be determined. To the listof accepted toxemias have been added patients who came to the medi-cal service with vascular and renal disorders that appeared to haveoriginated in or followed pregnancy toxemias. The number of thislatter group in which there may be doubt concerning the relation ofthe disease to pregnancy toxemias is extremely small. Finally, 36patients are included who developed pyelitis during pregnancy and,before or immediately after the termination of pregnancy, exhibitedhypertension, edema, or both. Altogether, the whole series com-prises 351 patients. The present paper presents a summary of someof the salient features of these cases.

Detailed studies of certain groups have already been pEublished.It has been pointed out that pyelitis complicating pregnancy is amajor etiologic factor in the production of toxemias.24 Evidencefor this view has been derived from both clinical and pathologicstudies. Altogether 42 cases with outspoken pyelitis (or its end-result, pyelonephrosis) were discovered among patients who hadreceived the diagnosis of toxemia of pregnancy. To these shouldbe added the 36 mentioned above, who, while suffering from pyelitisduring pregnancy, developed hypertension or edema. In the reviewof autopsy material33 it was demonstrated that besides pyelitis, agreat variety of vascular or renal diseases may act as predisposingcauses for toxemias. Pregnancy apparently contributes only a dis-tinctive coloration and an explosive character to these conditions.In both these reports it was shown that the usual clinical classificationsof toxemias have little significance. This was further emphasized inan analysis of so-called eclamptic toxemias.23 Eclampsia, which was

* From the Department of Internal Medicine, Yale University School of Medi-cine, and the Medical Service of the New Haven Hospital.

YALE JOURNAL OF BIOLOGY AND MEDICINE

chosen for particular examination because of its dramatic and reput-edly specific character, could not be differentiated from other tox-emias on the basis of etiology, pathogenesis, or morbid anatomy. Inall three of these papers attention was called to the permanent effectsof toxemias which usually manifest themselves chiefly in arteriolarlesions, which affect especially the kidneys.

Possible remote or immediate etiological factors have been soughtthrough histories. The results are presented in table 1. Unfor-

TABLE I

ETIOLOGY OF TOXEMIAS

No information about past .......................................................Past history reported "negative" .................................................Past history not significant .........................................................

Number of patients1732815

Antecedent conditions Remote ImmediateNephritis or kidney disease .............. 20 (22)*Pyelitis ......... ................ 9 14Arterial disease ......................... 2Scarlet fever ................. ........ 23Tonsillitis ............ ............. 15 1Rheumatic fever or chorea ............. 28t 3Diphtheria ...... 1 3Pneumonia .............. ........... 13Pleurisy .......... ............... 5Empyema ............ ............. 2Mastoiditis .............. ........... 3Other respiratory infections ............ 7 16

* Figures in parentheses include doubtful cases.

Total20 (22)232

2316281313523

23

tunately, information concerning previous diseases of importancewas entirely lacking in 173 instances and in 28 was confined tothe word "negative" or some equally perfunctory phrase. Thisleaves only 150, or 43 per cent, in which etiology can be examinedproperly. Presumably there was a larger proportion of negative his-tories among those from whom information was not secured; butit would be highly improper to assume that none of these had dis-eases of importance preceding their toxemias. Out of the 150patients with satisfactory records 15 gave no histories of possibly

t In addition familial histories of rheumatic heart disease were secured from3 patients.

312

TOXEMIAS OF PREGNANCY

relevant diseases or functional disturbances either remotely orimmediately preceding their first toxemias.

