456

ENDOCARDIAL FIBROSIS OF UNKNOWN

ORIGIN

JOHN B. PENFOLDM.B. Durh.

CONSULTANT PATHOLOGIST,ESSEX COUNTY HOSPITAL, COLCHESTER

ENDOCARDIAL fibrosis can occur in both infants andadults.

In infancy, there is gross thickening of both fibrousand elastic elements in the endocardium, with little orno inflammation or involvement of the myocardium.The condition is known as fibroelastosis or foetal endo-carditis ; and, though its origin is obscure, Still andBoult (1956), using electron microscopy, have recentlydemonstrated superficial deposition of fibrin.

In adults idiopathic endocardial or endomyocardialfibrosis is generally rare, but may be common in Africa

Fig. I—Interior of ventricles showing patchy endocardial fibrosis. Themyocardium is not involved.

(Ball et al. 1954). It differs from infantile fibroelastosisin appearance and does not seem to be so well-defined.

Descriptions vary, but there is usually an increase infibrous tissue in the endocardium and to a varyingextent in the neighbouring myocardium. The elastictissue is ordinarily unaffected, and there is little or noinflammatory reaction.

In the following case of the adult type, thenotable features were the history of possibleinjury to the heart, the patchiness of thefibrosis, and the absence of elastosis and ofinvolvement of the myocardium.

Case-report

Mr. A, a journalist aged 67, was admitted inMarch, 1956, with increasing breathlessness fortwo months.

In 1914, whilst playing cricket abroad, hewas hit " on the heart" by the ball. He

immediately fell unconscious to the groundand lay there for five minutes. Spectatorsthought he was dead. A foreign doctor who sawhim diagnosed " concussion of the heart " andtreated him with an electric instrument over the

precordium.He served in the Middle East and Gallipoli in

the 1914-18 war, and apart from an attack of" C malaria " ten years after his return home, hewas. well until October, 1954. At that time he hada " strained heart " and nocturnal frequency, andwas admitted to hospital. The heart appearedslightly enlarged, pulse-rate 84, blood-pressure(B.P.) 160/95 mm. Hg. The heart-sounds werenormal and there was no dyspnœa or oedema.

Urinary investigations showed an enlarged prostate and aslight left hydronephrosis.

In January, 1955, he had another attack of " heart strain,"but he was not admitted to hospital.Last Illness

History.-Three months before admission he had becomeincreasingly breathless. During the previous three weekshis ankles had swollen and he had had an occasional haemo-

ptysis ; for two days he had been cyanosed and very breath-less, and had vomited frequently.He ate a normal diet and had no allergy. He had never

been to Africa, apart from war service in Egypt.Examination.—He was a well-nourished man with severe

congestive heart-failure. He had auricular fibrillation with aventricular rate of 120 a minute. A harsh systolic murmurwas heard over the whole cardiac area. The apex-beat was5 in. from the midline in the 6th space ; B.r. 110/80. A blood-count showed a slight polymorphonuclear leucocytosis.Total white-cell count 14,600 per c.mm. (polymorphs 82%,eosinophils nil).

Congestive heart-failure of unknown origin was diagnosed.He died eight days after admission with increasing failure.

Necrops yNourish ment.—Good.Cardiovascular ystem.—Signs of congestive failure were

present. The heart was enlarged (weight 405 g.), mainlybecause the ventricles were dilated. The aorta and coronaryarteries were singularly free of atheroma. The pericardium,myocardium, and valves appeared normal, but there were

several small mural antemortem thrombi in the right auricle.There was a patchy irregular superficial thickening of theendocardium of the left ventricle. The myocardium was notinvolved (fig. 1).A small infarct was found in the lower lobe of the left lung,

with an embolus or possibly a thrombus in the appropriatebranch of the pulmonary artery. There were a few smallacute ulcers on the lesser curve of the stomach near the

pylorus, with 3 oz. of free fresh blood in the lumen. An oldinfarct (2 X 1 × 1 in.) was present in the spleen. Benignenlargement of the prostate gland, a large thin-walled bladder,and bilateral hydronephroses were found.

Histology ,;;;

There was a thick patchy fibrous deposit in the endocardiumcontaining fine fatty granules, but with little or no prolifera-tion of elastic tissue. The myocardium was normal exceptfor some large nuclei (fig. 2).

Discussion

Fibrosis of the parietal endocardium of obscure origincan occur in infancy, childhood, and adult life. The

Fig. 2-Edge of a patch of endocardial fibrosis. The thickening can be seen as afibrosis as the elastic layer is not increased. (Weigert’s elastic stain and eosin. x 70.)

