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JUNE 9, 1928.

Croonian LecturesON THE

INTERPRETATION OF GASTRICSYMPTOMS.

Delivered before the Royal College of Physicians ofLondon

BY CHARLES BOLTON, C.B.E., M.D., D.Sc. LOND.,F.R.C.P. LOND., F.R.S.,

PHYSICIAN TO UNIVERSITY COLLEGE HOSPITAL.

LECTURE I.Delivered on June 5th, 1928.

DISORDERS of the gastric functions are amongst themost ancient maladies recorded in medical literature,and yet no general agreement has hitherto been reachedas to their classification. Galen 1 was apparentlythe first observer to arrange them in groups upwardsof 2000 years ago. He was dissatisfied with thedifferent meanings which the ancients, as he callsthem, gave to the old Greek word ’’ apepsia." whichwas then in general use. He explains that thedigestive function may be conducted weakly althoughin a normal manner, or it may be definitely disordered,as when the food is changed into some strange matternot useful to the body. He says that the absence ofdigestion should be called "

apepsia," a, weak or

delayed digestion " bradypepsia," and a disordereddigestion ’’ dyspepsia." Such was the probableorigin of this vague but expressive term which is incommon use to-day. Galen’s classification evidentlysurvived into the seventeenth century, for it isadopted by several writers of that period. 2 Subse-quently apepsia and bradypepsia dropped out of use,and dyspepsia, instead of being employed as the nameof a particular pathological disorder, came to beused as a symptom-complex representing all themaladies to which the stomach is liable. Cullen,3for example, in 1784 described idiopathic dyspepsiaas being due to local and general causes (food, ill-health, and so on) and symptomatic dyspepsia as dueto organic disease of the stomach or of some otherpart of the body. The same view is expressed in theDictionary of Medicine by Andral and others 4 in1837, and it is expressly stated that in all cases thecause is to be sought for. Brinton, in 18640,:; on theother hand, excludes organic disease from thedefinition of dyspepsia and regarded it as implying aderangement of function only ; and this is the sensein which the term has been most commonly used upto the present time. Dyspepsia has been classifiedin many ways within recent years ; according to themost prominent symptom, the time of onset of thepain, or the character of the eructated material; as

to the kind of food or other supposed cause givingrise to the disturbance ; as to whether the functionswere exaggerated or depressed ; and in many otherways. 1 one of these came into general use, althoughseveral of the more descriptive terms still survive- ’,for example, " flatulent dyspepsia." jA change took place in the conception of dyspepsia

when the modern methods of functional diagnosisbegan to evolve some 50 years ago. The investigationsof the motor and secretory efficiency of the stomachled to the classification of gastric disorders into motor,secretory, and sensory neuroses, each condition beinggiven the status of a separate entity. This proceedingwas not justified, because. generally speaking, theneuroses had no clearly distinguishable clinical typesof symptoms to correspond with them, and thereforetheir use never became general, although here againsome of the terms survive-for example. " hyper-chlorhydria." Neither have our most modernmethods of investigation by the X rays and thefractional test-meal supplied us with an explanationof the symptoms of dyspepsia. They have added

pathology of the stomach, and are indispensable in thediagnosis of organic disease, and in pointing out thegross changes in function resulting from it. Theyhave, however, shown us that the normal variations inanatomy and physiology are so great that it is usuallyimpossible to say by their use whether any abnor-mality is present or not in cases of simple functionaldisturbance. Our methods are imperfect, for the mealsadministered in the investigations are not such as thepatient usually eats, neither is his nervous systemat the time of examination in the same condition ofirritability as when he is following his vocation. Veryoften the same appearances may be seen by the X rayswhether the patient is in pain or not, for the finechanges in muscular tension responsible for the paincannot be appreciated by our methods, more especiallyas hypersensitiveness of the sensory mechanism is animportant factor to be reckoned with. A reactioninitiated by our surgical colleagues has now takenplace. The performance of abdominal operations,quite apart from its aim as a method of treatment,has aided research in many directions, not to speakof independent observations made by individuals.Speaking of gastric symptoms only, it has focusedattention definitely upon organic disease and shownthat several symptom-complexes formerly describedas neuroses are due to this cause. On the other hand,it has demonstrated that these same groups ofsymptoms may be present in the absence of organicdisease, as the operations, at which no demonstrabledisease is found or at which the removal of the supposedorganic cause has brought no relief to the symptoms,demonstrates. It is thus quite impossible in manycases to distinguish the symptoms due to an organicdisease from those exhibited by patients free fromsuch disease, since the same disturbance of functionis caused in each case. The conception of dyspepsiahas thus returned to that of 200 years ago, and it isnow regarded by an increasing number of the membersof our profession as signifying a group of symptomsresulting from functional disturbance of the stomach,as a primary affection, or due to organic disease. Ibelieve that this view is the correct one to adopt, andthat the leading idea to be kept in mind in investi-gating a case of dyspepsia should be the exclusion oforganic disease. Our first object in diagnosis shouldbe to ascertain the part of the gastric mechanismwhich is upset and the disturbance in action whichit shows ; and. secondly, the cause of this disturbance.The first can only be achieved by a thorough examina-tion of the symptoms of the patient, as these affordthe most delicate and the earliest available index ofdisturbed action. In order to do this a clinical classi-fication of dyspepsia is necessary in which the divisionsare made into symptom-groups or syndromes, eachof which is the clinical expression of the disorder offunction of a particular part of the stomach. Thesecond point as to whether the cause of the disturbanceis organic disease or not may be settled offhand inmany cases ; but in view of the fact that organicdisease may be latent as regards characteristicsymptoms an X ray examination is always necessary,if for any reason it is desirable to exclude such adisease as far as possible. Dyspepsia is one of themost prevalent of disorders, and most cases are

examples of simple disturbances of function, so thatit is neither desirabfe nor possible to subject everypatient to further examination than that afforded byclinical means, unless there is some good reason forso doing. The danger of missing a serious organicdisease of the stomach lies, firstly. in the neglect ofa thorough clinical examination ; and, secondly, inallowing unrelieved cases to drift as if of no importanceinstead of resorting to further investigation. Eachdisorder of function requires a different treatment sothat the determination of our first object in diagnosisis necessary before we can cure our patients. Thequestion now arises as to whether it is possible toclassify dyspepsia clinically into symptoms whichrepresent the separate disorders of function of thestomach. The miscellaneous and varied symptoms ofwhich the subjects of dyspepsia complain, further

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- complicated by their different modes of expression andexaggeration, seem to defy classification, and yet thecareful observer must perceive that, out of the massof cases he sees, there are several different combina-tions of symptoms constantly recurring, which appearto indicate that order and regularity really prevail,but that the outstanding features of a given symptomgroup are so very often overshadowed by unimportantdetails that the reverse appears to be the. case. Onegroup has already been named the pyloric syndrome,but it lacks definition. I believe that it is possible toclassify dyspepsia clinically into such symptom groupsand by explaining these in terms of physiology tobuild up a rational pathological physiology of thestomach.The stomach has the functions of receiving the