Twenty (possibly 22) gave definite evidence of renal or vasculardisease antedating their first toxemias. This varied from authenticreports of albuminuria or nephritis to renal calculi and nephrectomy.Of the two doubtful cases, one had suffered at one time from painand burning on urination, the other from temporary incontinence ofurine. In addition, 9 preceding their first toxic pregnancies hadpyelitis which recurred during pregnancy and apparently precipitatedtoxemia. Two are known to have had preexisting arterial disease,which manifested itself in one instance in hypertension, in the otherin chorioretinitis. Indubitable pyelitis appeared early in pregnancyin 48 cases. Altogether, then, 45 to 47 patients out of 150 arerecognized from histories alone to have had renal or vascular diseasebefore the pregnancies in which toxemias first appeared. There isreason to believe that this rOle is far from complete. In the tableand this discussion no consideration has been given to conditionswhich did not dearly precede the first attack of toxemia. There isgood evidence in many instances that abnormalities which were dis-covered only during or after an initial toxemia had originated farearlier. This is especially apparent in the cases of pyelitis. Ofthese only 23 are listed in the table, although there were altogether78 in the series. The 55 omitted undoubtedly had pyelitis beforeor during their first toxic pregnancies, but it remained undiscovered.The great majority of them are probably to be found among thepatients without adequate histories. If these are induded, thegroup with antecedent renal or vascular disease becomes 100 (or102), 29 per cent of the total. This must be taken as a minimumfigure. It dearly indicates that the chief factors predisposing totoxemia are disturbances of the kidneys and arteries.

The incidence of other diseases in past histories resembles theusual tabulations of the causes of nephritis, but is not sufficiently dis-tinctive to have particular significance. Rheumatic fever and choreaperhaps appear with unusual frequency: in 19 per cent of thosewith satisfactory histories or 8 per cent of the whole group. Theactual incdence of rheumatic fever, which must lie somewherebetween these two figures, is probably not less than 10 per cent. Inthis category have been included only patients who had frank andunmistakable rheumatic fever or outspoken chorea; the majority hadsigns of heart disease. Three patients had acute manifestations of

313


rheumatic fever during pregnancy which may have had some rela-tion to the development of toxemias. In the autopsied cases"3 itwas proved that one subject died of acute rheumatic nephritis andendocarditis and 2 others had rheumatic mitral lesions. The fre-quency of rheumatic fever in the antecedent histories of toxemicpatients has been noted also by Lawrence."8

In 16 instances toxemias were immediately preceded by acuterespiratory infections. With the close clinical resemblance betweentoxemia and acute nephritis and the fact that autopsy frequentlyreveals acute nephritis in patients who succumb to toxemias,33 thisassociation can not be lightly brushed aside as coincidental. O'Sul-livan22 elicited a history of respiratory infection immediately pre-ceding toxemia in 32 cases out of 67. The doctrine that pregnancytoxemias are endogenous disorders is so firmly ingrained that littleattention has been given to extraneous influences. Nevertheless,autopsy series reveal lesions unmistakably infectious in origin in acertain proportion of cases.4'33 Besides patients with nephritis, thosewith pyelitis must also be mentioned in this connection, since theycompose a group in which toxemia seems to be precipitated by an infec-tious condition. In some of these cases, as in non-pregnant subjects,respiratory infections preceded the onset of pyelitis. These are notlisted in the table under respiratory infections. It is highly prob-able that more assiduous attention would prove that the associationbetween infections and toxemias is far more frequent than thisanalysis indicates. The subject certainly deserves more carefulexamination.

In general, investigation of the histories in this group of casessuggests that the etiological factors predisposing to toxemias are renaland vascular disorders and those diseases which are generallybelieved to give rise to such disorders.

The incidence of antecedent or predisposing conditions was exam-ined also by an attempt to ascertain the status of patients beforethe onset of the first toxemia. The difficulties in the way of suchan analysis should be clear from table 2. Obviously the onlypatients who can be included in the analysis without objection arethose who were seen before and during their first toxemias. Of thewhole group only 293 were seen in the first toxemia and of these107 had had previous pregnancies. Unfortunately, only 9 had beenobserved during these earlier pregnancies. There is nothing butthe statements of the remaining 98 to prove that they had no toxemic

314


TABLE 2

OCCURRENCE AND OBSERVATION OF FIRST TOXEMIAS

First toxemia observed .................... ............................ 293 (31 1)*In first pregnancy ....................... ......................... 185 (210)In subsequent pregnancies ................................................ 107 (126)

Previous pregnancies not observed ......................... ......... 98

First toxemia not observed ................................... ............. 33In first pregnancy ....................... ......................... 9In subsequent pregnancies ................................................ 6No toxemia observed ............................ .................... 7


manifestations during the earlier pregnancies. This reduces the 293to 195. Of these a large proportion were not seen until evidencesof toxemia had appeared. It is not surprising, under these cir-cumstances, that of only 63 out of the total 351 can it be assertedwith any degree of assurance that blood pressure and urine werenormal before, or in the early months of, their first toxemic preg-nancy. It must be added that 7 of this 63 belong to the groupwith records of antecedent renal disease. It is idle to attempt aninterpretation of these figures and there seems to be no dear wayto better such statistical data without a sweeping change in the atti-tude of the lay public as well as the medical profession. The aver-age woman still seeks advice early in pregnancy only if she hasuntoward symptoms.