457

fibroelastosis of infancy is probably distinct from thefibrosis of childhood and adult life, but Thomas et, al.

(1954) suggest that they have a common aetiology. UsingVerhoeff’s elastic tissue stain, they found in their adultcases that the thickening of the endocardium was afibroelastosis. They also tested some of the endocardiafrom the adult cases reported by Davies and Ball (1955)from Uganda, and found only a few broken elastic fibres ;they suggested that each of the two series had a differentetiology. The question whether the adult type is afibrosis or a fibroelastosis is important ætiologically.In the case reported here there appeared to be a purefibrosis of the endocardium, with no increase in elastictissue and little or no involvement of the myocardium.Despite a long search, no reports of adult endocardial

or endomyocardial fibrosis in Britain have been found,but recently Watt and Lynch (1956) described a case ofendomyocardial fibroelastosis in a boy of 12. Lennox

(1948) reported a case in which a woman had a parietalendocarditis with swollen and pyknotic endothelial cellsand infiltration of lymphocytes and polymorphs ; the

myocardium was cedematous. She had status asthtnati(-usand eosinophilia, and Lennox suggested that thecondition might have proceeded to fibrosis had shelived.

Adult endocardial and endomyocardial fibrosis, thoughuncommon, has been known for many years, particularlyto the German and Swiss pathologists. It was reportedbriefly as early as 1883 (Nauwerk) and at intervals up to1936-e.g., Kockel 1897, Nagayo 1909, Dewitzky 1911 -12,Hertel 1921, Boger 1929. In 1936 Lofller described2 cases as endocarditis parietalis fibroplastica with

eosinophilia. Since then three large series have been

reported from Africa-40 cases by Bedford and Konstam(1946), 40 by Becker et al. (1953), and 31 hy Davies andBall (1955), who gave an excellent detailed descriptionof the pathology of the condition. On the whole theevidence favours a nutritional cause for the Africancases, but Becker et al. (1953) suggested it was a collagendisease. Gray (1951) described 2 cases in Englishmen

living in Nigeria and advaneecl the idea that as there’, was no nutritional deficiency in his cases and it wascommonest in Africa, it might he due to a tropical

infection. A similar case in an Englishman residentin Africa who had syphilis was reported b-v Edge(1946).Apart from the African series, small numbers have been

reported from Switzerland, Germany, Austria (e.g.,Mumme 1940, Buchler 1941-42, Fossel 1942, Egger1944, Roulet 1944, Berblinger 1948), and America (e.g.,Comeau 1937, MëKusick and Cochran 1952, Smith andFurth 1943, Thomas et al. 1954).The pathological picture in tlre cases reported is by

no means uniform, but a general composite picture canbe made up.The patient is usually a rnan, young or nriddle-aged

rather than old (though the condition lias been describedin a man aged 71). The heart is usually normal in size,but it is occasionally enlarged with dilatation of theventricles rather than hypertrophy. Very occasionallythe enlargement is massive. The pericardium andcoronary arteries are normal. The mural endocardium isthickened either in a sheet-like manner or in plaques.It is usually white or greyish-white. The thickness variesbut can be up to 4 mm., or rarely so great that. the lumenof the chamber is largely obliterated. The left ventricleis most often affected, then the right ventricle, and onlyoccasionally the auricles. The commonest site seems to bethe posterior wall, and the least common the iritei--ventricular septum. The rnitral and tricuspid valves aresometimes involved, probably by extension from thewalls, but the semilunar valves are always free. Thenature of the thickening is still not clear.The majority of reports describe the condition as a

fibrosis, others as a fibroelastosis. Commonly there is no

inflammatory reaction, but in many of the Africa casesthere is a deep layer resembling granulation tissue. Inthe myocardium adjacent to the endocardium, there iscommonly muscular degeneration and an extension of thefibrosis ; more rarely these changes are seen throughoutthe myocardium. In many cases, possibly those of mildertype, only the endocardium is affected. Inflammatoryreaction in the myocardium is uncommon but occasion-ally small collections of small round cells are seen.

