'Ttt)i QU Digitized by the Internet Archive in 2010 with funding from Open Knowledge Commons http://www.archive.org/details/arterialhypertonOOruss ARTERIAL HYPERTONUS, SCLEROSIS AKD BLOOD-PRESSURE ARTERIAL HYPERTONUS, SCLEROSIS AND BLOOD-PRESSURE WILLIAM RUSSELL, M.D., F.R.C.P., Edin. PHYSICIAN TO, AND LECTURER ON CLINICAL MEDICINE IN, THE ROYAL INFIRMARY, EDINBURGH ; LECTURER ON PRACTICE OF MEDICINE, FORMERLY LECTURER ON PATHOLOGY^., SCHOOL OF MEDICINE, EDINBURGH WITH THIRTY-SIX ILLUSTRATIONS AND PLATES PHILADELPHIA J. B. LIPPINCOTT COMPANY EDmBURGH: WILLIAM GEEEN & SONS 1908 CONTEXTS CHAPTER I THE NORMAL STRUCTURE AXD ilOVElIENTS OF ARTERIES PAGE Structure — Tone — Movements — Pulsatile Movement — Tonus and Hypertonus ....... 1 CHAPTER II BLOOD-PRESSURE AXD ITS RELATION TO VESSEL CONTRACTION AND HEART POWER Blood-Pressure — Determining Factors— Measurement of — Physical Facts regarding — Effect of Peripheral Constriction on Blood - Pressure — Effect of Peripheral Constriction on the Heart CHAPTER III DISEASES OF ARTERIES Introductory — Historical Summary — Relation of Atheroma to Arterio-sclerosis — Arteries and Heart in Granular Kidney — Atheroma and Endarteritis Deformans — Etiology — Obliterative Endarteritis and Acute Aortitis — Arterio-sclerosis — Changes in Arteries of the Kidney in Arterio-sclerosis, " Arterio-capillaiy Fibrosis"— "Hypermyotroj)hy" — Conclusion . . .13 CHAPTER IV HYPERTONUS AND ITS CLINICAL RECOGNITION Hypertonus in Xon-thickened Arteries— Hypertonus in Sclerosed Vessels — Hypertonus and Relaxation in Atheromatous Arteries — Cases . . . . . .27 CONTENTS CHAPTER V THE CAUSES OF HYPERTONIC CONTRACTION PAGE The Influence of the Nervous System — The Influence of the Com- position of the Blood — Exjaerimental Work — Views of Clinicians — The "Localisation of the Action" on the Vessel Wall — Action of Adrenalin — Myoneural Junction — Action of Ergot — Action of Infundibular Portion of the Pituitary Body — Influence of Tobacco . . . . , . .33 CHAPTER VI THE CLINICAL ESTIMATION OF BLOOD-PRESSURE Arterial Tension and Blood -Pressaire — Methods of estimating Blood- Pressure — Influence of the Condition of the Arterial Wall — Factors determining Haemomanometer Readings — Tissues surrounding Arteries — Thickness of Arterial Wall — The Blood- Pressure inside the Vessel . . . . .43 CHAPTER VII A NEW SCHEMA OF THE CIRCULATION Description of Schema — Eff'ect of Constriction on the Pressure in the Tubes — Influence of the Thickness of the Walls of the Tubes — Result of High Pressure in thin-walled Tubes . . 56 CHAPTER VIII PRESCLEROSIS — HYPERTONUS VERSCTS BLOOD-PRESSURE — THE MODE OP PRODUCTION OF ARTERIO-SCLEROSIS Presclerosis — Views of Huchard, etc. — Mode of Production of Arterio-sclerosis — "Muscular E.xcitants" — Result of Continu- ance of Hypertonic Contraction . . . . .62 CHAPTER IX THE PRACTICAL APPLICATION OF THE PRECEDING CONCLUSIONS Resume of preceding Chapters — Vessel Sensitiveness and the Clinical Significance of Hypertonus — The Interpretation of Hfemomano- meter Readings — Angiohsemomanometer or Angiomanometer . 6"/ CONTENTS vii CHAPTER X HYPERTONUS AS SHOWX BY THE SPHYGMOGRAPH TAGE Illustrative Cases showins also the effect of Vaso-dilators . . 75 CHAPTER XI THE cli:n'ical significance and value of h^momanometer OBSERVATIONS IN ADVANCED INTERSTITIAL NEPHRITIS The Influence of the Vessel Wall in Heemomanometer Readings in advanced Interstitial Nephritis — Illustrative Cases — Interpre- tation of the Readings . . . . . .79 CHAPTER XII THE INFLUENCE OF THE ALIilEXTARY SYSTEM IN CAUSING ARTERIAL HYPERTONUS AND SCLEROSIS : FOOD, DIGESTION, CONSTIPATION, AND ALCOHOL Current Views as to the Influence of Food and Digestion — Physio- logical Phenomena during Digestion — Eff"ect of Excess in Diet — Effect of Intestinal Putrefaction — Putrefaction of Proteids — Effect of the Alimentary System on Sclerosed Vessels — Influence of the Alimentary System on the Adrenals — Illustrative Cases . CHAPTER XIII HoEMOilANOMETER PRESSURES IN CASES OF ACUTE ALCOHOLISM Cases of Acute Alcoholism with Low Pressure and with High Pressures — Effect of a Vasodilator added to the ordinary Treatment in the High Pressure Cases . . .113 CHAPTER XIV GROUPS OF CASES ILLUSTRATING H.^iMOMANOMETER READINGS Cases of Bright's Disease— Miscellaneous Cases— Cases of elderly and aged Persons— The Relation between the Radial and Brachial Arteries — Cases with Heart Symptoms — Importance of recognising Hyper tonus in Cardiac Cases . . .119 CONTENTS CHAPTER XV THE RELATION OF AXGINA PECTORIS AKD ALLIED CONDITIONS TO AN ARTERIO-CARDIAC REFLEX HAVING ITS ORIGIN IN THE ABDOMEN, AND CAUSING HYPERTONIC CONTRACTION PAGI Introductory — Historical — Views regarding Angina Pectoris — Angina Pectoris Vasomotoria — Intermittent Claudication — Lauder Brunton and Amyl Nitrite — What is included under " Angina Pectoris " "? — ConstructiA^e and Critical — An Arterial Abdominal Reflex — Exaggeration of Xormal Reflex — Action of Reflex on Sclerosed Arteries — Relation of Reflex to Angina Pectoris — Illustrative Cases — Clinical Pathology — Th e Unifying Principle ...... 121 CHAPTER XVI THE PHENOMENA CAUSED BY HYPERTONIC CONTRACTION OR SPASM CONSTRICTION OF CEREBRAL ARTERIES Contractility of Cerebral Arteries — Vessels acted on by Substances in the Blood — Application of this to Cerebral Vessels — Nerve In- fluence — Influence of Blood Composition — Eft'ect of Strychnine — Relation of the Pituitary Body to the Cerebral Circu- lation — Clinical Application — Transitory Phenomena — Accompaniments of Migraine — Illustrative Cases — Cases with recurring Mental or Motor Phenomena — Cases of permanent Paralysis or Paresis preceded by "Warning Attacks" — -Fatal Cases of Hemiplegia — Cerebral Softening from Vessel Constriction versics Htemorrhage — Case of Temporar}- Paresis accoftipanying Paroxysms of Angina Pectoris — Case of old-standing Hemi- paresis with Temporary Complete Right Hemiplegia and Aphasia — Case of Cheyne - Stokes Breathing with thick Arteries — - Clinical Pathology of the preceding Groups of Cases — Minor Phenomena and Focal Spasm — The Special Irritant — The Phenomena in Persons with Sclerosed Vessels — Temporary and Permanent Paralysis in Persons with Sclerosed Vessels — Softening or Htemorrhage ? — Symptoms due to a Feeble Circu- lation — Treatment . . . . . . 153 CHAPTER XVII CONCLUSION Order of Links in Chain of Evidence ..... 191 LIST OF ILLUSTRATIONS 1, 2. Sections of Arteries showing Elastic Tissue in Walls 2 3. Section of Atheromatous Artery . . . 18 4. Do. do. with recent Blood Clot 18 5, 6, 7. Sections of Atheromatous and Calcareous Eadial Arteries . . . . . 20, 22 8. Section of Artery showing Obliterative Endarteritis 22 9, 10. Sections of Radial Artery and of Kidney showing Arterio-sclerosis both from same Case . . 24 11, 12, 13. Sections of Radial and Coronary Artery and of Kidney all from same Case ... 24 14, 15. Sections of Normal Radial Arteries showing Hypertouus ..... 52 16. Section of Radial Artery showing Sclerosis . . 52 17. Section of Sclerosed and Hypertonic Radial Artery 52 18. Do. do. do. do. (pure Hypermyotrophy) ... 52 19. New Schema of the Circulation ... 57 20. Transverse Sections of Tubes used in Schema . 57 21-28. Sphygmograpliic Tracings illustrating Hypertonus . 76, 77 29, 30. Sections of Radial Arteries showing Hyper- myotrophy ..... 80 31. Sphygmograpliic Tracing .... 124 32, 33. Sections of Brain showing Areas of Softening . 175 34, 35, 36. Pulse Tracings from a Patient with Cheyne-Stokes Breathing . . . . . 179, 180 Dr. George Olivei-'s Hseniomanometer with Wrist Bag ...... 48 CHA.PTER I THE NORMAL STRUCTURE AND MOVEMENTS OF ARTERIES STEUCTURE : PULSATILE MOVEMENT ; TONE AND HYPERTONUS. Although it is fully recognised that the nutrition of the body as a whole, and the vigour of its component parts and organs, depend upon the blood supply, clinical attention is almost wholly directed to the condition of the blood itself — to the enumeration of its corpuscles and the estimation of its htemoglobin richness. The condition of the channels by which the blood reaches the various organs receives but scant con- sideration, although it is only necessary to mention the neglect to make it apparent that such neglect carmot be wise. Our purpose in these pages is to direct attention to the important part taken by the blood vessels in the production of clinical phenomena, varying in intensity from trifling indisposition to severe illness in which life is seriously and often immediately threatened. The subject is very wide, and no attempt will he made to cover the whole field. Only those conditions will be dealt with which are fundamental and specially illustrative. As a preliminary to our investigation, it is necessary to recall the anatomical structure and nervous relations of the blood vessels. Arteries consist of three coats : the external coat, or tunica adventitia, is formed of connective tissue in which there are nerves, lymphatics, vaso-vasorum, and in addition a considerable layer of elastic fibres next the media, not commonly described ; the middle coat, or tunica media, is A PULSATILE MOVEMENT, TONE, AND HYPERTONUS formed of unstriped muscle fibres, which run transversely and thus surround the vessel ; the internal coat, or tunica intima, is formed of a layer of polygonal endothelial cells with a fine line of sub-endothelial connective tissue underlying them. In some of the arteries there is an elastic lamina between the internal and middle coats, and another between the middle and external coats. These are known respectively as the internal and external elastic laminm ; they are by no means con- stantly present, and often only the internal one is represented. In the large arteries the middle coat is made up to a great extent of elastic fibres. The arteries are supplied with nerves, which connect them with the vasomotor centre in the medulla. The muscular tunic of arteries has, like muscle everywhere else, what is known as tone or tonus. This is a sustained measure of contraction of its individual fibres, which may be increased or diminished. It is commonly taught that it is regulated by nervous influences conveyed through the sym- pathetic, the constrictor fibres of which when stimulated lead to an increase of tone, or even to a distinct degree of abnormal arterial contraction ; while the withdrawal of sympathetic action leads to lowering of normal tone, or to a definite relaxation of the arterial wall. While the tone of arteries can be thus controlled by the sympathetic, there is the authority of Leonard Hill for the observation that it is soon restored after section of the vaso- motor nerves. The tone under such circumstances is regarded by him as being then maintained by the blood-pressure. It will be subsequently shown that another factor has to be taken into consideration when tone is lowered or increased, as it is in the disorders which come under the notice of the physician. In considering the movements of arteries, it is to be noted that they have firstly a pulsatile movement — probably a rhythmical response to the rhythmical flow of the blood, corresponding with ventricular systole and diastole. It is probably not merely the stretching and contraction of an elastic tube by a wave passing along its contained fluid, but the same kind of unceasing rhythmic movement the heart possesses. However that may be, it is important to divest 2 M Fig. 1. — Int., in the lumen of the artery, showing near it the multiplication of the internal elastic lamina ; M, tunica media ; EF, the layer of elastic fibres external to the tunica media. Fig. 2.