The fallacy of attempting to read the past history in the symp-tomatology of toxemias has been sufficiently pointed out in earlierpapers. It was shown that toxemias arising from pyelitis may takea frankly eclamptic form,24' 3 that periportal necroses of the liver,degeneration of the renal tubules, and changes in the glomeruli,which are generally considered to be characteristic of eclampsia, maybe found in patients who have had long-standing hypertension andwho present arteriolar lesions of the malignant nephrosclerotic type."8It is equally fallacious to assume that a given patient is free fromrenal or vascular disease because blood pressure and urine at themoment are normal. This is apparent from the records of manyof the patients with recurrent pyelitis of pregnancy24 and in thefollow-up records of many of the edamptic cases.23 It will bebrought out more clearly below, in the discussion of the subsequentcourse of toxemic patients.

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The incidence of recurrences is presented in table 3. Altogether,144 of the 351 patients are known or suspected to have had 213recurrences of toxemias in subsequent pregnancies. There can be nodoubt about 91, because they were observed in more than one

TABLE 3

INCIDENCE OF RECURRENCES,.-Number of --.,Patients Recurrences

Total recurrences ................. ........................ 144213Original toxemia and recurrence seen .................... 91 122Original toxemia not seen ...................................... 2548Some question about recurrence ......................... ..... 2843

No recurrence .............. ........................... 8 (12)*All pregnancies observed ........................................ 7Early pregnancies not observed ......................... ..... 1 (4)

No further pregnancies ..................................... ....57Sterilized ......................................... 2Not sterilized ................... ...................... 35

Patients lost ......................................... 157


toxemia. Another 25 are reasonably certain because the recurrenceswere witnessed and unequivocal histories of previous toxemias weresecured. There is less certainty about the remaining 28 because therecurrences were not observed. There is satisfactory evidence that 8escaped recurrences; 4 others had, in subsequent pregnancies, equivo-cal symptoms and signs: transient hypertension, minimal edema,or slight amounts of albumin in non-catheterized specimens of urine.Thirty-seven are known to have had no pregnancies after the initialtoxemia because they were sterilized, died, or were seen again afterthey had passed the child-bearing age. There is no informationabout subsequent pregnancies of the remaining 157 patients. A cer-tain number, however, can be eliminated on the grounds that theyhad no further pregnancies because they were followed well into thefifth decade, or because they employed contraceptive methods; itmay be assumed that another fraction had recurrences but did notreturn to the New Haven Hospital. In any case it can be statedwithout question that 41 per cent of all toxemic patients had recur-rences. This represents 75 per cent of those who were adequately

316

TOXEMIAS OF PREGNANCY 317

followed and 92 per cent of those who were both adequately fol-lowed up and had further pregnancies. The results are sufficiendyshocking even if it be assumed that all those who were not followedup escaped recurrences. The incidence of recurrences appears tobear no relation to the nature of the initial toxemia. It has alreadybeen shown23 33 that the eclamptic is not immune. Were it nottedious and unnecessary it could be shown in the same manner thatall types of toxemias, however they may be classified, confer thesame tendency to recurrence.