swallowed food moderately quickly and of deliveringit gradually to the intestine, so that there are twodistinct phases during the digestive process at whichits functions may be interfered with-namely, duringthe filling and during the emptying. We know quitewell which parts of the stomach are concerned withthese two acts and the chain of events occurring duringeach, so that it should be an easy task to explain theclinical manifestations of the disorders which occur,during each phase. This is what I mean by the inter-pretation of gastric symptoms. The functions of thestomach are so coordinated that it works as a wholeand yet a consideration of the symptoms of gastricdisturbance suggest that the disorder commonly beginsin one part and that this part may remain for longperiods the chief centre of irritation, or that theother parts may soon be equally involved so that inall cases we must endeavour to find out if possiblewhere the disorder has begun, as this determines thetype of the malady. This entails a careful history of- each symptom, not only as to the order of its appear-ance in the symptom-complex but also as to anychanges in its character which has appeared since theillness commenced. It is necessary to have a largenumber of cases available in order to obtain asufficiency showing simple combinations of symptoms,from which to form types in the first instance, andfinally to explain the more complicated forms. Withthis end in view I propose to give you the results of astudy of a series of 1000 cases of gastric disturbance.My object being to demonstrate the various ways inwhich the functions of the stomach are interfered with,this series should be free from cases of organic disease.But it is quite impossible to obtain such a series,because we have seen that certain organic diseasesproduce the same symptoms as those we wish to,study, since they upset the functions of the stomachin the same way. Now a disease does this by actingas a focus of irritation to the particular part of thestomach in which it is situated and, so long as it doesnot structurally alter the stomach may be included inour series with advantage, because it tells us exactlywhat symptoms to expect when a given part of thestomach is irritated. The truth of the matter is thatthere are two distinct groups of dyspepsia, defined aswe have agreed upon-the symptoms of interferencewith the functions of the stomach which is (1) structur-ally normal, or (2) structurally abnormal. There is afundamental difference between the two, because itis impossible to study the disturbances of normal’function in an organ so structurally altered as to beincapable of performing these functions. I refer topyloric stenosis, hour-glass stomach, leather-bottlestomach, and the various deformities produced bycarcinoma, and so on; on the other hand, an uncom-plicated gastric ulcer produces its symptoms by acting- as a focus of irritation and so interfering with thenormal functioning of the part in which it is situated.The type of dyspepsia in which the stomach is

anatomically altered can in the majority of cases beexcluded. The series of cases I shall deal with,therefore, includes all those patients with gastricdisturbance, as they come before the physician, inwhom the stomach is capable of performing, and’periodically does perform, its functions normally.Before proceeding to an analysis of these cases I shall

first give a brief account of ii-tv views upon themechanism of production of pain. because it isnecessary to keep this in mind during the considerationof the symptoms ; and also upon the value of localand referred pain as indicating the part of the

apparatus affected.MECHANISM OF PRODUCT]ION OF P<1IB .

Modern research in gastric pathology has shownthat the symptoms constituting dyspepsia are not dueto alterations in the secretion of gastric juice or in thechemical process of digestion, but to alterations in themotor functions of the stomach. So long as thesefunctions are conducted normally and the stomachempties in the normal time it does not matter whetherthe gastric juice is increased or diminished in amount;but if the stomach fails to empty itself normally thensecondary alterations occur in the gastric contents,which add to or modify the symptoms produced bythe motor insufficiency of the stomach.For a great number of years before it was clearly

established 6 that the alimentary canal is insensitive eto the ordinary stimuli which produce touch and painin the skin it was considered that muscular spasmwas the cause of some forms of abdominal pain;and now it is almost universally considered thatvisceral symptoms in general are almost entirelymuscular in origin, and only on occasion originate inthe mucous membrane.The muscular sensations may be grouped under two

headings: (1) Minor sensations, expressed as someform of discomfort or as the feeling of a lump, weight,tightness, or fullness. (2) Pain, varying in degree froma slight ache to very severe pain and described by thepatients in different terms, each expressing the kindand degree of pain they experience. There is no realdifference between these sensations, each expressingin a special way some degree of muscular tension.Each minor sensation may develop into pain, some-times the two alternate at different times, and oftenthe patient cannot say whether the sensation isactually one of pain or not. They are also similar inrespect of the time of their appearance and disappear-ance and of their position. The explanation of thefact that the viscera give rise to pain in morbid condi-tions and yet are insensitive to ordinary stimuli wasfirst supplied by Sherrington. I He explains that theordinary stimuli are not such as produce visceral painin these conditions and that the stimulus to do somust be of a certain kind-that is to say, it must be anadequate stimulus, a stimulus for which the part ofthe reflex arc concerned has a selective excitability.The adequate stimulus which causes pain is a distensilestimulus, and if the viscus is distended with fluid painresults.The first systematic observations upon this subject

were made by Hurst and his colleagues. 8 Theydistended various parts of the alimentary canal slowlyby the balloon method, and found that at a certainpressure varying in the different regions a sensation offullness and distension was felt by the patient ; if,however, the balloon was rapidly inflated painresulted which was slowly replaced by a sensation offullness, without any accompanying fall in pressure.Thev concluded that there was no essential differencebetween the mode of production of each, and that thecause was tension exerted on the muscular coat,owing to the rise of internal pressure, actual painbeing caused by the rapidity of inflation. I believethat this explanation is correct, and that excessive emuscular tension is the cause of the pain. Theexcessive tension may be due to internal stretching orto muscular contraction. In whichever of these twoways the tension is brought about the effects ofincreased muscular tension are the same, but in itsproduction two different reactions are involved. Ineach reaction the muscular tension is the resultant ofone force due to stretching and another due to muscularcontraction ; but in the one case the primary cause isthe stretching and the tonus reaction a secondaryeffect ; and in the other case the primary cause is theexcessive muscular contraction and the stretching the

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secondary effect of the opposition to contraction bythe pressure exerted upon the gastric contents. It isa well-established fact in physiology that stretchingacts as a stimulus to smooth muscle, and if thestretching is gradual the muscle elongates up to acertain point, when contractions commence ; if rapid,tonic and rhythmic contractions begin at once, butfinally disappear if the stretching process is kept up,as in the distension experiments mentioned just now.The excessive tension is never the result of simplepassive stretching of the muscle, and in both reactions,whether primarily due to stretching or to muscularcontraction, the muscular contraction is really theessential factor and the tension produced in the fibreis an abnormality of the contraction tension. Thecommonest cause of excessive contraction tension indyspepsia is increased contraction of the muscle itselfand not stretching, because pain due to stretching soonpasses off as the muscle accommodates itself. Thestomach may be stretched to enormous limits withoutpain, as in the so-called acute dilatation, which isreally an acute distension with fluid. In atonicconditions of the stomach there is no pain because themuscle-fibre is unable to recover its normal tone.

Payne and Poulton have advanced a theory ofvisceral pain which is opposed to that which attributesit to tension in the muscle-fibre. They found that incases of more or less prolonged pain there was anincrease of the mean pressure within the organ ; thatwhen the pain was momentary it was associated witha single muscular contraction and occurred as themuscle relaxed ; and that a peristaltic contractionrelieved the pain of the distended oesophagus. Theyconcluded that when the wall of an organ is stretchedall the structures forming it, muscle-fibres and nerve-endings, take up the tension and that the pain is dueto stretching of the nerve-endings that subserve thesense of pain. If the muscle contracts it overcomesthe stretch and takes the strain off the nerve-endings,although the tension in the muscle-fibre is furtherincreased bv this act. I find it difficult to see eye toeye with Poulton and to interpret the symptoms ofdyspepsia by this theory, and for the present at allevents must retain the hypothesis that pain is dueto an increase in the contraction tension of the muscle-fibre, which assumption, as we shall see, is rendered allthe more probable, since it enables us to interpret thesymptoms of dyspepsia. Great variations in thecontraction tension of the muscle-fibres do notnormally occur in the alimentary canal, andSherrington 10 has explained why this is the case. Heshows that a muscle may lengthen or shorten withoutappreciably lessening or increasing its contractiontension ; this form of activity he speaks of as postural.It is essential that the stomach should be easily ableto accommodate food received often quickly and inlarge amount without much alteration in its internalpressure, otherwise there would be an obstacle to theentrance of food. The body of the stomach is ableto accommodate itself as it is filled by a lengtheningreaction and similarly as it empties and the contentsdiminish in volume by a shortening reaction. Itassumes different postures to suit the volume of itscontents without increasing the contraction tension ofits muscle-fibres. Similarly, a sphincter which isclosing an orifice is in the condition of posturalcontraction and shows no excess of tension on themuscle-fibres. The excised stomach is able to carryout these reactions although less perfectly than whenit is controlled by the finely adjusted balance betweenits motor and inhibitory nerves. Any interference withthis postural adaptation of the musculature results inan increase in the contraction tension of the fibres anddiscomfort or pain follows. The most important causeof such an interference is irritability of the neuro-muscular mechanism in which state the muscle-fibrereacts too readily and too strongly to stimulation andmay become spasmodically contracted. Repeatedabnormal stimuli give rise to a permanent irritabilityand exhaustion is liable to follow, leading to a conditionof irritable weakness in which the muscle reacts tooreadily, but incompletely. This irritability affects