— The description to Fig. 1 is a^Dplicable to this fio-urc also. {The sections from which these micro-photograxilis were taken icere kindly prepared for me It/ Miss Huie.) PULSATILE MOVEMENT, TONE, AND HYPERTONUS our minds of the current notion that the arteries are a mere system of elastic tubes. In addition to the pulsatile movement, there is a further movement, which is allied to tone, and yet is such an abnormal exaggeration of it that the terms contraction, con- striction, and spami have all been applied to it. Although occasionally recognised, it has been to a great extent ignored ill clinical medicine, and its significance has, as an inevitable consequence, been overlooked. The thought of " blood- pressure " has possessed the field, to the practical exclusion of the arterial wall. The accentuation of this normal movement is of great clinical significance, and as it varies within wide limits it is desirable to have words or terms to express the differences. The normal degree of tonicity varies, and it varies under conditions which are to be regarded as normal. It is there- fore impossible to do more than have a somewhat empirical nomenclature to define its variations. What is of practical importance is to know that the tonicity does thus vary ; to be able to recognise dift'erences when they are present, and to understand that such variations are no mere chance phenomena without cause or significance. The normal tonicity or tone is to be noted in the soft vessel of perfect health. This tonicity is increased under physiological conditions, as during digestion and during physical effort. This is a physiological hypertonus : no other term expresses the fact : it is an increase of a normal state due to an increase in the intensity of normal stimuli. The term hypertonus has sometimes been objected to since I introduced it in this connection, but a word was required that would carry the idea which has been indicated. When the hypertonus occurs in an artery the increased measure of contraction of the muscular coat, which is necessarily implied, means that the wall of the vessel becomes somewhat thicker, that its dia- meter is somewhat reduced, and its lumen correspondingly diminished. The degree of contraction may exceed the limits of normal variation, and when it does so the term hypertonic contraction, or merely arterial contraction, will be used here. The word contraction has such a variety of meaning in medicine, and so commonly means a narrowed orifice or a 3 PULSATILE xMOVEMENT, TONE, AND HYPERTONUS strictly limited constriction in a tube, that it reqnires the adjective hypertonic to indicate an effect which is wider and more generalised through the arterial system. The term hypertonic contraction will therefore be used to indicate this greater degree of arterial constriction. There is yet another condition, differing from the preceding in being a localised constriction. In the two preceding conditions, the "hypertonns" and the "hypertonic contraction," the contrac- tion affects the whole systemic system. In the third con- dition the arterial constriction is localised, and may be so extreme in degree as to greatly diminish or completely shut off the blood flow in the affected vessels ; to this condition the term arterial sjmsm is most suitably applied, and will be confined in these pages. It will from this be realised that the morbid is but an exaggeration or an intensification of the normal process. The reverse of hypertonns is loss or diminution of tone. REFERENCE. Leonard Hill, Schiifer's Physiology, 1900, vol. ii. p. 138. CHAPTER II BLOOD-PRESSURE AND ITS RELATION TO VESSEL CONTRACTION AND HEART POWER During the past few years greatly increased interest has been taken in the important subject of blood-pressure, and in the means of clinically measuring it. It is therefore necessary to consider certain questions which have risen up around these, especially those which are of clinical importance. In no department of practical medicine is correct knowledge so essential for the satisfactory translation of mental conception into practical understanding and therapeutic application, and in this chapter I shall endeavour to make this evident. Blood-pressure is determined by several factors : first, by the driving power of the left ventricle ; second, by the channels in which the blood flows ; and tliircl, by the condition of the flowing blood. The second of these may be sub- divided ; but for the present it is important to realise that these embrace all the factors, and are the only factors which determine the measure of the blood-pressure. The blood-pressure is, of course, the pressure exercised by the flowing blood inside the vessels. Physiologists measure it by means of a cannula introduced into a vessel, and com- municating with a manometer outside it. In this way an accurate record is obtained of the pressure in the left chambers of the heart, in the great arteries, and in the great veins where they empty their blood into the right auricle. Observations of this nature are made on healthy animals. Certain of the observations made on such a system of tubes as is provided by the vessels fall within what we may call the ordinary laws of physics ; others of them are the result of the whole circuit, consisting of living structures, 5 BLOOD-PRESSURE AND VESSEL CONTRACTION being influenced and played upon both by a nervous system, and by the flowing blood itself, which is in constant contact with it. Some of the 'pliydcal facts are as follows. Starting from the left ventricle, the blood-pressure is highest in the aorta, and falls gradually towards the capillaries, which may be regarded as the periphery. This is true of the flow of any kind of fluid through a system of tubes. The fall in pressure, as the periphery is approached, is the result of friction between the flowing fluid and the wall of the tubes. A thick fluid flows less readily than a thin fluid ; in small tubes the obstruction is greater than in large ones. In the circulation, as it is seen in living animals, vital ])rocesses have to be considered, for they often determine physical changes. It is of great importance to separate these two sets of phenomena when circulatory disturbances are considered. To illustrate this, we may suppose that, as the result of vital influences, the vessels in a considerable area become contracted, and the circulation through them thereby impeded ; the blood-pressure in the vessels above the area of constriction is raised as a necessary consequence. This takes place in an artificial scheme formed of rubber tubes as certainly as in the living vessels. Such a raising of pressure, if it is sufficiently great, will travel back to the aorta ; if it is confined to a limited area the increased pressure will be lost before the aorta is reached, in virtue of the elasticity of the tubes. The mean or average pressure over the whole system is not affected so long as the driving power of the heart remains undisturbed; the distribution of the 2^resstire is, however, altered, — where the vessels are constricted the pressure falls, where they are not constricted it is raised. The fall and the rise balance each other, and so the mean pressure is not altered. As has been said, the pressure in the aorta is often raised under the circumstances indicated, and it is this fact which has given rise to the dictum that peripheral constriction or ohstruction raises hlood-jjressure. The dictum would certainly be found to occupy an honoured place in a "Proverbial Philosophy" of medicine, did such a compilation exist; but like all such dicta, it is false as well as true, and it would demand considerable ingenuity to 6 BLOOD-PRESSURE AND VESSEL CONTRACTION determine which aspect predominates. In a limited sense it is miimpeachable, yet it has had the most unfortunate results in practical medicine. It has been the common answer to many questions, and has stopped the mouths of many inquirers and seekers after truth. Peripheral constriction, no matter how caused, raises blood pressure — but where ? Is it in the constricted vessels them- selves ? Prom much that has been written the question might be answered in the positive, and yet the conception is de- plorably misleading as a practical guide. The rise of pressure is behind the constriction, and the physiologists measure it in the aorta. The physical law is perfectly simple when truly applied : if the capillaries constrict, the rise in pressure is in arterioles ; if the constriction includes arterioles, the raised pressure tells from the small arteries backwards, and so farther and farther back. The whole mixed conception that a con- stricted vessel has its blood-pressure raised has to be abandoned for a more accurate and infinitely more illuminating concep- tion of the changes w^hich take place. When the raised blood-pressure reaches so far back as the aorta, what is its effect ? In direct proportion to the increase of pressure in the aorta is the increase of power required by the left ventricle to open the aortic cusps and to expel its blood. This is how the raising of pressure leads to increased heart effort. If the myocardium be sound it does this in virtue of its reserve of power, which is called out through the medium of the nervous mechanism. The raising of aortic blood-pressure is the inevitable 'pliij&kal consequence of a peripheral constriction, which is a xital phenomenon, while the response of the heart is again a mtal phenomenon. It is thus seen how" essential it is to separate mechanical and vital factors. The response on the part of the heart is commonly represented as intended to maintain blood pressure ; it seems ofteii to be thought of as maintaining the pressure all round. If the heart did not respond there would be a fall in aortic pressure ; but if it responds in proportion to the rise of pressure in the aorta, the mean is maintained, but the maintenance of the mean does not imply that an increased flow occurs in the area w^here the vessels are constricted. The conception that the heart is constantly battling to meet 7 BLOOD-PRESSURE AND VESSEL CONTRACTION the cry of the tissue cells for a sufficient blood supply, as a mother tends her young, is a very pretty conception, but is disproved by many morbid processes. What the heart has to cope with is the enemy at its gate — the mechanical difficulty of raised aortic pressure ; and I question if the heart does more than overcome that. The circulation as a living scheme has, however, more than one way by which the heart can be saved from the strain of such a change as has been indicated. If the systemic system be constricted the splanchnic area may dilate, and thus ease aortic pressure. The heart itself has its regulating mechanism, so that, if the aortic pressure be more than it can completely overcome, an increase of residual blood in the ventricle leads to over-distension, which so affects the vagus terminals that the heart is slowed, and the blood is given more time to pass through the constricted vessels. If the splanchnic area be dilated, as during digestion, the systemic vessels commonly become somewhat constricted, doubtless to adapt themselves to the determination of so large a volume of blood to the abdomen. This maintains aortic pressure, which might be dangerously lowered by the sudden influx of blood to the splanchnic area : to regard the condition in the systemic vessels as a raising of blood-pressure to provide the tissues supplied by the systemic vessels with sufficient pabulum, is one of the most curious of the concep- tions whicli adorn this subject. There is another aspect of the circulation which must be kept in view when considering the effect which peri- pheral changes have upon the heart, namely, this, that when the flow at the periphery is diminished, from constriction of the vessels, blood tends to accumulate on the venous side ; less blood then reaches the heart, and the output of the heart, as is well known, is dependent in part on the amount which flows into it. It is equally well known that the venous system can hold all the blood in the body, that, indeed, the splanchnic vessels themselves can do so to such an extent that it is said a man can be fatally bled into his splanchnic vessels. It has therefore to be kept clearly in mind that the vital side of the circulation provides abundant means for easing off 8 BLOOD-PRESSURE AND VESSEL CONTRACTION aortic pressure when it threatens to become excessive, and that even on a priori grounds the enormous increases in so- called blood-pressure which are recorded, at once ought to arouse the suspicion that there has been something wrong in the method of examination, or in the interpretation of tlie records obtained. When systemic hypertonic contraction occurs, the radial arteries participate in the contraction, and this contraction is commonly regarded as " raised blood - pressure," — an error which owes its origin, iirstly, to the ignoring of the fact that the arteries are contracted ; and