Something is known of the final outcome of 203 cases (see table4). Forty-nine are known to have died: 17 in their first toxemias,

TABLE 4

ULTIMATE OUTCOME

Died ................................................. 49In toxemias ........... ...................................... 27

In first toxemias ............................. .................... 17In later toxemias ............................. .................... 10

From results of toxemias ............................................... ..21From adventitious causes (with residua) ...................... ............ I

Not known to have diedWith residua

Renal and hypertension ................................................. 10Hypertension . .................................................- 43 (46)*Renal ............. ......... .. ......................... 12Questionable ................................................. 2

Recurrent toxemias (subsequent status unknown) ................ ............ 69

No residua after 1 or more years ................................................. 15

Subsequent course unknown .................................... ............. 148


10 in later toxemias, 21 of vascular or renal disease originating intoxemias, and 1 from carcinoma. The last had, before death, defi-nite hypertension and renal disease that had presumably begunduring a toxemia. Sixty-seven (possibly 70) have chronic vascularor renal disease resulting from toxemias. Of these, 10 have hyper-tension with outspoken signs of impaired kidney function; 43 haveconstant and 3 have intermittent hypertension, and 12 have chronicpyonephrosis or hydronephrosis without hypertension. Two have


symptoms suggesting vascular disease without dear-cut objectivemanifestations. In addition, 69 have been seen in recurrent tox-emias, but have not returned for further observation. Thesecan not be definitely relegated to the group with chronic renal orvascular disease; but deserve quite as litde to be placed among thosewho have escaped these disasters. The probabilities are great thatthey will eventually join the chronic sufferers. Only 1 5 are knownto be free from all signs and symptoms a year or more after theirlast toxemia. This leaves 148 who have not been traced. Some ofthese are known to be living, but the state of heart, vessels, and kid-neys has not been ascertained. The toll is terrible enough withoutthem. Of the total 351, 120, or 34 per cent, are either dead orvictims of chronic disease; an additional 69, or 20 per cent, have hadfurther toxemias. At the best only 46 per cent have survived ingood health and only 15, or 7 per cent, of the 203 who were followedare free from disease.

DiscussionThe outstanding results of the inquiry may be briefly sum-

marized. In the first place no evidence has been found, in theanalysis of clinical records or autopsy material, to justify the usualciassifications of toxemias of pregnancy which are based on clinicalsyndromes. This is particularly well illustrated in the examinationof eclampsia.23833 Typical convulsive toxemias, diagnosed clinicallyas eclampsia, have been observed in patients who proved to havepyelitis or pyelonephrosis; characteristic eclamptic lesions were foundin the liver and kidneys of a patient who had presented a purelyhypertensive picture and died of a dissecting aneurism of the aortawithout any signs or symptoms suggesting eclampsia.33 The com-mon features which all toxemic patients present are symptoms andsigns which, if they were viewed without prejudice, would beascribed to disorders of the kidneys and arteries.

Among these disorders may be found pictures that resemble allthe diseases which, outside of pregnancy, give rise to arteriolar dis-ease, hypertension, and functional impairment of the kidneys.Pyelitis plays an unusually important part, probably because thephysiological hydronephrosis of pregnancy renders it peculiarlymalignant. Nephritis and arteriolar sclerosis are also among theleading conditions predisposing to toxemia. In many instances themanifestations and course of the disease are unmistakably those of

318


acute nephritis. Pathological findings again support clinical impres-sions. The sequelae of the toxemias are also those which commonlyresult from renal and vascular diseases.

There is little in all this to support the general impression thatthe toxemias are manifestations of some abnormality of metabolismor of any derangement or discoordination of endocrine functions.Undoubtedly there are in pregnancy certain anatomic and functionalchanges which may heighten the susceptibility of the pregnantwoman to renal and vascular insults. Among these the first wouldseem to be ureteral obstruction, whether this be due to pressure ofthe gravid uterus or to some change in the mucosa and the muscularlayers of the lower ureter. It is clearly recognized that any impedi-ment to the free discharge of urine enhances the risk of infectionof the urinary tract and, by interfering with drainage, reduces thecapacity to eliminate an infection which has already become estab-lished. Furthermore, no one who has had any considerable experi-ence with nephritis has failed to observe the fact that the courseof this disease is unfavorably, often disastrously, affected by partialurinary obstruction.