both the lengthening and the shortening reactions ofthe muscle-fibres-that is to say, produces its effectsduring the filling and the emptying of the stomach.In the former case the muscle refuses to relax in thenormal fashion and in the latter contracts too ener-getically, so that in both cases the internal pressurerises as a secondary effect. When the increased con-traction occurs late in the digestive process as theresult of excessive stimulation by the gastric contents,filling the stomach puts an end to the symptoms byinducing a normal lengthening reaction. If themuscle is initially irritable a normal lengtheningreaction cannot be so well induced by eating andpain occurs as soon as food is taken. Apart from

irritability of the muscle there are two other conditionswhich interfere with the lengthening reaction andproduced symptoms as soon as food is eaten. Thefirst is too rapid filling of the stomach, as in boltingthe food, whereby time is not allowed for the length-ening reaction to occur. The second is diminishedtone in the muscle, which is really a condition ofirritable weakness. When the stomach is too rapidlyfilled the internal pressure acts as a stimulus tocontraction, but in all other conditions this internalpressure is entirely dependent upon the energy ofcontraction. In each case the internal pressureopposes the contraction and thus increases thecontraction tension. Since pain appears so muchmore easily in some individuals than others, or atcertain times more than others in the same individual,the stimulus in each case being of the same degree.-it is clear that some other factor must be involved.and this factor is the degree of sensitiveness of thenervous system, for pain appears more readily inproportion to this sensitiveness.

In the patient with neuropathic tendencies not onlyare the reflex motor disturbances responsible for thesymptoms more easily excited even by a normal orsubnormal stimulus, but their sensory manifestationsare exaggerated. Now a surprisingly large number ofpeople have such tendencies without really deserving-the name of neuropath, and perhaps most patients asthe case progresses show an increasing irritability ofthe nervous system in a manner which will be discussedlater, so that there is no sharp dividing line betweenthe person of average normal stability of nervoussystem and the neuropathic patient. In both the-sensations which are. experienced become exaggeratedin different degrees and more clearly defined in con-sciousness as the result of their prolonged continuanceand the attention paid to them. The parts in whichthis factor plays the most prominent r6le are theoesophagus and body of the stomach, because they aremore closely connected with consciousness than thepyloric end. Certain normal sensations are receivedfrom them which on exaggeration become symptomsof dyspepsia. The act of swallowing can often be feltif the attention be concentrated upon it, particularlyif the bolus be larger than usual. The oesophagus canappreciate heat and cold, and a burning sensation onswallowing concentrated alcohol. Hunger sensations,sometimes amounting to pain, and the pleasurable actof filling the stomach concern the body, which also’experiences a sense of fullness or distension when alarger meal than usual has been eaten, particularly ifswallowed quickly. Voluntary control can be exer-cised over the cardiac end and gas eructated to relievethe pressure within it. On the other hand. the pyloricend gives no sign whatever to the normal individual’that it exists at all. It is only to be expected, therefore,that such sensations should be more easily excited anddevelop into pain with more moderate degrees ofmuscular contraction than are responsible for pain atbhe pyloric end of the stomach.

Local and Referred Pain.We must now turn to a consideration of the question

3,s to how far it is possible to determine with anylegree of certainty by the study of pain whetherhe oesophagus, the cardiac, or the pyloric region of&otilde;he stomach is the part of the apparatus disordered-rhis would be quite a simple procedure if all visceral i

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pain were local-that is to say, situated directly inthe affected part-because it would then be strictlyconfined to the area of the part. This is, however, notthe case, because whenever the contraction tension ofthe muscle oversteps a certain variable limit referredpain appears, which differs from local pain in that itis often felt at a distance from its source and not onlyin front but also behind. The relative importance ofthese two kinds of pain has given rise to considerablediscussion more particularly during the last 40 years,and disagreement still exists ; so that I must nowclearly define my attitude towards this subject.

Local Pain.-The first observer to describe definitelytwo kinds of pain was Ross 11 in 1888, splanchnic, whichwas felt in the organ itself, and somatic, which wasreferred to the wall of the body. Head,12 in 1905,expresses the view that the viscera possess a low formof sensibility called by him protopathic, whereby theycan feel pain and extremes of heat and cold, but thesesensations cannot be accurately localised. Mackenzie, 13on the other hand, denied the existence of local pain.Now there can be no doubt that the minor sensationsfelt in dyspepsia, the feeling of a lump or weight, or ofdistension and fullness, or of hunger sensations, areall local. They are all more or less special sensationsand are merely an exaggeration of the normal feelings,which everyone now and then experiences. They arenever felt in any other position than over the regionof the organ producing them, they are never felt inthe back, they do not radiate, neither are they everaccompanied by reflex phenomena. It is only reason-able to suppose, therefore, that when these sensationsbecome painful the pain may also be local. The

oesophagus localises its sensations fairly accurately,and they are felt in the mid-line of the sternum fromthe root of the neck to the epigastric angle ; this lowerpoint may correspond more or less with the apex ofthe ensiform cartilage or may be below it if thecartilage is very short. The boundary line betweenlocal oesophageal and gastric sensations is naturallyindefinite. Local gastric sensations, whether of fullnessor hunger, are felt diffusely over the upper abdomenbetween the ensiform and the umbilicus and more tothe left than the right. Both these sensations, fullnessand hunger, are particularly concerned with the bodyof the stomach, so that the above area is that inwhich body sensations are felt and they are alwaysdiffuse and badly localised. When actual pain occurslimited to the central line of the chest, or diffuse andindefinite pain limited to the gastric area, such painmay be local. Although we do not seem to benormally conscious of the pyloric end of the stomachor of the pyloric sphincter, it no doubt causes painbadly localised and indistinguishable from that dueto the body.

Referred pain is of much greater importance thanlocal pain, because it is the chief gastric pain, itsposition is localised and constant, and it shouldtherefore be definitely indicative of the part of thestomach affected. References to it are to be found inthe earliest medical literature, and such pains occurringin parts of the body remote from the organ causing themwere known as " sympathetic pains." In later timesdirect anatomical connexions between certain spinaland sympathetic nerves were demonstrated, and it wassupposed that in some way or other nerve impulsespassed from the one to the other ; thus pain occurredin the distribution of the spinal nerves when theanastomosing sympathetic nerves were irritated.No definite explanation, however, was offered as tohow the transmission of the impulse was effected.The first observer to enunciate clearly the principlethat the transmission was effected in the centralnervous system was Dr. S. Martyn, professor of

physiology and physician to the hospital at Bristol. 1-4In 1864, in discussing the origin of chest pain dueto the heart, he writes : " Reflected or radiated painis now recognised as extremely common. In cases ofsensory nerves entering a great centre at the samespot, if the peripheral end of one be irritated, we feelpain in, or refer it also to the periphery of the other."He considered that the impression of some distress in

the heart was received through nerves entering thegrey posterior columns of the spinal cord, and that thecentral impression was irradiated and referred by themind to the sensitive skin. Ross,ll in 1888, in clearlydistinguishing between local and referred pain givesa similar explanation of the latter, for he says thatthe irritation from the splanchnic nerves is conductedby the posterior roots to the grey matter of the posteriorhorns, diffuses to the roots of the correspondingsomatic nerves, and causes an associated pain in theterritory of distribution of these nerves. The par-ticular regions in which oesophageal and gastric painare felt were first described by Mackenzie 13 in 1892.He also drew attention to associated tender points inthe abdominal wall, cutaneous hyperaesthesia, andincreased reflex irritability of the recti. Head,15 in1893, systematically mapped out the areas of cutaneoustenderness, in which referred pain also occurred,corresponding to each segment of the spinal cord.