secondly, to the conception that the rise in blood-pressure which occurs in the aorta means a rise of pressure in the radials also. In some circumstances, which will be dealt wdth later, it can most reasonably be assumed that the general con- striction of vessels which occurs is for the purpose of saving the tissues from an impure blood ; while on the other hand, did we regard the successfully struggling heart as stimulated by the nutritional needs of the tissues, we should have to accept the existence of two antagonistic processes, main- taining an internecine strife for supremacy — the arteries exercising the right to protect the tissues, the heart heed- lessly insisting on forcing through the impure and hurtful blood. And yet it seems to me as if much that has been written on the subject, say, of granular kidney, had this underlying conception for its inspiration. The position comes to be this — that peripheral con- striction raises aortic blood-pressure, and unless this can get relief by dilatation and an increased flow in another peripheral area, the heart requires increased power to overcome the increased aortic pressure. The conception of increased pressure in the constricted area, to be correct, would imply a heart effort of great magnitude, while all that the heart is really called upon to do is to empty its left ventricle contents into the aorta, the pressure in which while heightened can be eased off and relieved in the ways already referred to. For the heart to successfully cope with increase of aortic pressure, it has the reserve of power which has been already referred to. This is well and fully recognised. The exercise of this reserve leads in favourable conditions to heart hyper- 9 BLOOD-PRESSURE AND VESSEL CONTRACTION trophy ; but it has l3een wisely insisted upon by Broaclbent and others that the very existence of hypertrophy implies that part of the reserve has already been drawn upon, and therefore that the hypertrophied heart has less reserve than the non-hypertrophied one. In practical medicine we can go further than this, for it is equally well known that the reserve of power is often very small, and may be almost absent. In some instances the response to a call for even a little extra work may be followed by an exhaustion so extreme as to be fatal. The left heart, in such myocardial degenerations as cloudy swelling, fragmentation, fatty degeneration, acute and chronic interstitial carditis, not only possesses a low driving power, but any reserve it has is of the most flimsy character. This is shown by the embarrassment caused by the slightest movement, in extreme cases ; by the disturbances of the circulation which accompany gastric digestion, or any burden thrown upon, or any disturbance of, the alimentary tract. In the right heart not only do the changes just mentioned occur, but it is in addition the special site of fatty infiltration. This lowers the normal reserve of the right ventricle, so that any pulmonary difficulty or physical effort may suddenly over- w^helm it. In the normal sound animal, including man, increased strain calls out the reserve, and increased work is done. Every clinician, however, knows that the strain, to be suc- cessfully endured, depends upon the condition of the individual heart. It is common enough to see persons who have over- taxed their hearts, in w^hom the strain has exceeded the reserve, with the result that dilatation occurs, and the heart is promptly placed on a lower energy level than it previously occupied. In the first half or so of life, the period of greatest physical activity, this over-strain is rarely immediately fatal ; but in the second half of life the risk is greater, and as life advances the danger becomes more urgent. This effect of age upon the circulation is universally recognised ; but while this is so it is important to emphasise the fact that the myocardium differs greatly in individuals of the same age from youth onwards. This means, of course, that in different persons, at the same period of life, the heart reserve varies within wide limits, so that the general proposition that the lO BLOOD-PRESSURE AND VESSEL CONTRACTION heart rises to the strain put upon it has in the iudividual at every period of life its Hmitations and qualifications. Seeing that the measure of the normal or sound state varies with the individual, it follows that, while the physiological principle holds, the function of the physician is to estimate the power, and the probable reserve of power, in the individual ; and to recognise the effects of over-strain, however brought about. In this estimation it is necessary, indeed essential, to keep the two factors embraced in the problem always before us : the first is the work to be done, which constitutes the obstruction from the standpoint of the circulation ; and, second, the power to do the work, which is synonymous with the driving power, and the reserve of power, of the ventricle, on which the strain is mainly thrown. The problem, while always presenting the same equation, requires that the value of its terms be determined in every individual instance. It is herein that both the difficulty and the interest of the physician's work lies ; and herein is one illustration of how the physician, while using the physiologist's work, may branch off from him. It has been seen how the general proposition is true, that when extra strain is thrown upon the heart it responds by extra work ; and yet how that proposition has to be modified and limited by clinical observation. The extra strain upon the heart, it may be presumed, comes as a rule through changes in the vessels. Any increase of resistance in the vessels, no matter how produced, leads to extra strain on the heart. Two factors may he regarded as possibly causing increased resistance : the first is change in the condition of the circu- lating blood. An increase in its viscosity or specific gravity would certainly impede its passage through the capillaries : but we have on this point little or no knowledge which is of practical value, and seeing that fluid so readily passes into and out of the blood, it is very doubtful whether it will be found to be a factor of any appreciable practical importance. The second factor leading to increased resistance is an alteration in the blood channels themselves. Any narrowing of their calibre is undoubtedly a cause of resistance. That they do so narrow is also l^eyond question, although the importance of the fact has hitherto been obscured by the one- sided attention and devotion to the vessels as a mere system 1 1 BLOOD-PRESSURE AND VESSEL CONTRACTION of elastic tubes. Seeing the resistance lies in the vessels themselves, the clinical problems with which we propose to deal will be considerably simplified. In the normal state this narrowing of the vessels calls out the necessary extra work from the heart needed to overcome the increased pressure which, as we have, seen, occurs in the aorta ; this is the normal response of extra work to extra strain on the part of the heart. Upon our conception of what constitutes the extra work so brought out, much, it will be seen, depends. The circumstances we are at present considering are the resistance offered by a constricted set of vessels on the one hand, and a left ventricle with the ordinary amount of blood to empty itself of on the other. With these premises it follows that if the heart has sufficient reserve to do this the increased pressure in the aorta will be maintained. If, on the other hand, the heart has not the necessary reserve the ventricle is not emptied by systole ; and if in any degree it fails to empty itself, the blood - pressure in the aorta is correspondingly lowered. I do not think there is any other true picture of what takes place under the circumstances with which we are dealing, and which are of common and ordinary occurrence. We may go a step further, with apparently equal safety, and say that in certain states of the myocardium it is incon- ceivable that the heart can do the extra work necessary to raise the blood-pressure. With tlie enfeebled heart of debility, with the degenerated heart of antemia, how is it possible to have a raised blood-pressure in the only sense in which raised blood-pressure is of practical value to the clinician ? It is necessary to lay stress upon the contention that to the clinician the all-important factor in questions of blood- pressure centres in the heart. When the vessels constrict in one region, the heart may be so powerful that the danger is vessel rupture in another ; on the other hand, the heart may be so feeble that there is imminent risk of syncope. With incomplete conceptions of " peripheral resistance " and " blood- pressure " the central factor may be obscured. Whatever tends to lead away from this view of the circulation, and whatever methods tend to obscure this aspect of it require to be employed with great caution. This matter will, however, be dealt with more fully later. 12 CHAPTER III DISEASES OF ARTERIES INTRODUCTOEY : ATHEROMA ENDARTERITIS DEFORMANS : OBLITERATIVE ENDARTERITIS ^AORTITIS : CALCAREOUS INFILTRATION OF TUNICA MEDIA : ARTERIO- SCLEROSIS. INTRODUCTOEY. The difficulty which presents itself when diseases of the arterial wall have to be considered is to be attributed to the names used to designate the conditions met with, and the confusion which exists between clinical observations, pathological teaching, and the terms used. In illustration of this it is only necessary to recall the fact that in Britain and elsewhere the term atheroma was used to denote per- fectly definite pathological changes in vessels, while clinically it was commonly applied to all thickenings of arteries examined for clinical purposes. The artery mainly examined was, of course, the radial artery, and the condition of it came to be regarded as, in great measure, an index of the state of other arteries throughout the body. It was, how- ever, known that the condition of the radial artery was not a certain index of the condition of the cerebral or of the coronary arteries — there was no invariable relationship — yet the relationship was sufficiently constant to warrant considerable clinical importance being laid upon changes in it. It is quite within the limits of accuracy to say that all changes in the radial artery were spoken of, and thought of, as atheroma ; and that atheroma was mentally pictured as a thickening with degeneration pi the arterial 13 DISEASES OF ARTERIES wall. In fact, the conception was that of a degenerative thickening. It was further universally held that atheroma necessarily implied a rigidity of the artericd wall, and a loss in its elasticity. As a result of this line of thinking, based ujDon incomplete pathological observations, thickened arteries were regarded as atheromatous arteries, and, as atheromatous arteries were rigid arteries, therefore all thickened arteries were rigid, — such was the common reasoning. Comparatively recently there was introduced from Germany the term arteriosclerosis, which has been applied by the Germans as widely as the term atheroma has been applied in this country. They, however, distinguished between a local or nodular and a diffuse arterio-sclerosis. As etymologic- ally the term means a hardening or induration of the arterial wall, it is applicable to nearly all forms and varieties of arterial disease. From this standpoint there is no fault to find with it, but its introduction did not help the clinical position, for the new term simply replaced the older one, without carrying any more precise pathological conception with it. It was rapidly attaining much the same position as " that blessed word Mesopotamia " had in • the Highland woman's scheme of theology. In 1901, when my first paper deahng with this subject was published, I gave a short historical summary of the position, which I may include here. Twenty years ago the term arterio-sclerosis was so unknown to British medical terminology that it was not even mentioned in the two admirable text-books published about that time respectively by Bristowe and by Fagge. Going fourteen years further back, Dr. Noel Gueneau de Mussy wrote a historical resume entitled Etude Clinique sur les Indurations des Artercs ; this term induration included atheroma. The term