Studies of chemistry and metabolism have thrown surprisinglylittle light on the nature of toxemias, partly because too much hasbeen expected of simple chemical analyses of the blood; partlybecause investigations have been made too often, not in -an open-minded spirit, but to find support for some preconception; partlybecause the necessity for control studies of normal pregnant womenhas been neglected. Certain changes in the composition of the bloodare regularly found in normal pregnancy. Among these are reduc-tion of the concentrations of albumin,10 21, 25 bicarbonate,8' 15, 20 21 27, 28and sodium, 15, 21, 28 and increase of lipoids6' '" in the blood.These changes are similar in kind to those observed in certain typesof renal disease. Although they are not sufficiently marked to giverise of themselves to any serious symptoms, they may heighten thesensitivity of the pregnant woman to the effects of circulatory orrenal disturbances. Edema in toxemias is quite consistently asso-ciated with exaggerated hypoproteinemia.10 16, 25 Acidosis has beenheld responsible for some of the symptoms of eclampsia;28 it is,however, likelv that the extreme reductions of bicarbonate whichsometimes occur are the result, rather than the cause, of convul-SiO1s.11'832 The same is true of lacticacidemia, which has beenemphasized by certain observers.2'5 Edamptic convulsions have

319


also been attributed to hypoglycemia,31 and to ketonemia.' Actu-ally, the blood sugar in toxemias seldom falls to levels at whichhypoglycemic reactions are likely to occur;17' 29 ketonemia is prob-ably merely an expression of starvation. It is possible that carbo-hydrate reserves are expended with more than the usual rapidity.Against the renal origin of toxemias the absence of non-proteinnitrogen retention is frequently advanced. Actually, in all butminor toxemias the concentration of non-protein nitrogen in theblood is distinctly higher than that of the normal pregnant woman.It has been repeatedly demonstrated that non-protein nitrogen, andespecially the urea-nitrogen fraction in the blood falls in the latermonths of pregnancy."2 13, " A value of 40 mg. per cent, there-fore, which in the non-pregnant female marks only the upper normallimit, in pregnancy may denote a considerable increase over thenormal.

Because periportal necroses are found at autopsy with some fre-quency, and signs of hepatic insufficiency can be demonstrated in acertain proportion of toxemic patients, the liver has received muchattention and by some has been held chiefly responsible for toxemias,or for certain types of toxemias-notably edampsia. It is wellrecognized that in pregnancy liver damage is prone to occur andmay vary from transitory jaundice to fatal atrophy. There is,however, no reason to believe that even the most profound destruc-tion of the liver can produce hypertension and the other vasculardisturbances which characterize toxemias. Clear-cut cases of acuteyellow atrophy present none of the phenomena usually encounteredin toxemias.26 Pathological lesions in the liver, like functionalimpairment, are only irregularly found and seem quite unrelated tothe dinical syndrome of toxemia.1' 4'83

It can not, of course, be denied that pregnancy plays an impor-tant contributory role in the production of toxemias. If these areto be regarded as manifestations of renal and vascular diseases whichare encountered in non-pregnant individuals, it must be admittedthat they assume rather dramatic colors. Pre-existing renal orvascular disease of an apparently benign nature suddenly burstsinto a malignant state; pyelitis culminates in acute hypertension oreclamptic explosions. These conditions outside of pregnancy cangive rise to hypertension, convulsions, edema, and albuminuria; butthese disturbances usually develop gradually. The frequency of

320


toxemias in pregnancy also exceeds greatly the incidence of renaland vascular disease in non-pregnant women of comparable age. If,then, the ultimate etiological agents, infectious or otherwise, are thesame for both groups, the gravid state must increase the sensibility ofthe kidneys and arterioles to the action of these agents.

The nature of the reactions in vessels and kidneys may also bemodified; but the grounds for argument in this respect are lesssecure. The histological changes found in the tubules and glomeruliof a large proportion of patients who die in the acute stages oftoxemia, whether they had eclamptic seizures or not, have certainfeatures which distinguish them from the lesions commonly found inacute nephritis. In fact, they are considered by Bell3 and otherswho have studied them carefully to be quite distinctive. Thesetubular and glomerular changes in our series of autopsies33 appearedin the patients who had unmistakable marks of antecedent vasculardisease or pyelonephrosis. They would seem at first sight to repre-sent a pattern in which the pregnant woman reacts to vascular andrenal injuries. There are, however, too many exceptions to therule to permit any such hasty conclusion without careful reservations.In some cases in the autopsy series conventional pictures of glomeru-lar and diffuse nephritis were seen. Moreover, the late pathologicallesions which apparently originated from toxemias were quite similarto those which develop out of the common types of arterial and renaldisease that afflict non-pregnant women and males. It is at leastfitting to entertain the thought that pregnancy so intensifies theseverity of renal disease that patients, who would ordinarily sur-vive, succumb. The conventional pathologic picture of acute glo-merular nephritis is not entirely consistent with dinical concepts of thedisease. It is inconceivable that the histological lesions which areusually described can undergo complete resolution. On the otherhand, dinical acute glomerular nephritis in the great majority ofinstances appears to leave no demonstrable residua and thereforemust be associated with reversible anatomical reactions. There isnothing to suggest that the tubular and glomerular lesions usuallyfound in the kidneys of patients who die in acute stages of toxemiaare not entirely reparable. Death in acute nephritis outside of preg-nancy generally comes after the disease has become well establishedor else as the result of septicemia which may greatly modify thehistological picture. This hypothesis about the significance of the