These observers considered that a focus of irritationis set up in the spinal cord and that sensory impulsesfrom other parts passing into this segment are so

exaggerated as to be painful. According to Headreferred cesophageal pain occurs in the fifth and sixthdorsal areas-that is to say, over the lower part of thesternum and occasionally in the seventh area ; referredgastric pain occurs in the seventh, eighth, and ninthareas, each occupying about a third of the distancefrom the ensiform to the umbilicus from above down,and occasionally in the sixth or tenth area. Behindthe space covered by these areas extends from theninth to the twelfth dorsal spines. He advanced thehypothesis that the seventh area corresponds to thecardiac end and the ninth area to the pyloric end ofthe stomach, but says he has no proof to offer of thissupposition. Mackenzie agrees with Head as to thedistribution of oesophageal pain, but differs as regardsgastric pain, for he limits it to the epigastrium andexcludes the supraumbilical region. Neither of theseobservers supported his contention with a definiteseries of cases, and no useful clinical scheme to assistin diagnosis has since been evolved. Although it isimpossible to say whether oesophageal pain is localor referred unless it extends across beyond the centreof the chest and occurs in the back, in the case of thestomach the very common localised points of pain inthe mid-line and along the costal margins are

undoubtedly of the referred type because each corre-sponds to an area of pain at the back; each oftenspreads out as a band across the abdomen not so muchof pain as of tightness, the patient stating that thefeeling is as if he were encased in plaster or a tightband or gripped by a vice ; each usually shows thepoint of deep tenderness pointed out by Mackenzie,which assists the patient in localising the maximumpoint of pain ; and at some time or other rigidity of theupper recti will be commonly but not necessarily found.It is quite impossible for gastric pain to be so welllocalised and to occur over such a small area in aposition not directly over the stomach unless it is ofthe referred type. All these referred pains occurringin the back result from afferent impulses passing upsympathetic fibres from the muscular coat of theorgans. The afferent impulses from the mucous

nzenabrarae of both stomach and aesophagus pass upthe vagus, so that the local sensations of coldness andburning are accompanied by referred pain in thedistribution of the fifth nerve, upper and lower jaw.forehead and nose, and so on, in accordance with therelation of the tenth to the fifth nerve as pointed outby Gaskell.16 e These local sensations of the mucousmembrane are almost entirely confined to the aeso-phagus. The temperature sensations of the mucousmembrane of the cesophagus are of very little import-ance in clinical medicine, but the burning and stingingsensation, popularly known as heartburn, is commonenough. It is felt beneath the lower sternum and maybe reproduced in the normal individual by swallowingconcentrated alcohol, but as Hurst 8 has shownhydrochloric acid of the highest strength found in thehuman stomach is unable to produce this sensation inthe r ormal person. Heartburn cannot be due to the

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formation of alcohol or other fermentation productsin the stomach, because such a condition is practicallyunknown in functional disorder. It is chiefly seenin cases of so-called hyperchlorhydria, but it is acommon experience that, although regurgitation ofthe highly acid gastric contents is common in thiscondition, the fauces are usually irritated and not theoesophagus. It must be remembered, however, thatregurgitated gastric contents may be retained in thelower oesophagus for some time, which is quite adifferent matter from a momentary contact with themucous membrane. Furthermore, in neurotic patientsa sensation of soreness or burning may occasionally befelt in the whole oesophagus on swallowing food. Thisis due to hypersensitiveness of the mucous membranewithout a doubt and of the same nature as heartburn.It is therefore probable that when the nerves of theae30phageal mucous membrane become hypersensitiveHCI is able to produce heartburn. Sometimes heart-burn is associated with severe pain, due to muscularspasm. The chief sensation from the mucous

membrane of the stomach is a slight tingling or

burning when alcohol is taken, and it is likely that theburning and soreness complained of by neuroticsubjects in the epigastrium is due to hypersensitivenessof this structure.In stating the relative importance of local and

referred pain in the diagnosis of the part of theapparatus affected, one may say that in the case ofthe oesophagus they are of equal usefulness, becauseeach can be localised equally well and they can onlybe distinguished by the occurrence of pain towardsthe sides and back. It is a different matter with regardto the stomach, for, although both types of pain occurin the same region, local pain is too indefinite to be of Imuch value as an index of the part affected ; on theother hand referred pain, being localised usually to smallareas and constant in position, is clearly indicative ofthe part of the stomach affected. The cases which Ishall now describe are not selected, but are takenfrom my case-books over a series of years in the orderin which they occurred in my practice, and form arandom series such as appears before every physician,except that the examples of structural deformity whichwould occur in such a series have been excluded.

ANALYSIS OF CASES : PAIN.

The most important symptom to be considered ispain in all its varieties. The first point to be deter-mined is whether the position of the pain is a definiteindication of the part of the apparatus causing it.The pain areas mapped out by Head are areas ofcutaneous hyperaesthesia, which can be marked outfairly accurately. The subjective sensation of paincannot, however, be outlined in a similar way, unlessit is localised to quite a small area. Now I have foundthe areas of cutaneous hyperassthesia to be of verysmall value in diagnosis as a general rule, because theyare so uncertain and irregular in occurrence, althoughnow and then one or more complete areas may bemarked out. The idea of describing segmental areas ofpain had, therefore, to be abandoned as impracticable.The main division into oesophageal and gastric areaspresents no difficulty, for the former is the sternalregion extending from the root of the neck to andincluding the apex of the epigastrium ; and the latterincludes the region below this to the umbilicus. Thesternal region appears to be divisible into two parts,an upper and a lower, separated at about the level ofthe fourth costal cartilage. Referred pain is veryfrequent in the lower area, but much less common inthe upper, although it occurs at times in this position :it does not seem to appear above the second costalcartilage (Fig. 1). The region between the sternumand the umbilicus presents the difficulty that it hasno name. From the point of view of referred pain the ]usual areas into which the abdomen is divided are of 1little use, however serviceable they may be in other ]respects. The body wall is segmented into areas 1

corresponding to the segments of the spinal cord and 1irrespective of the positions of the underlying organs. <

The part which concerns us-namely, that above the f

s level of the umbilicus-differs markedly from the partT below in regard to segmentation. 1ot only is referred1 pain more frequent and more clearly defined in this1 position, but its anatomical segmentation as shownf by nerves and tendinous intersections is more clearlys marked out. This part above the umbilicus is differ-3 entiated before the eighth week of foetal life ; but theb lower part is only completed at the end of the twelfth3 week after the return of the intestine from the extra-L I embryonic coelom to the abdominal cavity, to which itslate development is probably due (Harris).17 Thes anterior body wall is thus naturally divided at the

Central positions of referred pain in each of the anterior regions

umbilical level into supra- and infra-umbilical parts.I propose, for purposes of description, to call the upperpart the sterno-umbilical region. At first sight itseems impossible to distinguish different areas of painin such a small region, but it can be done with sufficientaccuracy for our purpose by dealing with a largenumber of cases to eliminate errors, particularly asthe areas of referred pain are very commonly no largerthan the size of a half-crown piece. It must furtherbe remembered that this region presents the greatestdifficulties in diagnosis of any other region of the body,since the pain felt here may be due to almost anyorgan of the chest or abdomen, in addition to a greatvariety of other causes. From the point of view ofthe alimentary canal the lower part of the region ismore difficult in this respect than the upper, for itrepresents both the intestines and the biliary apparatusequally with the stomach. The transpyloric plane cutsthe mid-line of this region exactly at its central pointand divides it into upper and lower parts. It is usuallyeasy to determine whether the patient points above orbelow this line to indicate the position of his pain, andhe very commonly touches the central point of theline itself-so that the sterno-umbilical region may bethus divided into three parts, an upper, middle, andlower. The position of the pain, whether a small orlarge area or a band, was marked out on a diagram atthe time of examination in every case. The positionof the small areas was mostly on the mid-line except inthe lower part, in which they were situated quite asoften towards one or other side, especially the right.By adopting this method in a sufficiently large numberof patients, the error, which in any case must beconsiderable, was reduced as much as possible.