Polymorphs are noticeably absent.Thrombus formation on the endocardial fibrosis is

very common and embolism is rarer than would beexpected. Other lesions found at different times else-where in the body include infaret-s, signs of malnutrition,allergic and collagen disorders, and eosinophilia in theperipheral blood. Löffler (1936) first described theeosinophilia and suggested that it died out as the diseaseprogressed. The case presented here showed only some ofthese features, as do the majority of cases. The fullpicture is rare.The setiology is obscure, but there have been many

suggested causes, such as malnutrition or defectiveabsorption (Smith and Furth 1943), allergy (Lomer1936, Lennox 1948), Fiedler’s myocarditis (Bedford andKonstam 1946), tropical infection (Gray 1951), syphilisor antisyphilitic treatment (Edge 1946), extension of theinfantile type to adult life (Thomas et al. 1954), collagendisease (Becker et al. 1953, Watt and Lynch 1956),pulmonary disease (Lenegre and Gerbaux 1952), stretch-ing of endocardium in cardiac hypertrophy (Hertel1921), and initial myocardial disease, virus myocarditis,or direct injury (Davies and Ball 1955). It is generallyagreed that rheumatism and ischaemia do not cause

this disease. The only obvious cause in my patient wasa presumed injury to the heart, when he was struck inthe precordial region by a cricket-ball. I should like toadvance the view, apparently so far unexpressed, thatendocardial fibrosis is the end-result of damage to theendocardium irrespective of the nature of the damage.Endomyocardial fibrosis might then be regarded as

the final result of more severe damage or as the endstage where both the myocardium and endocardium havebeen damaged.The nature of the process is still obscure, but if the

above hypothesis is accepted, the course of the diseasemight follow lines similar to those put forward byDuguid (1946, 1949) for the formation of atherosclerosis.

Briefly, Duguid’s hypothesis is that fibrin deposits are laiddown on the arterial intima and that these are incorporatedin the intima by organisation with a final covering of endo-thelium. The recent paper by Still and Boult (1956) suggeststhat a similar process may occur in infantile fibroelastosis.

The sequence of events in adult endocardial fibrosiswould then be (a) damage to the endocardium by one ofmany possible factors ; (b) deposition of fibrin on theaffected areas ; and (c) organisation of the thrombi andincorporation in the endocardium as an apparent fibrosis.

SummaryA case of adult mural endocardial fibrosis is presented

with the necropsy findings. Its pathology, aetiology, andnature is discussed. It is suggested that it is the end-.result of any damage to the endocardium and that themechanism might accord with Duguid’s hypothesison the formation of atheroma.

My thanks are due to Dr. S. A. Propert for permission topublish the case, to Dr. P. G. Seear for details of the patient’shistory, to Dr. L. W. Proger for his help and advice, and toDr. J. W. Nicholas for the photograph of the specimen.

REFERENCES

Ball, J. D., Williams, A. W., Davies, J. N. P. (1954) Lancet, i,1049.

Becker, B. J. P., Chatgidakis. C. B., van Lingen, B. (1953) Circula-tion, 7, 345.

Bedford, D. E., Konstam, G. L. S. (1946) Brit. Heart J. 8, 236.Berblinger, W. (1948) Schweiz. med. W schr. 78, 829.Boger, A. (1929) Beitr. path. Anat. 81, 441.Büchler, H. (1941-42) Z. klin. Med. 140, 56.

Comeau, W. J. (1937) Amer. J. Path. 13, 277.Davies, J. N. P., Ball, J. D. (1955) Brit. Heart J. 17, 337.Dewitzky, W. (1911-12) Frankfurt. Z. Path. 9, 82.Duguid, J. B. (1946) J. Path. Bact. 58, 207.- (1949) Lancet, ii, 925.

Edge, J. R. (1946) Ibid, ii, 675.Egger, P. (1944) Schweiz. Z. Path. 7, 237.Fossel, M. (1942) Beitr. Path. Anat. 107, 241.Gray, I. R. (1951) Brit. Heart J. 13, 387.Hertel, M. P. (1921) Frankfurt. Z. Path. 24, 1.Kockel (1897) Schmidts Jb. 253, 270.Lenègre, J., Gerbaux, A. (1952) Arch. mal. Coeur, 45, 289.Lennox, B. (1948) J. Path. Bact. 60, 621.Löffler, W. (1936) Schweiz. med. W schr. 66, 817.McKusick, V. A., Cochran, T. H. (1952) Bull. Johns Hopk. Hosp.

90, 90.Mumme, C. (1940) Z. klin. Med. 138, 22.Nagayo, M. (1909) Beitr. path. Anat. 45, 283.Nauwerk, C. (1883) Dtsch. Arch. klin. Med. 33, 210.Roulet, F. (1944) Schweiz. med. W schr. 74, 427.Smith, J. J., Furth, J. (1943) Arch. intern. Med. 71, 602.Still, W. J. S., Boult, E. H. (1956) Lancet, ii, 117.Thomas, W. A., Randall, R. V., Bland, E. F., Castleman, E. (1954)

New Engl. J. Med. 251, 327.Watt, J., Lynch, J. B. (1956) Lancet, i, 658.