321


tubular and glomerular changes in toxemias is advanced with hesita-tion, chiefly as a caution against the rash adoption of the doctrinethat the gravid state per se determines any specific pathologic pattern.

It is quite commonly taught that termination of pregnancy ismarked by rapid resolution of toxemias. If this were the generalrule it would strongly support metabolic theories of the origin oftoxemias. There is, however, no consistency about the effects ofdelivery. In a certain proportion of cases, of course, toxemias-especially those with eclamptic manifestations-seem to be acutelyprecipitated by labor or immediately after delivery. In othershypertension, albuminuria, and other signs of toxemia may persistor become aggravated. In autopsies on certain of these patients whohave survived for a considerable period (e.g., Case 61,70288) typical"eclamptic" lesions may be found in the kidneys. It would be sur-prising indeed, since pregnancy is at least a contributory factor in theproduction of toxemias, if the termination of this condition did nothave a beneficial effect on the course of these disorders. On theother hand, if they were directly and solely referable to some meta-bolic disorder connected with pregnancy, delivery should give reliefmore regularly. Moreover, pathologic lesions which are specificallyconnected with gravidity should resolve rapidly when this is ended.

. A cautious word is needed concerning the part which endocrinedisorders may play in predisposing to, or precipitating toxemias.Since most of the phenomena of pregnancy presumably result from aseries of linked and carefully balanced interactions of the glands ofinternal secretion, there is no denying the fact that the responsibilityfor all the evils of pregnancy can ultimately be laid at the doors ofthese interesting organs. It has even been daimed that the hydro-nephrosis of pregnancy is due not to pressure from the gravid uterus,but to hypertrophy and hyperplasia of the lower segment of theureter which is part of the hypertrophy and hyperplasia that affectthe pelvic organs in general. It is one thing to admit that altera-tions of endocrine activity may be responsible for the changes ofmetabolism which accompany pregnancy, and that these in turn mayprovide the predisposition to toxemias; it is quite another matter toattempt in our present state of knowledge to place the onus on aparticular gland. An attempt has been made"4 to incriminate thepituitary and specifically the basophilic cells-for hypertension.7Even a conclusive demonstration that toxemias are consistently

322


attended by hyperplasia of basophilic cells in the pituitary wouldnot warrant the deduction that basophilism is the cause of these con-ditions. Basophilic accumulations have been found with unusualfrequency in patients of both sexes with hypertension apparendyarising from a great variety of causes.19 It would be quite illogicalto infer that chronic glomerular nephritis, chronic pyelonephritis,arteriolar sclerosis and all the other diseases from which these sub-jects suffered were caused by basophilism. If the association ismore than coincidental it would be more in keeping with recent sci-entific discoveries of the nature of endocrine functions to supposethat the basophilic reactions represent the mechanism through whichthe organism raises the blood pressure in response to a variety ofimpulses.