There are 1009 cases in all, of whom 715 exhibitedpain in one area and 294 in multiple areas. Thedistribution of pain in 624 of the 715 cases is asfollows :-Sternal region .. , , , ,

upper 53 cases.bternai region ...... lower ....119"

... upper 223 "

Sterno-umbilical region middle o : e 152 lower .... 77 "

If these areas really represent the different parts)f the oesophagus and stomach from above down, theJain occurring in each position should have a definiteime relation to the intake of food depending upon the)art affected and the mechanism put out of gear,because the symptoms appear when the apparatus is atvork and cease when it is at rest. That pain occurs atUfferent periods of digestion is a very old-establishedact, and the replies which patients make to this

1164

question may be divided into four groups..(1) Atonce or within a few minutes of eating. (2) Half toone hour after food. (3) One hour or more up toseven after food, in which case the patient feels it inthe early hours of the morning. (4) Irregularly, thatis to say, the symptoms have no clear relation to meals,or are always present to some extent.By adopting this grouping the time relation to the

taking of food in the case of each area is as follows :-

With regard to the time of onset it therefore seemsclear that the higher up the pain is situated the earlierit appears during the digestive process. The exactpercentages are as follows :--

Symptoms appearing-

At once or From 1 hr.thereabouts. upwards.

Per cent. Per cent.of cases. of cases.

Upper sternum ...... 66-6 ...... 12’5Lower sternum .... 30-1 ...... 38-4Upper st.-umb. 27-8 ...... 47-3Middle st.-umb. 12-8 ...... 74-4Lower st.-umb....... 2-7 ...... 90&deg;1

The mechanism of the stomach is likely to be upsetat the time when it is subjected to the greatest stress.The part concerned with the filling of the stomach-namely, the oesophagus and body-is likely to beaffected in the earliest stage ; but that concerned withthe emptying of the organ-namely, the body andpylorus at some later stage, when the contents havebecome irritating, since the more digestible parts leavethe stomach first and the acidity is continually rising.So that early pain situated at the highest level shouldindicate disordered action of the oesophagus and latepain at the lowest level disturbance of the pylorus ;whilst symptoms situated at an intermediate positionand occurring both early and late should indicate adisorder of the mechanism of the body. The above

R g u r e s must un-doubtedly be inter-preted in this way.The oesophagus andbody meet at theintermediate posi-tion and the cardiacsphincter of thestomach is in factthe lowest part ofthe oesophagus,h e n c e symptomsreferring to the loweroesophagus shouldpartake of the natureof both oesophagealand body symptoms.This appears to bethe case, since thetime of onset of

symptoms in these two parts correspond very Iclosely. Although these two parts must overlapit is probable that an isolated pain below the Iensiform usually refers to the body of the stomach,for cases occur in which this pain is followed in ashort time by a band of pain across the ensiformand lower sternum, or in which this pain is associatedwith paroxysms of pain over the ensiform (Fig. 2).Furthermore we shall see later that the relation ofeach of these areas to the feeling of fullness is different.It is certainly justifiable to draw the following con-clusions (Fig. 3). (1) Pain occurring in the uppersternal region usually comes on either at once afterfood or irregularly and is associated with disorderedaction of the upper oesophagus. (2) In the lower

sternal region it is particularly associated with disorderof the lower part of the oesophagus and appears atonce after food or irregularly, but quite as often fromone-half to two hours after food. (3) In the uppersterno-umbilical region it indicates disorder of thebody of the stomach and appears also at once orirregularly, but rather more often from one-half totwo hours after food; the two latter regionsindefinitely pass into each other. (4) In the middleand lower sterno-umbilical regions pain indicatesderangement of the pylorus and commonly appears

Pain region corresponding to each part of the oesophagusand stomach.

more than two hours after food. The middle regionshows an appreciable number of cases of pain at onceor irregularly, and this region therefore to someextent represents the body of the stomach althoughit chiefly refers to the pylorus.A further analysis of the one to two hours’ pain

shows that in the case of the body more cases showpain in this period than later and in the case of thepylorus the reverse is the case

The following analysis of 361 cases was made :-

Pyloric pain, therefore, is more likely than not toappear later than two hours after food.The part of the, apparatus and the mechanism

affected is not the only factor which determines theearly or late onset of pain, and we must now considera feature of gastric pain which suggests this to bethe case. This character is a tendency for the pain toshift forwards as the case proceeds on its course and toappear sooner after a meal than it did before. This is,of course, most noticeable by the patient in cases inwhich the pain initially appears late during digestion,but occurs in any type of case and in all positions ofpain. The patient, for example, says that the painused to start half an hour or two hours after food,but now it comes on at once after eating. Sometimeswhen the pain is moderate in degree it starts late afterfood, but when very severe it appears at once.

Sixteen of the 77 cases of lower sterno-umbilical painshowed this latter feature. The tendency is thereforefor any of these pains to become constant, food notaffording relief as before and the patient only beingfree from symptoms first thing in the morning whenhis stomach is empty. The pain may then come onearly or late after breakfast and remain constant forthe rest of the day. In some cases when the painappears early from the beginning it may ’disappearbefore the next meal, but eventually tends to becomeconstant like the late pain. All cases do not behavein this manner and many preserve their initial timerelation to food for considerable periods, more particu-larly pyloric cases. The suggestion is that there issome definite cause for this, sometimes operative andsometimes not. It cannot result from retention of the

1165

stomach contents, because, if this were due tosecondary atony and diminished peristalsis, any paincaused by the body of the stomach would be lessened ;and, if it were due to holding up by the pylorus, thiswould indicate an increased irritability of the sphincteras the actual cause. It is, in fact, an increasedirritability of the neuro-muscular mechanism of thestomach which is the cause. The normal muscular

response of the stomach to the presence of food

depends upon a nervous reflex, and with constantirritation this responds more easily, and eventually thejnere presence of food,however mild, will excite theabnormal movements responsible for the symptoms.This increased reflex response to repeated stimulationis in accordance with a general physiological law andexhaustion is liable to follow eventually, some degreeof atony supervening, unless the disorder is put anend to. The central nervous system also becomesirritable and affects the stomach through its extrinsicnerves. This increasing irritability of the nervousmechanism is shown in several other ways. Theattacks of dyspepsia tend to become more frequentand prolonged and the symptoms more pronounced incharacter, although there is no obvious cause to befound except exhaustion or nerve strain. At firstdiminishing the stimulus by cutting off variousarticles of food brings relief, but later even the mildestfood causes pain, and vomiting starts in bad cases;that is to say, a subnormal stimulus causes an

abnormally excessive response. In addition toincreased reflex irritability of the neuro-muscularmechanism, hyperaesthesia, as I have already stated,occurs. The attention tends to be more and more fixedupon the symptoms, so that they become more clearlyperceptible and exaggerated in consciousness. Theideas the patient forms about his symptoms worry him,and more particularly the idea of serious disease,especially cancer. He imagines that first one foodstuffand then another disagrees with him, and his dietbecomes correspondingly restricted. He gathersadvice from his friends and the newspapers and triesall kinds of medicines. The symptoms are affectedby emotional disturbance and overwork. All theseresults depend upon one thing only, and that is thedegree of stability or irritability of the nervous systemof the individual concerned. They occur in varyingdegrees in most cases of prolonged dyspepsia whatever I

the type, but are more likely to appear and to beespecially pronounced in affections of the oesophagusand body than the pyloric region of the stomach.’The oesophagus and body of the stomach, therefore,are liable to develop early and constant pain not onlyin virtue of their position and functions, but also invirtue of their being already better represented in thecentral nervous system and more subject to itsinfluence.A consideration of irregular pain tends to confirm

this hypothesis. Here again we find that the uppersterno-umbilical region and sternum are more liableto this type of pain than the regions below. Therfollowing percentages prove this point :-