arterio- sclerosis is, as has been said, of German origin, and the German pathologists and clinicians certainly apply it to atheroma. Ziegler, after saying that sclerosis in an artery implies the existence of local thickening of its inner coat, proceeds to describe typical atheroma. At the same time, he did not confine the term to atheroma, for he also noted that the renal arteries and their branches in aged people are very frequently the seat of sclerotic changes, which may 14 INTRODUCTORY simultaneously affect the arteries of other regions also, or be confined to the kidney. In this condition the intima of the arteries was notably thickened, and the lumen corre- spondingly narrowed or even obliterated ; and he showed that this vascular change in the kidney gave rise to a special form of contraction of the organ, which he termed arteriosclerotic atrophy. Of all the German work, however, there can be no question that it was Thoma's which specially influenced opinion in this country and in America. To borrow a term from social life, he may be said to have " set the fashion " in the use and interpretation of the term in clinical medicine, and, so far as we have been able to find, pathology has not let its voice be heard beyond the lecture-room. Thoma's views may be briefly summarised as follows : the elasticity of the vessel wall becomes reduced in general diseases, acute and chronic infective diseases, long-continued disturbances of general nutrition, by many poisonous substances, and by functional overstraining of arteries from an increase of the heart's action. As a result the lumen dilates and the blood stream is retarded in the widened vessel. This retardation is the cause of a new formation of connective tissue in the intima of the widened artery. " The new formation of connective tissue in the intima renders the vessel wall more firm, so that it appears more rigid and less yielding (arterio- sclerosis, phle])o-sclerosis, angio-sclerosis)." In short, Thoma holds that the thickening of the intima is secondary to a dilatation of the vessel, and consequent on slowing of the l^lood stream ; that the thicken- ing is to compensate for the assumed widening, and to restore the equilibrium between lumen and contained blood which had been lost. By this means, he maintains, the rapidity of the blood flow is re-established. If we turn to the French school we find Lancereaux in 189 3 writing on " L'Endarterite ou Arterio-sclerose Generalisee." He defines the conditions as a proliferation of the cells of the intima, which goes on to fatty degeneration due to failure of nutrition. Huchard mentions the fact that German authors always use the term arterio-sclerosis to signify atheroma of arteries, and he asks whether the terms are absolutely synonymous. His answer is in the negative. He 15 DISEASES OF ARTERIES uses the term to designate a general condition of which atheroma is only one of numerous manifestations. These include visceral scleroses — all dominated by a primary chronic inflammation of the small vessels described by many authors as obliterative endarteritis (or endarteriolitis). Arteritis of the small vessels, in short, he considers the anatomical characteristic of arterio-sclerosis (p. 96). Turning to English works of recent date, it is not necessary to go beyond the valuable System of Medicine which has been edited by Professor T. Clifford Allbutt. Here we look for a true representation of contemporary medicine, and in Dr F. W. Mott we find an exponent of the German view of arterio-sclerosis and an adherent to Thoma's views which have already been referred to. He places the term " arterio- sclerosis " as the title of the section, and in the introduction to the sul^ject he says that the term " is applied rather loosely to a thickening of the vessel wall. It includes the obvious naked-eye change in the large arteries, named by some authors atheroma ; by others, endarteritis deformans. It includes also arterio-capillary fibrosis, a change first described by Gull and Sutton in the walls of the small vessels, which only becomes obvious on microscopic examination." At page 320 he gives as his definition of arterio-sclerosis, " a local or general thickening of the arterial wall with loss of elasticity, occasioned mainly by fibrous overgrowth of the tunica intima, secondary and proportional to weakening of the muscular and elastic elements of the media." It seems quite clear that Dr Mott includes atheroma under the term arterio-sclerosis, and he follows Thoma in asserting that the primary change in atheroma is to be found in a degeneration of the tunica media, and that the thickening of the tunica intima is secondary and compensatory to this. He holds with Thoma that the observations made by the latter on paraffin moulds of the aorta prove this, without apparently seeing that these moulds may with equal justice be held to prove that the atrophy of the media is secondary and complementary to the hypertrophy of the intima. It is not my purpose at present to elaborate this point, but I would indeed be surprised to find that British pathologists held this to be the order of events in atheroma. i6 INTRODUCTORY Passing from this question of the inclusion of atheroma in arterio-sclerosis, we find that Dr Mott describes a " diffuse arterio-sclerosis " (p. 329) in which the changes begin in the small arteries and capillaries, es^Decially those of the renal cortex, brain, and heart, and are frequently associated with " nodular atheroma " of the aorta. He says that " on minute examination the muscle fibres of the media show hyahne swelling, fatty degeneration, or atropine changes, so that the muscular elements are often not recognisable ; this is especially the case in the small arteries of the kidney, where the wall of the vessel may appear to consist of a homogeneous hyaline tissue. Sometimes the degenerated atropliied fibres of the media can be made out, but nothing of the elastic lamina, the intima being thickened and represented only by a homogeneous hyahne material with but few nuclei. The result of these widespread changes is increased resistance to flow of blood through the capillaries, hypertrophy of the left ventricle, dilatation of larger arteries from degenerative changes in muscular and elastic tissues of the media, slowing of the circulation, and compensatory proliferation of the subendo- thelial layer of the inner coat" (p. 330). Here, again, Dr Mott strongly commits himself to Thoma's view. In America, Osier, Councilman, and others, have committed themselves to Thoma's views. From this risume, which may be taken as fairly repre- sentative of authoritative views, it is seen that the term arterio-sclerosis is apphed to three conditions — (1) To atheroma; (2) to a generalised endarteritis; and (3) to a thickening of the intima, compensatory to dilatation of vessels from weakening of their middle coat. This resume could not, however, be regarded as even approximately complete without reference to various views on the relations between granular kidney and the changes in the arteries and heart which accompany granular kidney. In fact, no exposition of arterial changes could suitably ignore this side of the question. George Johnson (1850—1873) was the first to show that thickening of the muscle coat of the arteries occurred in granular kidney, and he held that the changes in the heart and vessels were secondary to primary kidney changes. Gull B 17 DISEASES OF ARTERIES and Sutton (1872—1877) propoimded the view that there occurred a generalised change or disease in the vessels, to which they gave the name, " arterio-capillary fibrosis." The changes in the kidney were regarded as secondary to this vessel fibrosis. Dickinson (1875) held that a growth of fibrous tissue in the kidney was the primary change and that the changes in the vessels were secondary to this. Eosenstein (1881) agreed with Johnson as to the thickening of the muscular coat of the arteries, but thought that the thickening of the iutima was inflammatory. Ewald (1881) held that there were two forms of changes in the vessels connected with Bright's disease — first, that in which the kidney was affected primarily and was followed by hypertrophy of the heart and of the muscle coat of the arteries; and, second, that in which disease of the general vascular system was the starting-point of the kidney disease. In this latter there was arterio- capillary fibrosis, both in the kidney vessels and in the general vascular system. He thought that it was a question whether such cases should be called " Bright's disease " or not. Dreschfeld and Mahomed (1881) held practically the same view as Ewald, the latter holding in addition that there might be cardio-vascular changes without necessarily renal changes being present in all. Dr. Samuel AVest carried the discussion down to 1906, and discourses on the old theme as to whether the kidney lesion or the arterial change is the first to appear. He enters a protest against granular kidney being considered partly under vessels and partly under kidney. Having thus outlined the state of opinion and belief, we may now tm'n to the consideration of the pathological changes occurring in arteries which are of practical import- ance to the clinician ; and I shall deal with these in the following order : — 1. Atheroma — endarteritis deformans. 2. Obliterative endarteritis — acute aortitis. 3. Calcareous infiltration of the tunica media. 4. Arterio-sclerosis. I adopt this order, as the first three conditions have been long known and taught in this country, while the fourth is practically a new entity, and the one which is mainly treated of in this book. I adopt and annex the i8 Fig. 3. — Atheromatous artery ( x 15). I, the thickened and atheromatous tunica intima ; M', the atrophied media correspond- ing to the atheromatous part ; M, the hypertrophied tunica media, where there is no atheroma. Fig. 4.— Atheromatous artery ( X 16). I, thickened and athero- matous intima ; M, hypertrophied media ; M', atrophied media ; EL, internal elastic lamina ; B, recent blood clot. ATHEROMA AND ENDARTERITIS DEFORMANS term " arterio-sclerosis," as it is already in use, and as it is imdesiraljle to multiply terms. To my mind it is quite reasonable to give a new term a limited application while declining to acquiesce in its displacing older and more definite terms. ATHEROMA AND ENDARTERITIS DEFORMANS. Atheroma is a focal or patchy affection of arteries. It is characterised by a local thickening and degeneration of the tunica intima. The thickening consists of a hyperplasia of the subendothelial connecti\"e tissue. It is, however, early associated with an atheromatous degeneration in parts of this thickened intima. The atheromatous change is a fatty degeneration, commonly most marked in the deeper part of the thickened tunic. The atheromatous material may become the seat of more or less calcareous deposition. At the part corresponding to these changes the tunica media is thinned and atrophied, or may even show areas of necrosis in the large arteries, as demonstrated by Cowan and others. When these changes are still further advanced and are present in the large arteries, they lead to so much deformity that the term endarteritis deformans was applied to them by the older pathologists. In the large arteries, in addition to the changes mentioned, there may be found atheromatous cysts, atheromatous ulcers, calcareous plates (the result of calcareous deposition in extensive atheromatous areas), and local sacculations or bulgings, the result of yielding of parts of the arterial wall Ijefore the blood- pressure following upon the atrophy or even destruction of the tunica media. The changes may be so extreme, and may so affect the arch of the aorta for instance, that it may be much dilated, a state of matters to which the term aneurismal dilatation is appKed. Similar changes affecting a localised area of the aorta give rise to a definite aneurism. It is however as atheroma affects smaller vessels that we are specially concerned here ; so it requires somewhat more consideration. The condition is very common in the cerebral and in the coronary arteries, but is comparatively rare in the 19 DISEASES OF ARTERIES radials. Wherever it is present it may give rise to local bulging of the vessel wall, but