The implications of this study so far as the treatment of the prob-lem of toxemias as a whole is concerned should be self-evident.Measures that may be taken to save life or to alleviate symptomswhen toxemias have developed can be discovered only by entirelydifferent methods of inquiry and may be given due consideration atanother time. The outstanding fact is that, under present methodsof management, though life may be saved, health is seldom spared.Patients with antecedent renal or vascular disease can not safely becarried through pregnancy. Women who have pyelitis in preg-nancy seldom escape irreparable and enduring damage, if the preg-nancy is allowed to proceed. Treatment seems to influence theprognosis but little, since infections of the urinary tract can not beeradicated in the presence of obstruction of the ureters. Toxemiasof all kinds leave behind them marks that can not be eradicated,usually in the vascular system. Even if these do not manifest them-selves immediately in progressive arterial or renal disease, theyalmost invariably flare up in subsequent pregnancies, causing furtherpermanent damage. This is as true of eclampsia as it is of the mostapparently benign hypertension or the toxemias that give rise onlyto edema and albuminuria. It is quite unlikely that the peculiarlygloomy outcome in this series is referable only to inept treatment.There is reason to believe that the patients here reported receivedbetter than ordinary care. The only treatment, however, which islikely to yield better results, would be the prevention of pregnancyin women with diseases of the arteries and kidneys or those whohave had previous toxemias, and the termination of pregnancy

323

324 YALE JOURNAL OF BIOLOGY AND MEDICINE

immediately upon the appearance of the first signs or symptoms ofhypertension or renal disease familiarly ascribed to toxemias.

Perhaps if such methods were adopted permanent injury mightresult less frequendy. In acute pyelitis of pregnancy, especially,there are grounds for hope in this direction; because, if obstructionof the ureters was not allowed to develop or to persist for any con-siderable period, the infection might be eradicated before it hadestablished itself and before it had permanently deformed theurinary tract.

Attention might well be diverted from preconceived notions ofthe nature of toxemias to a more exact descriptive analysis of theseconditions and their relation to analogous diseases in the non-preg-nant. If they arise from the same etiological factors, as this reportsuggests, it is distinctly worth while to pay more attention in historyand examinations to infectious processes.

BIBLIOGRAPHY

I Acosta-Sisson, H.: A clinicopathologic study of eclampsia based upon thirty-eight autopsied cases. Am. J. Obst. & Gynec., 1931, 22, 35.

2 Anselmino, K. J., and Hoffmann, F.: OYber den Milchsaureumsatz in derSchwangerschaft und seine Beziehungen zum Kohlehydratstoffwechsel,zur Leber-und Schilddriusen-funktion und zum Kreislauf. I. Woherstammt die Milchsaureerh6hung im Blut von Schwangeren? Arch.Gynik., 1930, 142, 289.

3 Bell, E. T.: Renal lesions in the toxemias of pregnancy. Am. J. Path., 1932,8, 1.

4 Bell, J. W.: Postmortem findings in ten cases of toxemia of pregnancy. Am.J. Obst. & Gynec., 1926, 12, 792.

5 Bokelmann, O.: Die Genese der Schwangerschaftsacidose und ihre Stellungim physiologischen und pathclogischen Stoffwechsel der Graviditit. Arch.Gynak., 1926-27, 129, 987.

6 Boyd, E. M.: The lipemia of pregnancy. J. Clin. Invest., 1934, 13, 347.7 Cushing, H.: Hyperactivation of the neuro-hypophysis as the pathological

basis of eclampsia and other hypertensive states. Am. J. Path., 1934, 10,145.

8 Dieckmann, W. J., and Wegner, C. R.: The blood in normal pregnancy.V. Conductivity, total base, chloride and acid-base equilibrium. Arch.Int. Med., 1934, 53, 526.

9 Dieckmann, W. J., and Wegner, C. R.: The blood in normal pregnancy.VI. Plasma cholesterol in milligrams per hundred cubic centimeters,grams per kilogram and variations in total amount. Arch. Int. Med.,1934, 53, 540.

10 Eastman, N. J.: The serum proteins in the toxemias of pregnancy. Am. J.Obst. & Gynec., 1930, 19, 343.

TOXEMIAS OF PREGNANCY 325

11 Gardner, J. A., and Gainsborough, H.: The cholesterol metabolism duringpregnancy. Lancet, 1929, i, 603.

12 Harding, V. J., Allin, K. D., and V7an Wyck, H. B.: Non-protein nitrogenand uric acid values in blood in pregnancy. J. Obst. & Gynec. Brit. Emp.,1924, 31, 595.