The oesophagus and body of the stomach are there-fore more liable to irregular pain than the pyloricregion. By carefully questioning the patient one canmore or less map out this irregular type into threechief groups : (1) The pain occurs either early or lateafter food. (2) At any time by day or night. (3) Con-stantly, even when the stomach is presumably emptybefore breakfast. The first group is fairly equallydistributed between the cardiac and pyloric ends andappears, at all events, sometimes to depend on theparticular meal eaten ; for example, it may appearsoon after a small meal and late after a heavy meal ;or soon after some particular meal-for instance, tea-- and late after the others ; or it may come on early I

if he is worried or tired. The second group in whichpain comes on at any time is certainly more likely toaffect the body and oesophagus. It is often referredto a cause such as straining movements too soon aftermeals, stooping to work, sitting in a cramped position,being shaken up in a car or train, lying down at dayor night, and above all emotional disturbance. Manyof these are the result of increased pressure upon anirritable stomach, or the horizontal position, whichinduces oesophageal symptoms by regurgitation. Thethird group of constant pain is certainly more

particularly characteristic of a high degree of nervousirritability of the stomach and more particularlyaffects the oesophagus and body.

It may be stated generally that pain appearing atonce or within a few minutes of a meal. or occurringat any time. or constantly is characteristic of excessivenervous irritability of the stomach. There are fourfurther points with regard to pain .which are of someinterest and importance. The first is the severity ofpain in different positions. The two places where themost severe pain is felt are those adjacent to eithersphincter, because the contraction tension of themuscule fibres is better opposed in those situations,and spasm is likely to occur. In the upper oesophagusand body of the stomach the pain is more moderate indegree and most often one of the minor sensations.Secondly, paroxysmal pain may occur in quite anirregular fashion at either sphincter, more particularlyat the cardia. The patient is usually the subject ofdyspepsia, but may have no other symptoms, inwhich case it is probably of reflex origin. Thirdly,symptoms may occur during the night and wake thepatient. Any part of the stomach or oesophagus maybe responsible for this, and it is due to three causes.

1. It is the variety of pain which comes on late duringdigestion and then is most often pyloric in type. It merelymeans that the pain is a severe pain, and it must beremembered that some individuals wake much more easilythan others. However, the more severe and regular thepain the more likely it is to be due to organic disease,although pain due to simple functional disturbance notuncommonly wakes the patient.

2. The cause may be regurgitation into the oesophagus ofthe gastric contents owing to the position of the patientand the respiratory alterations of pressure in the stomachand oesophagus. Such a patient may wake with what hecalls heartburn, or waterbrash, or a coughing attack due toregurgitation of gastric contents which irritate the larynxand which may also so irritate the fauces as to make himvomit. In each case he may complain of waking with apain or curious feeling in the epigastrium in the first instanceor not.

3. He may wake with a feeling of great distension, whichleads to an attack of nervous eructation. In short, anysevere symptom may wake the patient.

Finally, in patients with chronic dyspepsia periods ofrelative or absolute freedom from pain occur fromtime to time, and they are also seen when the minorsensations alone constitute the symptoms. Whetherthe patient is suffering from an organic lesion or

simple functional disturbance makes no matter. Thefree intervals are due to treatment or they are due tore-establishment of the normal stability of the nervoussystem by rest, holidays, and the like. This appliesto patients whether the disorder is painful or not, butif painful it is more noticeable, since they are morelikely to take definite steps to get rid of the disorder.Perhaps it may be stated that severe pain recurringover a series of years in the male sex is most likely tobe due to an organic lesion, and that patients sufferingfrom minor sensations affecting the body and

oesophagus are more likely than any other class to sufferfrom more or less constant symptoms without muchfreedom.Pain ira the Back.-The areas given are only approximate,

since there is often great difficulty in localising the pain.Each pain area in front has a corresponding position forpain behind. Pain in the back does not occur in all cases?f referred pain and never appears alone without pain in theEront being felt at some period of the disorder. The areasue usually more extensive and indefinite than the anteriorueas though not necessarily so. The pain may be situatedn the centre over the spine, across both sides of the back,3r more usually on the left side only. Sometimes the areas

1166

are small and appear on the left of the spine in a line withthe angle of the scapula. The two pains, front and back,may appear to be separate although occurring together, orthe pain in front may seem to go right through the bodyor round the side to the back. The pain is described asbeing more or less at the same level in the back as thefront, or higher up, but not usually lower down. Of 137 casesof pain in the back 81 corresponded to single areas in frontand 56 to other points or combined areas. The 81 cases

Posterior regions of referred pain corresponding to theanterior regions.

are considered here-namely, those associated with theanterior areas described above. The levels varied a littlein different cases, so that the highest and lowest points ineach area were noted and the region included between theselevels is described as that corresponding to the anteriorarea (Fig. 4).

Lower Sterno-umbilical Area.-The lowest point of

posterior pain was at about the level of the second lumbarspine. In 13 out of 14 cases the highest point reached toabout the tenth dorsal spine and in one to the eighth.

Middle Sterno-umbilical Area.-The lowest point was

about the level of the twelfth dorsal spine. In 11 cases thehighest point reached to about-the seventh or eighth dorsalspine.

Upper Sterno-umbilical Area.-The lowest point was aboutthe level of the tenth dorsal spine. Nineteen out of 26 caseshad pain as high as the seventh or eighth dorsal spine and7 as high as the sixth.Lower Sternal Area.-The lowest point was about the

eighth dorsal spine. Sixteen patients complained of pain

Pain region corresponding to each part of the oesophagusand stomach.

as high as the fourth dorsal spine and five as high as thethird.

Upper Sternal Area.-The lowest point was about thesixth dorsal spine. Nine patients complained of pain as highas the second dorsal spine.

Expressing these areas in terms of the differentparts of the stomach the following result is obtained(Fig. 5) :-

Pyloric Region.-This part may be associated withposterior pain from about the eighth dorsal to the secondlumbar spine ; that is to say, the pain may reach upwardslaterally to about the angle of the scapula.

Cardiac -Rcf/tOM.&mdash;The posterior pain associated with thisregion of the stomach may extend from about the sixth tothe tenth dorsal spine; that is to say, opposite the lowerthird of the scapula and for some distance below.

(E’sopa/MS.&mdash;The upper part shows posterior painopposite about the upper two-thirds of the scapula and thelower part shows pain opposite about the lower two-thirds.

These are the limits of the pain more or less, but it.is not as a rule so extensive in any individual case ;the area may be quite a small one, or the patient maymove the back of his hand up and down over theposition in an indefinite manner, or draw his handacross the back to signify the position of the pain.

Radiation of Pain.-In most cases the pain remains:localised to the positions described above, butsometimes it radiates in different directions and maybe described by the patient as being " like knives."

1. The commonest type is radiation from the front to thepositions described at the back. In this type the radiationis usually limited to the particular segment of the spinalcord affected.