such bulgings do not necessarily imply a yielding of the wall. The walls at the affected points are usually much thickened and the lumen is often greatly encroached upon, lessening in a very important degree the •blood channel. The thickening never uniformly affects the whole circumference of the vessel ; it is always asymmetrical ; it only affects small areas ; it never uniformly affects long stretches of an artery, although there may be many areas closely placed to one another. It thus differs entirely from the condition to be described as arterio-sclerosis. Etiology of Atheroma. — Atheroma is thus a focal affection of the arterial wall, affecting separate and limited areas. The changes indicate, not only points or areas of irritation, but an irritation associated with degeneration, and it is this association which characterises atheroma. The combination is what we expect to find produced by a micro- organismal cause. The theory that the degeneration is the result of impaired nutrition, due to obliteration of vasa vasorum, is quite untenable, for the following reasons, namely, that the degeneration often appears early when there is but slight thickening of the iutima ; the vasa vasorum may not be obliterated ; and in obliterative endarteritis no such degeneration occurs, although the intima may be much thicker and the vasa vasorum be markedly affected. Dr. John Cowan of Glasgow has made some interesting researches, from which he contends that atheroma may apparently be due to a number of conditions in which micro-organismal infection of the arterial wall is probable. Now that attention has been directed to this subject, I may say that I think it probable that atheroma may ultimately be found to belong to the enlarging series of affections having as their immediate cause a micro-organismal implantation. The typical and classical changes present in atheroma are seen in Figs. 3 and 4. In Figs. 5, 6, and 7, atheroma gone on to advanced calcareous infiltration is shown, the figures being taken from sections of radial arteries which to the finger were recognised as hard, rigid, and calcareous during life. In all these arteries a certain amount of fairly sound muscular tissue has persisted, 20 Fig. 5. — Atheromatous and calcareous radial artery ( x 15). C, atheromatous and calcareous ; C, media calcareous ; M, hypertrophied media ; A, tunica adventitia. Fig. 6. — Calcareous radial artery ( x 15). C, the calcareous tunica intima ; M, portions of thick tunica media. OBLITERATIVE ENDARTERITIS while in Fig. 5 it should be noted that nearly one-half of the circumference of the artery shows, not only an undegener- ate, but a hypertrophied muscular coat. This anatomical fact is of clinical importance, as will be shown in a later chapter. OBLITERATIVE ENDARTERITIS AND ACUTE AORTITIS. The description of obliterative endarteritis, as it occurs in smaller arteries, is usually taken from the syphilitic affection found in the brain. The affection there is usually nodular, in the sense that it affects a limited l^it of vessel, leading to such thickening that a considerable node or nodule is formed. The minute change is a thickening of the tunica intima, the thickening being the result of a hyperplasia of its cells. It differs, however, from the intimal thickening in atheroma in involving the intima somewhat uniformly, right round the vessel, and in showing no degeneration. The hyperplasia which leads to the thickening is progressive, and in its progress encroaches upon the lumen of the vessel, which is reduced to a minute size, or is entirely occluded. AVhen an artery is examined in the acute stage a considerable amount of small-celled infiltration is present in all three coats. These changes in cerebral vessels are regarded as always syphilitic. Corresponding anatomical changes occur in the arteries of the kidney in arterio-sclerotic atrophy, and in chronic interstitial nephritis ; they are also met with in the lungs in fibrosis, and m the neighbourliood of scirrhus cancer. In these latter a small-celled infiltration of the coats of the vessel does not occur, but the thickening of the intima goes on to complete obliteration of the vessel. A corresponding anatomical change also occurs in the smaller nutrient arteries in the brain. In none of these — especially in the lungs, kidneys, and of course in cancer — is the change regarded as of syphilitic origin. I shall again refer to these changes, as they are seen in the kidneys, under Arterio- sclerosis. In the aorta an acute aortitis occurs, giving rise to grey, raised, almost gelatinous - like areas, which on minute examination show hyperplastic thickening of the tunica intima 21 DISEASES OF ARTERIES and areas of small-celled infiltration in all three coats. This condition, which anatomically entirely corresponds with the obliterative endarteritis of the smaller syphilitic arteries, I hare always regarded as of syphilitic origin. The condition, as it occm\s in the cerebral arteries, is represented in Fig. 8. CALCAREOUS IXFILTRATIOX OF THE TUNICA MEDIA. Clinically, calcareous infiltration of the tunica media is indistinguishable from calcareous infiltration of the thickened intima in atheroma. In fact, in advanced calcareous infiltra- tion, it is by no means always easy to determine how much of it is intimal and how much medial. This is owing to the fact that when it is intimal there is so little of the media left that the doubt arises whether it is not the media itself which is infiltrated. The position of the elastic lamina often effectively helps in this determination. The change is one which does not require fuller consideration here. In Figs. 5, 6, and 7, the media is more or less involved in the calcareous infiltration. ARTERIO-SCLEROSIS. In 1901, in a paper read before the Edinburgh Medico- Chirurgical Society, I submitted the results of the examination of the radial and other arteries, taken from sixteen cases which had been under my care, and in which there had been marked thickening of the radial arteries during life. Since that time I have examined many additional cases, but they have only confirmed my previous observations, that the changes were totally different from those in atheroma, and strengthened the opinion I then expressed, that as the term arterio-sclerosis was in common use it ought to be retained, but its application confined to the changes which I then showed to be present. The changes may be defined roughly, as great thickening of the wall of the artery, with diminution in the size of its lumen. The changes which led to the thickening, when examined in detail, were seen to consist of — (1) a marked thickening of Fig. 7. — Very calcareous radial artery ( x 15). Only a small portion of tlie riglit and ujiper part of the wall not involved. ,\^ Fig. 8. — Obliterative endarteritis of syphilitic origin ( x 16). A, tunica adventitia ; M, tunica media ; I, greatly thickened tunica intima. ARTERIO-SCLEROSIS the tunica media, clue to a hypertrophy of its muscle fibres ; (2) a thickening of the tunica intima, clue to a hyperplasia of its subendothelial connective tissue, without atheromatous degeneration ; (3) in some instances fibrous hyperplasia and thickening of the tunica aclventitia. The muscular coat might show some degeneration, but the prevalent notion that in such thickened vessels the muscle of the middle coat was replaced by fibrous tissue, and so the seat of fibroid degeneration, was found to be entirely erroneous. These changes were not confined to limited areas of vessel wall, as in atheroma, but affected uniformly the whole length of the radial. They were found to be distributed through- out the body, the coronary and renal arteries, for instance, showing corresponding changes. The changes are shown in Figs. 9, 10, 11, 12, and 13. In Fig. 9 great thickening of the artery is shown, and is seen to be due to hypertrophy of the tunica media and some hyperplasia of the tunica intima. Fig. 10, a section of the kidney from the same case, shows, in the centre of the field, an artery with a much diminished lumen clue to fibrous hyperplasia of the tunica intima, while the tunica media is atrophied ; at a there is an occluded arteriole, Fig. 11 shows a small thickened radial artery, which was persistently small and hard during life. The thickening here is partly a hypertonic contraction, and in part, I think, the result of a hyperplasia of the adventitia. Fig 12, a section of the kidney from the same case, shows two arteries with their lumen encroached upon by hyperplasia of the tunica intima, while the tunica media is atrophied. Fig. 13 is a section of the trunk of one of the coronary arteries, showing hypertrophy of the media and hyperplasia of the intima. Here, as is sometimes found, there is also some atheromatous degeneration in the intima. The changes were often present when there was practically no atheroma in the aorta or the large arteries. They were, however, sometimes associated with atheroma of the aorta ; while atheroma of the cerebral arteries is so common in later life, that it, so far as my observations go, often accompanies arterio- sclerosis elsewhere. DISEASES OF ARTERIES The changes present in the kidneys are of great interest, for they seem to me to explain the confusion which still exists in relation to vessel and kidney changes in "granular kidney." The changes in the renal artery outside the kidney are as I have already described ; while the changes in its branches inside the kidney show a very important modifica- tion of, or divergence from, that description. I found that, inside the kidney, the arteries showed very marked fibrous hyperplasia of their internal coat, going on to complete occlusion of the vessel ; that the muscular coat as a rule atrophied and might practically disappear as the tunica intima thickened ; and that the external coat seemed to become denser from a proliferation of its fibrous tissue. As a result of these changes the transverse section of an artery, when occlusion was complete, showed like a fibrous globe, which might be indistinguishable from a fibroid glomerulus. The fibrous tissue might be of the hyaline variety with few nuclei ; and the change has consequently been sometimes re- ferred to as hyaline degeneration. A corresponding change occurs in the nutrient arteries of the brain, and possibly in other organs, which I have not, however, examined. Were this intimal thickening compensatory, in the sense thai Thoma and his followers apply the term, it would cease with the establishment of equilibrium. This, however, does not happen, the change going on to vessel occlusion. The changes in the kidney vessels have been much studied, and I have given a summary of the leading views propounded on the relations between the renal and vessel changes. It appears to me to be clear that error arose by applying the changes found in the arteries inside the kidney to all the arteries in the body. The first observer who recognised the true nature of the change in the tunica media of the systemic arteries was Dr. George Johnstone, who named it muscular hypertrophy, the reverse of the condition which occurred in the kidney ; while Gull and Sutton, looking at the intimal changes and at the kidney changes together, introduced the term arterio-capillary fibrosis. These observers made the mistake of applying their observa- tions on the kidney to the vessels generally. The result was, that in time the idea of a diffuse arterio-capillary fibrosis 24 Fig. 9.