458

SERUM-POTASSIUM LEVELS AS ANINDEX OF BODY CONTENT

C. T. G. FLEARM.B., B.Sc. Birm.

MEDICAL REGISTRAR, QUEEN ELIZABETH HOSPITAL,BIRMINGHAM

W. T. COOKEM.A., M.D. Camb., F.R.C.P.

PHYSICIAN, GENERAL HOSPITAL, BIRMINGHAM

A. QUINTONM.Sc. Lond., F.Inst.P.

PRINCIPAL PHYSICIST, UNITED BIRMINGHAM HOSPITALS

IN acute experimental depletion of potassium the

-serum -potassium level may show a relationship to theextent of the depletion (Black 1953). In clinical practice,however, not all depletion arises acutely. Moreovera rise in the serum-potassium level at a time of acuteloss of potassium has been reported (Moore et al. 1955).We present here. the results of 110 simultaneous

observations of total exchangeable body-potassium andserum-potassium levels in patients with various com-plaints, mostly either congestive heart-failure or

steatorrhoea.Methods

The methods used for determining exchangeable body-potassium have been detailed elsewhere (Blaiiiey etal. 1954, Flear et al. 1957). The serum-potassium levelswere determined with the ’ Eel’ direct-reading flame-photometer.

Results

Table i shows the distribution of the observationsand diagnoses. Only the patients with congestive heart-failure clinically were oedematous. In the accompanyingfigure the serum-potassium levels are plotted againstthe amounts of total exchangeable potassium in absoluteterms and in relation to weight and to height. In eachcase the values are expressed as percentages of the meannormal values computed from published reports (Flearet al. 1957).

Discussion

The method used estimates the amount of potassiumin the body which has exchanged with its radioactiveisotope 42K from twenty-four to thirty-two hours afterits injection. This total exchangeable mass of potassium(Ke) may be the whole of the body-potassium (Corsaet al. 1950), but Rundo and Sagild (1955) have consideredit to be significantly less. They estimated the total body-potassium from the total gamma-count emitted by thebody. In people not exposed to radioactive materialsthis has been attributed solely to the naturally occurringisotope 4OK, and the total body-potassium can be

computed from the ratio in which 4OK is found to 39K.Total body-potassium was about 15% more than Ke.Theoretically this potassium might be either completelyunexchangeable or might exchange at a much slowerrate. We did not detect any further exchange duringthe eight hours following the first twenty-four after

injection of 42K (Flear et al. 1957) ; nor did we detect anyfurther exchange during this period between the body.sodium and 24Na, though studies using the longer.lifeisotope 22Na (Veall et al. 1955) have revealed a slowfurther exchange requiring several days for completion.Whether a similar slow exchange exists with potassiumis unknown. However, whichever possibility is correct,Ke probably represents the fraction of body-potassiummore readily available for metabolic interchanges.The amount of potassium present in the extracellular

fluid of the body constitutes only about 2% of the value

TABLE I-DISTRIBUTION BY DIAGNOSIS OF PAIRED OBSERVA.

TIONS OF TOTAL EXCHANGEABLE MASS OF POTASSIUM (Ke) ANDSERUM-POTASSIUM LEVELS

obtained for Ke. Effectively, then, changes in E,will reilect changes in intracellular potassium. The

exchangeable mass of potassium has therefore been usedto assess the state of the body-potassium, more particu-larly the extent of any intracellular depletion. Itsuse is, however, open to certain criticisms. Firstly,there is the practical difficulty of the variation in K,which occurs from individual to individual and from dayto day within any individual. This variability betweenindividuals to some extent may be mitigated by theseparate consideration of males and females and byreference to body-weight or to height, on the generalprinciples that the sexes reasonably may be expectedto show differences of body content, and that the sizeof the individual may be a factor involved. Sagild (1956)has shown that Ke per kg. of body-weight varies withage.

Change in Ke may take place from a reduction in theamount of potassium within cells or from a reductionin the number of cells. The former constitutes cellulardepletion of potassium, and the latter represents lossof tissue mass. Loss of potassium from cells causes afall in Ke per kg., whereas loss of lean tissue does not.However, these two factors may not be wholly inde-pendent. It is known, for instance, that experimentaldepletion of potassium leads to a secondary loss of leantissue. The value of Ke per kg. may therefore not fullyrepresent the real depletion of potassium. Furthermore,the value for Ke per kg. of body-weight is altered bychange in body composition other than loss of potassium