2. In another type the radiation affects several segmentsand in the majority of cases passes upwards from the partaffected. It may radiate from any part. It shoots up thecentre of the chest or to one or both nipples, more often to.the left, or up the costal margin, or up the back. Occasionallythe pain shoots downwards ; if it is affecting the upper-sterno-umbilical area and ensiform cartilage it may shootdown the costal margins or vertically down the centretowards the umbilicus. It is rare for it to invade any segmentbelow the ninth dorsal. In other words, it remains limitedto the segments of the spinal cord connected directly with.the oesophagus and stomach. Sometimes in a very neurotic

patient it may be described as spreading into the limbs.

Lateral positions of referred pain in each of theanterior regions

the resistance to spread in the central nervous system beingbroken down.

3. Combinations of these radiations are also found bothhorizontally, and upwards, or downwards. For example,from the lower sterno-umbilical area it may radiate roundthe sides, through to the back and also up the chest ; fromthe upper area it may radiate up the sternum and downboth costal margins ; from the lower costal margin it mayradiate horizontally and up the costal margin or to the leftnipple ; and occasionally upwards, downwards, and hori-zontally like the spokes of a wheel.

This radiation is of no significance except that it definitelypoints to the stomach as the organ affected in doubtfulcases, and the position from which it radiates indicates themost irritable part of the stomach.

Continuing the description of the cases, we havenow to consider the remaining 91 cases of localisedpoints of pain ; 81 of these occurred at the costalmargins and 10 in the region of the nipples. They are-oc follows (Fig R B

The most important positions are the lower partsopposite the ninth costal cartilage. These points lie.on the transpyloric plane, where it cuts the costalmargins. The size of these areas varies ; sometimesthey are quite small or they spread out indefinitelyup the costal margin and on to the ribs with thispoint as the centre. There is no doubt that they areparticularly connected with the pyloric region of the-stomach, and it is quite common for patients toindicate a line of pain passing through the middle orlower sterno-umbilical region and reaching to the sidesthrough these points. The points of pain near the-nipples are quite localised and on the left side usually

1167

and the patient on being asked to point to the painputs one or two fingers at the nipple or just above orbelow this point. The following tables show the time relations of the

pain in these different positions in relation to meals.

Costal Margin.

Now it is quite clear that the right 9 c.c. area hasthe same time relation to food as the lower sterno-umbilical area : the left 9 c.c. area, and the left andright combined, are similar though not quite so

marked. These two areas, then, should be regardedas indicating pyloric pain as already stated. On theother hand, the left upper costal margin shows thesame characters as the upper sterno-umbilical areaand no doubt represents the body of the stomach.This inference might have been drawn since theirlevels fall within the areas indicating these two regionsof the stomach. I may mention here in support ofthis conclusion that the right 9 c.c. area is a frequentposition of pain in duodenal ulcer and the combinedright and left 9 c.c. areas also, but less frequently.The right upper costal margin is usually combinedwith the lower portion or occurs as a part of pain inthe upper epigastric angle. The position of the painin the nipple region indicates that it is of cesophagealorigin, and so far as this small number of cases goesit supports this conclusion, since the cases showingpain quite soon after food and irregularly are four timesas numerous as the cases occurring in the periodone hour and upwards.The posterior pain associated with these positions is

in agreement with these conclusions.Lozcer Costal Margin.-The position of the posterior pain

varied between the eighth dorsal and the first lumbar spine,which is that of pain associated with the pyloric region.The right costal margin pain is often associated with leftposterior pain.

Left Upper Costal Margin.-The posterior pain occurredfrom the eighth to the tenth dorsal spine, a characteristic ofpain due to the cardiac region.

Inframammary.&mdash;The pain corresponding to this positionoccurred between the fifth and eighth dorsal spines, a

characteristic of the lower oesophagus.Pain above the Nipples.-In one case the posterior pain

was felt in the region of the third dorsal spine, a characteristicof the upper &oelig;sophagus.

Combining the 715 cases of isolated positions ofpain, 182 represent the oesophagus, 249 the body ofthe stomach, and 284 the pyloric end. This gives thefollowing percentages :-(Esophagus 182 = 25.3 per cent.Cardiac end...... 249 = 33-4 "

Pyloric end...... 284 = 39-7 ,.

It is obvious that these areas of pain in the line ofthe nipple and in the costal margin have precisely thesame meaning as the central points at about the samelevel. It thus appears that there are three lines oflocalised pains : the first down the centre, the secondin the line of the nipples and the costal margin, andthe third more or less in the centre at the back or tothe left of this in the line of the scapular angle. .

Tenderness and Rigidity.&mdash;The most important. of these reflex phenomena, because the most constant, are the deep tender points described by Mackenzie andthe muscular rigidity. The cutaneous tenderness described by Mackenzie and Head, as I have already stated, I have found to be so uncertain and irregular in its appearance and so temporary that it is of little 6practical use in diagnosis except on occasion. Thesephenomena which occur with referred pain and depend IUpon the same mechanism for their production are most

obvious when the pain is at its maximum. Theygenerally outlast the pain and are present between theindividual attacks of pain, finally disappearing moreor less slowly when a pain period is ended. The reasonfor this is that the gastric irritability causing the paindoes not at once disappear when the pain is relieved,as shown by the great tendency for the pain to recur,unless the treatment is continued for some time. Themost marked instances occur in ulcer of the stomachand duodenum, and in the neurotic patient. In thelatter case a spread of irritation occurs to adjoiningsegments of the spinal cord and the whole abdomenmay be tender and rigid. Such cases are examplesamongst other types of what has been well describedby Hutchison as the chronic abdomen. An increasedreflex contraction of one or other rectus has the

same meaning, and as Mackenzie pointed out whenit is present the reflex may be obtained from the skinin the axilla even up to its summit. The deep tenderpoints are usual occurrences with referred pain of anydegree of severity. They are felt in the abdominalwall and less commonly in other positions, andcorrespond in position with the painful pointsdescribed above. They are a good guide to thelocalisation of the actual position of the maximum pain.They are much less common at the back. They arethus of great importance in that they are an objectiveindication of the part of the stomach affected.The rigidity affects the upper segments of both recti

or one only. It is to some extent an indication of whatpart of the stomach is affected. For example, in aseries of 75 cases pyloric pain was associated with arigid right rectus in 68 per cent. of cases and withrigidity of both recti in 32 per cent., and body painwith rigidity of both recti in 64 per cent. and with arigid right rectus in 36 per cent. of cases. Rigidity ofthe left rectus without any increased tension at all inthe right does not appear to be common.The main conclusions so far drawn from the study of

this series of cases may be summarised as follows.1. There is no difference between the minor sensa-

tions and pain as regards their significance ; the onemerges into the other, and they are both due toabnormal contraction tension of the muscle-fibre.

2. The position of the pain and the time of its onsetafter eating definitely indicate the part of the apparatusaffected and the mechanism disordered (Figs. 3 and 5).

3. Pyloric pain occurs in the following positions :Across the abdomen in the transpyloric line as a band.or as a localised area in the centre, or at one or bothends of this line where it cuts the costal margin(9 c.c.). Across the abdomen between the transpyloricline and the umbilicus as a band or an isolated area inthe centre, but quite as frequently to one or otherside, particularly the right. Behind the area whichmay be covered extends from about the eighth dorsalbo the second lumbar spine. The pain characteristicallyoccurs late during the digestive process.

4. Body and Lower &OElig;sophagus.&mdash;The pain occurs atsome position between the transpyloric line and theine of the fourth costal cartilage, as a band or localisedrea in the centre or to one side, particularly in thelipple line or along the upper costal margin. Painbetween the transpyloric line and the ensiformlefinitely indicates the body of the stomach and above;his the lower oesophagus, but oesophageal pain mayncroach on the stomach area to some extent. Behind.he painful area may occur opposite the lower two-hirds of the scapula and down to about the tenthlorsal spine. In the case of the body of the stomachhe pain occurs either in the early stage of digestion,r irregularly, or in the later stages, although not sote as pyloric pain ; but oesophageal pain is lessikely to occur late than early or irregularly.