— Showing great thickening of radial artery. ---'' ,S;tv- Fig. 10. — Kidney from same case as Fig. 9, showing, in centre of field, artery with greatly thickened intima and atrophied media. At a, occluded arteriole ( x 50 diameters). CONCLUSION so dominated the medical imagination, that the thick arteries of chronic kidney disease were, as has abeady been mentioned, thought of as fibroid, if not as atheromatous ; and if fibroid of coiu'se hard and rigid ! The logic was sound, but unfortunately for truth the premises were wrong. To this sound logic with the faulty premises might, I think, be traced not a few of the prevailing misconceptions regarding circulatory phenomena ; but, attractive as this question is, I do not propose entering upon it here. It is necessary to revert to Johnstone's observations on hypertrophy of the muscular coat, for Savill in 1897 revived this on the strength of his own observations, and called the condition hyperniyotrophy. In a later communication he still more fully dealt with the importance of the muscular coat of arteries ; but the profession has shown no sign that it attached any practical significance to those observations or to the argument based upon them. In Savill's observa- tions there appears not to have been the thickening of the" tunica iutima which was usual in my cases. In only two of my first sixteen cases was there a pure hyperniyotrophy in the radial artery. This point has significance, for such arteries are clinically indistinguishable from those which have the intima thickened also ; and as the two conditions have corresponding causes I include both under the designation of arterio-sclerosis. CONCLUSION. The term Arterio-sclerosis would thus be applied clinically to all thickened vessels, other than those thickened Ijy atheromatous degeneration, and would include — («) pure hypermyotrophy, (&) hyperniyotrophy with thickening of the internal coat, and (c) those in which the adventitia was also thickened. For clinical purposes what is required is the. recognition of diffuse permanent thickening which is not atheroma. refeeencp:s. Ziegler, Leltrhuch cler Alhj. Spedellen Patlioloijischen Anatomie, p. 54. Thoma, Vircli. Arch., Bd. xciii. and cxvi. ; Pathology and Path. Anatomy, Eng. Trans., p. 247. Lancereaux, Arch. gen. de 25 DISEASES OF ARTERIES Med., 1893, i. pp. 5 and 164. Gueneau de Mussy, Aixh. gen. de Med., 1893, i. 23p- 5 and 164. Huchard, Maladies du Coeur et des Vaisseaux, 2 erne ed., Paris, 1893. Mott, System of Med., edited by Clifford Allbutt. Osier, Principles ajid Practice of Medicine, 2nd edition, p. 700. George Johnson, Med.-Chir. Transactions, vols. XXX., xxxiii., xlii., li., and Ivi., and Trans.^ Internal. Med. Cong., 1881. Gull and Sutton, Med.-GJiir. Transactions, vol. Iv. ; Trans. Path. Sac, vol. xxviii. ; Trans. Internal. Med. Cong., 1881. Dickinson, Diseases of the Kidney, 1875. Ewald, Dreschfeld, and Mahomed, Discussion, Trans. Internat. Med. Cong., 1881. Samuel West, Granular Kidney, 1900. Savill, Brit. Med. Journ., Jan. 23, 1897. I^othnagel. Specielle Pathologie und Therapie, Ed. xv., Erkrankungen der Gefasse L. v. Schrotter. W. Eussell, "Arterial Hypertonus and Arterio-sclerosis ; their Eelations and Significance," Lancet, June 1, 1901 ; Transactions, Medico-Chirurgical Society, Edinhurgh, vol. xx., 1900-1901 ; Encyclopcedia Medica, vol. xiii.. Article, "Vessels." Savill, Trans. Path. Soc. Lond., vol. Iv., 1904. John M. Cowan, Tlie Practitioner, Aug. 1905 and March 1906. 26 CHAPTER IV HYPERTONUS AND ITS CLINICAL RECOGNITION (a) IN XOX-THICKEXED AKTEPJES ; (b) IX SCLEROSED AETEPJES ; (c) IN ATHEEOMATOUS AETEEIES. HYPERTOXUS IX XOX-THICKEXED AETEEIES. A hypertonic vessel, as has been ah'eadj shown, is a vessel the muscular coat of which is unduly contracted. As a result of the contraction its diameter is reduced, its wall is thicker, and its lumen is smaller. The vessel to the finger feels thicker than the perfectly normal arterv, which is soft, thin- walled, and compressible. The degree of hardness varies of course with the amount of contraction. This increased thickness is very commonly mistaken for " sclerosis " or "atheroma," terms the significance of which has been already discussed. The thickening or hardness is commonly a uniform thickness, which can be felt in the radial arteries as far as they can be followed up the forearm. While this is the common character of a hypertonic artery, as revealed to the sense of touch, it has not always this characteristic. I have frequently noted that an artery, which turns out to Ije only hypertonically contracted, may feel as if it were made up of a series of thickened rings, or plates, or segments. An artery with these characters will almost certainly be regarded as atheromatous ; and it is only by knowledge and experience that one is prevented from giving a premature opinion, which may be totally wrong. I have observed these rings and plates to disappear rapidly under treatment directed to relieve vessel contraction. Thickened arteries, especially if they be 27 HYPERTONUS AND ITS CLINICAL RECOGNITION considerably thickened, as they may be, liave come to be looked upon as having undergone permanent structural thickening, for which nothing can be done, and which do not therefore call for further consideration from the clinician. There is of course no difficulty in determining when an artery, such as the radial or temporal, is thickened : the finger trained " to feel the pulse " has no difficulty, and there need be no dubiety in the mind of the observer as to the accuracy of his observations, for it is as easy to distinguish between degrees of thickening in arteries as it is in rubber tubes. With a little practice, once attention is drawn to the matter, the smallest degrees of hypertonus are recognised by the increase in the thickness of the wall of the artery. This varying thickness has escaped ol)servation, owing to so much attention having been given to the consideration of blood- pressure or of tension. Thickened arteries are recognised by all physicians, and are, as is well known, of common occurrence ; the real diffi- culty arises in determining whether the wall be thick from hypertonic contraction, true sclerosis, or perhaps even from atheroma. Atheroma is of relatively rare occurrence in the radial and temporal arteries ; its occurrence is confined to aged people, and is usually associated with areas of calcareous infiltration which are easily distinguished. Sclerosis is, on the other hand, common after middle life. Before middle life it is fair to assume that uniform thickening is mainly hypertonic, unless there be discoverable one or otlier of the two great causes of early sclerosis, namely, chronic kidney disease or syphilis, to which I think may be added a third, namely, the use of malt and other liquors. The size of the vessel aids in the differentiation : an ordinary sized or a some- what large vessel with a thick wall is usually structurally thickened ; a small vessel with a relatively thick wall is usually only hypertonic. Fig. 15 was taken from a section of an artery which, imtil a few days before death, was soft and unthickened. Some days before death it became definitely tightened up, and the figure closely corresponds with the impression made on the finger before death took place. 28 HYPERTONUS IN SCLEROSED VESSELS HYPERTONUS IN SCLEROSED VESSELS. The description of changes in sclerosed vessels, given in the preceding chapter, has prepared the way for the acceptance of a fact of great practical moment, namely, that sclerosed vessels retain their power of contractility. The significance of the retention of this movement has been so under-valued that it is hardly referred to in the extensive literature on the circulation. It is therefore all the more necessary to em- phasise the fact that arteries may be the seat of permanent structural thickening, while they are at the same time hypertonically contracted. As has already been stated in a preceding section, the idea of sclerosed and atheromatous arteries has hitherto carried with it the idea of rigidity. This is an unfortunate association, for it has led to the idea that thickened vessels are necessarily permanently thickened, that they behave in the body much as rigid tubes would behave, and that no remedial measures are available for re- moving such anatomical change. It is true that the structural changes in sclerosis are beyond therapeutic influence ; but the hypertonus which frequently accompanies it is well within the reach of such influences. When these contentions are accepted, it will be found that the presence of various symptoms lead to the diagnosis of the hypertonic factor in sclerosed vessels and to its appropriate treatment. Sclerosed vessels not only retain some measure of con- tractility, but it has seemed to me that they are abnormally responsive to some at least of the influences which determine arterial contraction. This seems to be the case particularly in old people. There is evidently a possible fallacy here, for in old people the eliminative processes are so impaired that the apparent increase of sensitiveness may be regarded, perhaps more properly, from this standpoint ; the quick muscular response only indicating a more ready saturation of the blood with such waste substances as act on the vessels, the response really remaining normal. For practical pur- poses, it is however of great importance to know that there is in most aged people this quick and ready re- sponse, and, when a measure of confidence is acquired in recognising hypertonic contraction, any dubiety that 29 HYPERTONUS AND ITS CLINICAL RECOGNITION may exist as to' the probability of such a sensitiveness will be lost. HYPERTONUS AND RELAXATION IN ATHEROMATOUS ARTERIES. As has been indicated in an earlier chapter the common conception of a sclerosed artery is that it is a rigid tube. This conception, as we have shown, was, borrowed from the teaching resardino; the vessels in advanced atheroma, and it is in accordance with experience that the extreme example be- comes the standard type. This common conception is, how- ever, erroneous, and seriously misleading. It is only in atheroma with much calcareous infiltration that the artery becomes practically a rigid tube. In my study of the arterial wall I have frequently been surprised to find the amount of relaxation that took place in a vessel that was clearly the seat of much calcareous infiltration. In other cases where, from the hooped and segmented character of the thickenings, there seemed little doubt that the thickenings were atheromatous, they could no longer be felt when the vessel became relaxed. In this latter class of case the character of the artery to the sense of touch is probably due to irregular thickenings of the intima plus hypertonic contraction, the thickenings not being felt when the w^all becomes soft, by the passing oft' of the hypertonus, or it may be due merely to irregularity in the muscular coat itself. In other cases the rigid segments persist, no matter what measures be taken for the removal of the hypertonic contraction ; and yet in a considerable number of such cases it is quite plain to the finger that a measure of relaxation can be eft'ected. That relaxation under such conditions occurs is due to the anatomical fact, that in atheroma it is rare for the entire circumference of the vessel to be aft'ected ; there is usually a considerable part of it where there is only moderate thicken- ing of the tunica intima ; and where the muscular coat can relax and contract so as to -appreciably affect the condition of the wall. The idea of the fixed and rigid tube has to be given up, save in extreme cases. That the recognition of such arterial changes is not due to a personal delicacy of 30 RELAXATION IN ATHEROMATOUS ARTERIES touch is proved by the fact that my hospital assistants and others, with whom I am brought into close association, readily acquire the skill, once their attention has been directed to individual cases and the significance of the phenomena explained to them. The condition of the arterial wall in advanced atheroma with calcareous infiltration has been shown in Figs. 5,6, and 7. Fig. 7 was taken from a patient with very stiff vessels, and yet I had no doubt that these vessels tightened up a little and relaxed a little under treatment. I may here refer to two cases illustrating this point, which made a special impression upon me, from certain associations. The first case, Mrs. M., aged 49, a patient wdio, simul- taneously with attacks of angina pectoris, developed motor paresis, had a radial artery which felt as if composed of hard segments, which were regarded as atheromatous, and yet this character entirely disappeared, the wall becoming uni- formly soft, under treatment which led to relaxation of the arterial wall. Whenever the vessel tightened up, it showed the same irregular thickening. This case is given in greater detail at p. 176. Case 1, an Irishman, aged 56, was admitted to Ward 3, for alcoholism. On admission, he was so restless and tremulous, that it was impossible to get an absolute record of his arterial pressure; it seemed to be considerably above 200. He soon quieted down, and he acknowledged that he had been drinking too much all his life, while for the last fifteen months his drinking was only limited by monetary barriers. He drank whisky and rum, and was amused at the suggestion that he had a preference for either, seeing he was so apprecia- tive of each. His right radial artery was thick and hard and marked by rigid segments, such a vessel as my clinical assistant spoke of as feeling so brittle that it gave one the idea that it would crack if it were fingered roughly. The pressure was 190. Under erythrol first, and then under iodide of potassium and squill, the vessel became larger and softer, and although the thickened segments were still perceptible they were not nearly so rigid, and the vessel lost that character which gave to it at first its brittle feel. Along with this change in the character of the vessel, the pressure 31 HYPERTONUS AND ITS CLINICAL RECOGNITION fell to 170. No one who followed the changes in this man's radial artery would have had any difficulty in being convinced of the accuracy of these statements. The effect on the vessel was produced hj physical rest in bed and abstinence from alcohol, but mainly by the action of the druo;s administered. CHAPTER V THE CAUSES OE HYPERTONIC CONTRACTION 1. INFLUENCE OF THE NEKA^OUS SYSTEM. 