13 Hellmuth, K.: Reststickstoffuntersuchungen am Ende der Graviditat, unterder Geburt und im Wochenbett, mit besonderer Beriucksichtigung derGravidititstoxikosen (Schwangerschaftsnierenerkrankungen und Eklamp-sien). Arch. Gynak., 1923, 118, 18.

14 Hoffmann, F., and Anselmino, K. J.: Uber die Entstehung der Nephropathieund Eklampsie der Schwangeren durch iuberfunktion des Hypophysen-hinterlappens. Klin. Wchnschr., 1931, 10, 1442.

15 Kydd, D. M.: Hydrogen-ion concentration and acid-base equilibrium innormal pregnancy. J. Biol. Chem., 1931, 91, 63.

16 Kydd, D. M., Oard, H. C., and Peters, J. P.: The acid-base equilibrium inabnormal pregnancy. J. Biol. Chem., 1932, 98, 241.

17 Laferty, J. M.: The blood sugar in eclampsia. Am. J. Obst. & Gynec., 1931,22, 637.

18 Lawrence, J. S.: The relation of extraneous disease and subsequent organicdefects to the incidence of eclampsia. Am. J. Obst. & Gynec., 1925, 9,351.

19 Leary, D. C., and Zimmerman, H. M.: Basophil infiltration in neurohypo-physis. Am. J. Path., 1937 (to appear).

20 Nice, M., Mull, J. W., Muntwyler, E., and Myers, V. C.: The acid-basebalance of the blood during normal pregnancy and puerperium. Am. J.Obst. & Gynec., 1936, 32, 375.

21 Oard, H. C., and Peters, J. P.: The concentration of acid and base in theserum in normal pregnancy. J. Biol. Chem., 1929, 81, 9. -

22 O'Sullivan, J. V.: Notes on albuminuria in pregnancy and its treatment.Lancet, 1932, ii, 1326.

23 Peters, J. P.: The nature of eclampsia. Yale J. Biol. & Med., 1936/37, 9,233.

24 Peters, J. P., Lavietes, P. H., and Zimmerman, H. M.: -Pyelitis in toxemiasof pregnancy. Am. J. Obst. & Gynec., 1936, 32, 911.

25 Plass, E. D., and Bogert, L. J.: Plasma protein variations in normal and toxemicpregnancies. Bull. Johns Hopkins Hosp., 1924, 35, 361.

26 Stander, H. J., and Cadden, J. F.: Acute yellow atrophy of the liver inpregnancy. Am. J. Obst. & Gynec., 1934, 28, 61.

27 Stander, H. J., and Eastman, N. J.: The hydrogen-ion concentration of theblood in eclampsia. Am. J. Obst. & Gynec., 1930, 20, 822.

28 Stander, H. J., Eastman, N. J., Harrison, E. P. H. Jr., and Cadden, J. F.:The acid-base equilibrium of the blood in eclampsia. J. Biol. Chem.,1929, 85, 233.

Stander, H. J., Eastman, N. J., and Harrison, E. P. H. Jr.: The acid-baseequilibrium of the blood in the late toxemias of pregnancy. Am. J. Obst.& Gynec., 1930, 19, 26.

29 Stander, H. J., and Harrison, E. P. H. Jr.: Carbohydrate metabolism ineclampsia. Am. J. Obst. & Gynec., 1929, 18, 17.

326 YALE JOURNAL OF BIOLOGY AND MEDICINE

30 Stander, H. J., and Radelet, A. H.: The blood chemistry in eclampsia. Bull.Johns Hopkins Hosp., 1926, 38, 423.

31 Titus, P., Dodds, P., and Willetts, E. W.: The fluctuation in blood sugarduring eclampsia and' its relation to the convulsions. Am. J. Obst. &Gynec., 1928, 15, 303.

Titus, P., Willetts, E. W., and Lightbody, H. D.: V. Fluctuations in bloodsugar during eclampsia; report of additional cases. Ibid., 1930, 19, 16.

32 Wirz, P.: Die Wasserstoffionenkonzentration des Blutes wahrend der normalenund pathologischen Schwangerschaft. Arch. Gynak., 1930, 139, 511.

33 Zimmerman, H. M., and Peters, J. P.: Pathology of pregnancy toxemias.(In press.)

patients are included who developed pyelitis during pregnancy and

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