5. The upper &oelig;sophagus is associated with painbove the fourth costal cartilage in front, usually inhe centre, and sometimes opposite the upper two-hirds of the scapula behind. It nearly always occurson after food or irregularly.6. The &oelig;sophagus and body of the stomach are the

arts most likely to be affected in the neuropathicatient.

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7. As the malady progresses most cases tend toshow an increasing irritability of the nervous system, sothat there is no sharp line of demarcation separatingdyspepsia in the individual of average nervous

stability from that in the neuropathic patient.

References.1. Galen : De symptomatum differentiis, Liber unus, cap. iv.,

p. 24 (Froben Press, 1561).2. Bonetus : Polyalthes sive, Thesaurus medico-practicus,

Tomus secondus, lib. iv., cap. xvi., p. 396, 1693.Riverius : Opera Medica Universa II. Praxeos Medica,lib. ix., cap. v., p. 278, 1679. Menjotius : Dissertationumpathologicarum, p. 604, 1665.

3. Cullen : First lines of the practice of physic., 4th ed., 1784,vol. iii., part II., Book II., chap. ii., p. 217.

4. Andrea and others : Dictionaire de M&eacute;decine et de Chirurgie,1837, i., 764.

5. Brinton : Lectures on the Diseases of the Stomach, 2nd ed.,1864, p. 304.

6. Lennander, K. G.: Centralb. f. Chirurg., 1901, xxviii., 209.7. Sherrington, Charles : The Integrative Action of the Nervous

System, 1906, p. 12.8. Hurst, A. F. : Goulstonian Lectures, R.C.P., THE LANCET,

1911, i.. 1051, 1119, 1187, 1215.9. Payne, W. W., and Poulton, E. P. : Quart. Jour. of Med.,

1923, xvii., 53 ; and Jour. of Physiology, 1927, lxiii., 217.10. Sherrington, C. : Brain. 1915, xxxviii., 220.11. Ross, I. : Brain, 1888, x., 333.12. Head, Henry, Rivers, W. H., and Sherren, James : Brain,

1905. xxviii., 99.13. Mackenzie, I. : Med. Chronicle, 1892, xvi., 293 ; Brain,

1893, xvi., 321 ; Symptoms and their Interpretation, 1920.14. Martyn, S. : Brit. Med. Jour., 1864, ii., 296.15. Head, H. : Brain, 1893, xvi., 1.16. Gaskell, W. H. : Jour. of Physiology, 1886, vii., 1.17. Harris, H. A. : Archives of Surgery, 1926, xiii., 644.

THE RELATION OF THE

ANTERIOR LOBE OF THE PITUITARY

TO THE REPRODUCTIVE ORGANS.

BY C. W. BELLERBY, M.A.

(From the Biochemical Department, Middlesex Hospital,London.)

IT has long been known that disease of the pituitarybody has a marked influence on the activity anddevelopment of ’the reproductive organs.

In 1901, Frohlich,l in describing the condition nowknown as dystrophia adiposo-genitalis, showed thatin addition to obesity and lack of growth there wasmarked atrophy of the genitalia. Cushing 2 andothers confirmed his findings, and a large amount ofclinical data has accumulated describing the disturb-ances of sexual function associated with pituitarydisorders. It is of interest to note that, although therehas been some difference of opinion as to othersymptoms produced by pituitary disease, there ismore or less general agreement as to the effect on theorgans of reproduction. As to which part of the’gland is responsible has been the subject of contro-versy, but experimental work has now proved theanterior lobe to be the responsible factor. Considera-tions of space do not allow of an analysis of theclinical evidence, but. in short, it can be said thathypo- or hyper-secretion of the anterior lobe of thepituitary leads to more or less corresponding hypo-or hyper-activity of the ovaries and testes respectively,the consequent effects of which are manifested bysymptoms which vary according as to whether thecondition of hypo- or hyper-pituitarism arises beforeor after puberty.

Experimental Production of Hypopituitarism.It was not until Paulesco 3 devised his operative

technique that any real advance was made in theexperimental study of the function of the anteriorlobe, previous work being of such a nature that littlereliance could be placed on the results. Paulescowas the first to show that, whereas no symptoms wereproduced by removal of the posterior lobe. partialremoval of the anterior lobe resulted in adiposity.

It was left, however. to Cushing 2 and his co-workersto recognise that the condition produced in full-grownanimals by partial removal of the anterior lobe was

identical with the pathological condition, dystrophia-adiposo-genitalis. In addition to adiposity there waspronounced atrophy of the uterus, but whilst folliclesdisappeared from the ovary there was persistence of’the interstitial cells. Furthermore, partial removalcarried out in young animals resulted in a persistentinfantile condition of the reproductive organs,Similar results have been obtained by Aschner,]4Biedl,5 Dott,6 and Blair Bell.’ 7 The last observerfound that there was not only well-marked atrophyof the uterus-both of the muscular coats and of theendometrium-and degeneration of the Graafianfollicles, but total disappearance of the ovarian inter-stitial’ cells. Blair Bell also observed that separationor clamping of the infundibular stalk was even

more effective in causing uterine and ovarian atrophythan partial removal of the anterior lobe. RecentlySmith 8 has succeeded in restoring to normal conditionthe degenerated sexual organs of hypophysectomisedrats by grafting into them portions of the glandsThe results of these investigators not only proved theendocrine nature of the anterior lobe of the pituitary,but also showed the development and activity of thereproductive organs to be dependent upon its secretion.

Experimental Production of Hyperpituitarism.In the past investigators have studied mostly

the condition of hypopituitarism following partialremoval of the anterior lobe, but recently attentionhas been paid to the effects of injection of extractsor the grafting of anterior lobe as a means of produc-tion of anterior lobe hypersecretion. Although various’reports of the effects of anterior lobe extracts havebeen made the first definite evidence of activity wasobtained by Long and Evans,9 who showed that the-daily injection of extracts of the gland into femalerats caused the immediate cessation of the normaloestrous cycle. the cycle remaining in abeyance duringthe period of the injections. Examination of theovaries of these animals killed during the inhibitionperiod showed them to be full of substantial corporalutea. Long and Evans concluded that their extractswere not only toxic to developing ova, but also had astimulating effect on the growth of luteal tissue.This was substantiated by Teel,lo who proved thatthe corpora lutea were functional in so far as sensi-tisation of the uterus was concerned, since injuryto the uterus was followed by the formation ofplacentoma. ,

In contrast to the above results has been the workof Zondek and Ascheim 11 and Smith 12 who showedthat full oestrus can be produced in three-weeks’ old:mice and rats by grafting into them portions of anteriorlobe. Zondek and Ascheim 13 were also able toproduce the same effects by injection of extracts ofthe gland. Brouha and Simmonet 14 reported similarfindings, though they give no details of the method ofpreparation of their extracts. These observationsshow that a substance is elaborated by the anteriorlobe of the pituitary which stimulates the formationof functional corpora lutea in the ovaries of normalmature animals and has also a marked effect on theimmature ovary, causing it within a few days toattain a state of functional activity which it wouldnot reach normally for some weeks.

Scope of Present Investigations.During the past year investigations have been

carried out in this laboratory, and the main principlesrecorded by Long and Evans and Teel have beenconfirmed. It was found, however, that the inhibitionof. cestrus is not dependent upon the daily injection ofextracts, since inhibition periods of two to three weekscould be obtained by the single injection of 1.0 c.cm.or less of certain extracts. The end of the inhibitionperiod is indicated in many cases by bleeding fromthe vagina. These results are in accord with theobservations made by Teel 10 on the formation offunctional corpora lutea, since the inhibition periodsfollowing injection are, on the average, of the samelength as those which follow from mechanical stimula-tion of the cervix of the uterus. Potent extracts can