2. INFLUENCE OF THE COMPOSITION OE CONDITION OF THE BLOOD. 3. THE LOCALISATION OF THE ACTION ON THE VESSEL WALL. 4. INFLUENCE OF TOBACCO. Having dealt with hypertonic contraction as it occurs in normal, in sclerosed, and in atheromatous arteries, we next proceed to consider the causes which determine this move- ment on the part of the arteries. Let me again repeat that this property separates the arteries altogether from the vulgar mechanical conception which would make them mere elastic tubes. With regard to hypertonic contraction, the general ]3roposition may be submitted, that it is caused by one or other of two factors : First — The intluence of the nervous system. Second — The composition or condition of the blood. The converse of hypertonus is either a relaxation -of hypertonus or a diminution in normal or average tone. We may now consider, in some detail, the positive aspect of this subject, which is the more important, while not for- getting that the negative has an importance of its own. THE INFLUENCE OF THE NERVOUS SYSTEM. Taking up first the influence of the nervous system, it is universally known that the relations of the blood-vascular C 33 THE CAUSES OF HYPERTONIC CONTRACTION system to the nervous system have been traced and deter- mined by long and careful experimental investigation. The investigation of these relations has been so detailed, and the results have been so striking, that teachers, and through them students and practitioners, have almost come to regard the vessels as the toy of the nervous system, — that their manifestations merely mirror nervous influences. The effect of various emotions upon them was too apparent and too assertive to escape observation, or not to demand recognition. The path by which emotion travelled was traced, and the controlling power of the vasomotor centre in the medulla was determined. The result has been that the vaso- motor mechanism thus revealed has appealed so strongly to the medical imagination that the play or movement of the arteries has been thought of through the nervous system only : as if they had no identity, as if they were the mere weather- cocks of every gust of nervous influence, the bond-slave of the higher system. The nervous side of the vasomotor mechanism has been regarded as supreme ; as instigating, regulating, controlling, and determining all vascular phenomena, even those attendant upon the activities and exhaustions of organs and tissues. The names of Claude Bernard, Brown- Sequard, Waller, and Schiff are " household names " in this con- nection. I need not dwell at length on the achievements of physiological investigation in this department ; they are well known, and I have indicated that they have not hitherto been underrated. Their very brilliance has, I venture to think, seriously blinded us to the fact that physiological investigation has also shown that there is another factor which influences and determines the move- ment or play of the vessel wall ; that factor being the composition of the circulating fluid itself. It is with this factor that I mainly deal in these pages, and I hope to show that the failure to appreciate aright this aspect of the circulation has prevented our understanding many things ; while its recognition makes many things clear. I hope to show that the prevalent view is too exclusive, is incomplete, and correspondingly inaccurate and misleading. 34 INFLUENCE OF THE COMPOSITION OF THE BLOOD THE IXFLUEXCE OF THE COMPOSITION OF THE BLOOD It has l^een long known that a number of substances used therapeutically act directly upon the vessel wall, — that is, without the medium of the nervous mechanism, leading to contraction or relaxation of its muscular coat. Blake claims to have been the first to show that by injecting infusion of digitalis into the arteries contraction resulted. This observa- tion was made as long ago as 1839. Einger and Sainsbury's investigations are more recent, are widely known, and may indeed be regarded as having determined the views regarding the action of digitalis which we all hold. Their experimental investigations confirmed Blake's observation ; liut they further showed that digitalis acted independently of the nervous mechanism, acting directly upon the vessel wall. This was shown by isolating the vessels from their nerve supply. Donaldson and Stevens, experimenting with digitaliu, foimd that it caused constriction of the arterioles, probably through its action on the muscular coat. They further showed that it acted on the capillaries as well as the arterioles. Haynes, investigating the action of the digitalis group upon the heart, noted that although the coronary arteries are not innervated (sic), squill and digitahs cause some constriction of them, probably by irritant action. Dale, investigating the mode of action of ergot, has shown that the primary or stimulant action of this substance is a vaso-constrictor action, which is quite independent of the vasomotor centre. This investigation I shall have again to refer to. Experiment has further shown that if blood be mixed with aniyl - nitrite, chloral hydrate, morphine, quinine, or atropine, and made to pass through the vessels of a recently excised organ, dilatation of its vessels takes place : digitaliu and veratrin used in the same way cause contraction. Professor Halliburton, experimenting with choline, pro- duced by its means a temporary fall in arterial pressui'e, due in part to its action on the heart, Ijut mainly to dilata- tion of peripheral vessels, especially in the intestinal area. The action is due, he shows, to the direct action of this 35 THE CAUSES OF HYPERTONIC CONTRACTION sulistance ou the neuro -muscular apparatus of the vessels, the same effect being produced after the influence of the central nervous system was removed. Xeurine, on the other hand, causes peripheral constriction. From these alone it would seem as if Professor Leonard Hill were over-cautious in saying that " it is conceivable that the quality as well as the tension of the blood may be the exciting cause of vascular tone." It is quite clear that there is sufficient evidence to prove that the arterial and capillary walls can be stimulated to contract by the presence of substances in the blood acting directly upon them. Therefore the composition of the blood is more than " conceivably " a factor in maintaining, influencing, increasing or diminishing vessel tone. If we turn from the experimental side and inquire regarding the views held ou the clinical side, it will be found that there is a great mass of belief that substances present in the blood affect blood-pressure. Dr. Broadbent, later known as Sir William Broadbent, in his masterly little book on The Pulse gives capillary resistance as a cause of high tension, holds that certain substances in small quantities cause resistance, and mentions digitalis, ergot, carbonic acid, nitrogenous waste, and the products of imperfect metabolism as examples of such action. Broadbent, of course, knew that some at least of the substances enumerated caused contraction of arterioles and capillaries, and yet his words suggest to me that he thought of modifications in the composition of the blood as causing difficulty in its passage through the capillaries rather than of the difficulty being caused by capillary or arteriole contraction. The conception of altered composition, of something added to the Idood, rendering its flow more difficult through the peripheral vessels, is practically the same view as is expressed in the term " increased viscosity," the view towards which Professor Clifford Allbutt definitely leans, wdiile his philosophic mind and wide practical experi- ence do not allow him to wholly adopt it. However attractive the idea of increased viscosity may be, it is necessary to realise that there is no convincing evidence that deleterious substances, such as clinically may ^.6 INFLUENCE OF THE COMPOSITION OF THE BLOOD be assumed to l^e present in the blood, so affect its \dscosity or specific gravity as to impede its flow through the arterioles and capillaries. In cholera certainly, and probably in other conditions with great intestinal flux, the blood becomes so inspissated as to seriously impede its flow : but in such a condition as chronic interstitial nephritis, that there should be anything approaching this state is a very different matter. With a free supply of fluid it is difficult to think of the viscosity of the blood, thereby meaning its specific gravity, being seriously modified, seeing that fluid is so readily taken up and discharged from it. Huchard holds that excess, and above all errors, in alimentation, throw toxic substances into the blood which produce a state of spasm of the arterial system, followed by hyper-tension and arterio-sclerosis. Senator and many others hold corresponding views with regard to the importance of the presence of nitro- genous waste products in the blood. The general conception undoubtedly is that " nitrogenous waste, and the products of imperfect metabolism," to repeat Broadbent's words, when present in the blood, raise blood- pressure. It is not necessary to elal^orate this point further ; the literature of kidney disease, and more recently of blood-pressure, is full of it, not to go further afield for examples. The explanation of the raised blood-pressure has usually been referred to increased peripheral resistance, and there the matter has as a rule been left ; although, as has been said, critical and accomplished physicians hke Broadbent and Allbutt have seen that this term in the ecjuation wants determining, while to others the phrase in itself has been all-satisfying. My contention is that certain suljstances present in the blood, even in small cj^uantity, cause arterial and capillary contraction. This is the fundamental fact, and will be found to be the first step in all raising of blood- pressure which goes on to arterio-sclerosis. Even a slight degree of such contraction means peripheral resistance. There is indeed no need to go beyond vascular contraction for the explanation of peripheral resistance ; it is the simj)lest explanation, as it is the most certain factor, and, 37 THE CAUSES OF HYPERTONIC CONTRACTION be it remembered, not necessarily brought about through the nervous system. As the capillaries contract as well as the arteries, the " stop-cock " theory of Dr. George Johnstone must yield to the more prosaic view that arteriole contraction is but part of a wider contraction, and is not a special arrangement for saving the capillaries. If we are to retain any part of this attractive conception, it will require to be so modified that arteriole and capillary contraction may be regarded as a provision for diminishing the supply of an impure blood to the tissues. This is really a truer conception, for it is the good of the tissues which is the aim of the circulation, and this vessel constriction not only protects directly, but also indirectly, by producing symptoms which can lead to what we may call blood purification. The mechanical views of the circulation have had their day, and have effected their purpose almost too well ; it is now time that we should think of the vessels as living tubes, contracting not only under the influence of nerve centres, but under the direct stimulus of substances present in the circulating blood — contraction so caused being the liypcr- tonus and the hypertonic contraction of our argument as much as when it is a response to nerve impulses. THE LOCALISATION OF THE ACTION ON THE VESSEL WALL The fact that arterial contraction can Ije determined by blood composition, or by l^lood-content, has, as has been already said, but little influenced practical medicine. It is therefore all the more necessary not only to show, as I have just done, that the proposition is supported by the weight of physiological investigation, as surely as the action of the sympathetic nervous system is established, but to see how much further physiological investigation and experiment will allow us to go. It will be seen that experimental investigations still further warrant and support our clinical contentions ; and they ought, I think, to satisfy and convince those who have hitherto thouQ-ht of vessel contraction and of blood- LOCALISATION OF ACTION ON VESSEL AVALL pressure only or mainly from the side of the vasomotor nervous mechanism. The point which I think it is so desirable to consider is what Elliott speaks of as " the localisation of the action " of the substances which have been experimented with ; that is, the particular element or part of the vessel wall which, when stimulated, leads to contraction, although the vaso- motor nerve connections are severed. The point has been investigated by means of adrenalin, the action of which as a vaso-constrictor is well known. The work of Oliver and Schafer, Langley and others in this country, of Cybulski, Boruttau and others on the continent, have fully established the possession of this remarkable action on the part of this substance as obtained from the suprarenal glands. Lewandowsky, investigating the action of adrenalin, sug- gested that its action on plain (unstriped) muscle simulated that which follows on electrical stimulation of the sympathetic nerves supplying the special part being examined. Langley followed this up, and showed that the extent of contraction of the blood vessels in the various organs varied with their control by vasomotor nerves. ElKott has still further sustained and elaborated the preceding investigations. The conclusion at which he arrives is as follows : " The reaction to adrenahn of any plain muscle in the body is of a similar character to that following excitation of the sympathetic (thoracico-lumbar visceral, or autonomic) nerves supplying that muscle, and the extent of the reaction varies directly with the frequency of normal physiological impulses received by the muscles in life through the sympathetic nerves." As regards the action on the blood vessels, he says that " the parallel action of the sympathetic nerves and of adrenalin is main- tained in the heart and blood vessels." This constriction is produced in the largest arteries as well as in the arterioles. It is not evident in the veins. Erom Exner and Melzer's experiments by intraperitoneal injection it seems more than probable that the capillaries, at least in certain regions of the body, are also constricted by adrenalin. The fact of constriction being thus established, the question necessarily arises, does the adrenalin act through 39 THE CAUSES OF HYPERTONIC CONTRACTION the vasomotor nervous mechanism or upon the vessel wall ? These, as in the case of the heart, may be regarded respect- ively as the neurogenic and the myogenic views. That the stimulation is produced at the periphery was proved by Brodie and Dixon, who found that the vaso-constrictor nerves to the limbs lost their electrical irritability within three hours of death, while the vessels reacted to adrenalin six hours after death. Degeneration of the sympathetic nerves after section does not hinder the action of adrenalin upon the vessels. These investigators located the point of stimulation in the " connecting link between nerve fibre and muscle fibre, . . . which is not necessarily a constituent part of the muscle fibre, nor yet of the nerve fibre," and they designate it " neuro-muscular junctional tissue." Elliott's comment on this is that " when plain muscle develops connection with sympathetic nerves, it must at the myoneural junction acquire a mechanism that can receive the nervous impulse " ; further, " adrenalin excites not the muscle fibre directly, but a substance developed out of it." He repeats and amplifies this as follows : " The irritability of the muscle toward adrenalin depends on the differentiation of part of its substance to form the myoneural junction. And it has been shown that the sensitiveness of reaction depends on the frequency with which it receives sympathetic nervous impulses in the reflexes of daily life. Once, however, the sensitiveness has been developed, it does not in the life of the individual become dulled by the total abeyance of arriving impulses, such as, for instance, is caused by degen- erative section of the nerves. Then, indeed, the junction acquires an exaggerated irritability." This, however, does not exhaust the interest of this subject. Another experimenter, Mr. H. H. Dale, in a most important study of the action of ergot, has shown that its primary action upon the circulatory system is stimulant, — that is to say, that it leads to contraction of the vessel w^all, this being the well- known vaso-constrictor action which has led to its use as a therapeutic agent in practice. This vaso-constriction leads, of course, to a rise of blood-pressure in the aorta, and is held by this observer to be quite independent of the vasomotor centre. Although the vaso-constrictor action of ergot is as widely 40 LOCALISATION OF ACTION ON VESSEL WALL known as anv fact in medicine, it is certainly not equally known that there is a further action, brought about bv larger doses, which is its secondary or paralytic action. That is to say, large doses of ergot lead to dilatation of vessels instead of to constriction. When ergot has been used in sufficient quantity to produce this effect upon the vessel the vessel no longer responds to the application of adrenalin : that is, adrenalin can no longer constrict it. The action of the ergot is to paralyse the myoneural junctions on which, as has been already shown, adrenalin acts. With the paralysis of the junctions the constrictor effect of stimulating the sympathetic is also lost. There is another gland in the body, which, as Ohver and Schiifer have shown, produces a substance which has a like vaso-constrictor action to adrenalin — the gland being the Pituitary Body, or rather its infundibular portion. The con- strictor or pressor principle in this gland produces its stimulant effect directly on the arterial wall, not on the vasomotor nervous mechanism. Yet the remarkable fact has been chsclosed by Dale, that ergot in large quantity does not neutralise its action, as it neutralises the action of adrenalin. Dale says that the constrictor or " pressor principle contained m pituitary extracts produces its stimulant effect on the arterial muscle, not through any part of the sympathetic nervous apparatus, not through the related structures on which adrenalin acts, but through some other substance or substances of the muscle fibres themselves." It is therefore plain and evident that vessels constrict by the direct influence of substances in the blood. The conception which has so long dominated our views, and it is hardly too much to say sealed our eyes, that vessel contraction or relaxation, or the associated alterations in blood-pressure, are the manifestations of nervous impulses, has to be given up in great part, and must share its honours with tlie other factor. While the direct influence of constrictor substances on the vessel wall is thus established, it is to be noted how subtle the processes are : adrenalin acts upon what is neither nerve nor muscle, but is euphoniously termed the myoneural junction : pituitary extract acts on the vessel wall as adrenalin does, not, however, upon nerve, nor upon the myoneural jmiction, but upon some substance which, as it is none of the things mentioned, 41 INFLUENCE OF TOBACCO is assumed to be muscular. Choline acts in the same way, but its action can be prevented or neutralised by atropine. How futile seem the controversies regarding the neuro- genic or myogenic origin of vascular response ! How many controversies have been waged over alternatives, when each was but part of a more central truth ! THE INFLUENCE OF TOBACCO In Chapter XV., which deals with angina pectoris, it is pointed out that one of the recognised clinical varieties of the affection is the toxic form. I illustrate this form by reference to the effect an overdose of tobacco may have on myself. The cardiac discomfort accompanying the hypertonic con- traction noticed in the radial artery illustrates what is perhaps the mildest form of angina pectoris that can be experienced. It is, however, difficult to determine through which system tobacco acts, so I give it this special paragraph here. Tobacco is much used, and its influence upon the vessels has definitely attracted the attention of clinicians. Personally I have not so far paid any special attention to it, but my clinical assistant. Dr. J. L. Green, has recently made observations on himself and a friend. He tells me that if he or his friend inhales a cigarette made of Virginian tobacco, the hypertonic contraction of the radial artery which ensues is very marked, and that with the liardening of the vessel the heemomauometer reading rises 15 mm. Hg. Here, as in other instances, the fact is the constriction of vessels. What the blood-pressure may be inside the constricted vessels is a proUem dealt with in other chapters. REFERENCES. Halliburton, Biucliemistry of Muscle and Nerve, 1904, p. 119 et seq. H. H. Dale, Journ. of Physiol., vol. xxiv. No. 3. Donaldson and Stevens, Journ. of Physiol., 1881, vol. iv. Landois, Physiology, 10th ed., 1904. Broadbent, The Pulse. Leonard Hill, Schafer's Phystoloriy. Elliott, Journ. of Physiol., 1905, vol. xxxii. p. 401. Senator, Folia Therapeutica, A])n\ 1907, p. 37. Oliver and Schafer, Journ. of Physiol, vol. xviii., 1895, pp. 230 and 277. Schafer and Vincent, ibid., vol. xxiv. p. xix. 1899. Brodie and Dixon, ihicl., vol. XXX., 1904, p. 494. Langley, ihid., vol. xxxiii., 190.5-6, p. 374. LeAA^andowsky, Arch,, f. Anat. u. Physiol., 1899, p. 360. Ringer and Sainsbury, Med. Chi. Trans., vol. Ixvii. Haynes, Bio- Chemiccd Journ. vol. i., Feb. 1906. 42 CHAPTER VI THE CLINICAL ESTIMATION OF BLOOD-PRESSURE 1. AETEEIAL TENSIOX AND BLOOD-PKESSUEE. 2. METHODS OF ESTIMATING BLOOD-PEESSUEE. 3. THE FAGTOES WHICH DETEEMINE H^MOMANOMETEE EEADINGS. ARTERIAL TENSION AND BLOOD-PRESSURE. Foe many years the attention of clinicians has been largely directed to what has been called " arterial tension." The significance to be attached to the term has been variously interpreted ; its relation to blood-pressure has been dis- cussed by Professor Clifford Allbutt and others. In its everyday and ordinary use there is no doubt it has been associated with much confusion of idea and serious error. Allbutt, with his critical faculty, decides that the word " tension " is practically not applicable to the blood inside the vessel, and with this I entirely agree. If it is not to be referred to the l_ilood, it might be assumed that it is applicable to the vessel wall. It is not, however, proposed to attempt to discuss the various shades of meaning the word " tension " may have, — that may Ije left to the pundits in physics. And yet I cannot leave the matter without express- ing my belief that the term was used by our most expert clinicians to express not blood-pressure, nor thickness of vessel wall, but the relationsliip between blood and wall — the sustained fulness of the vessel, and so forth. More recently, attempts have been made to do away with the term " arterial tension." The present writer Was amongst the first to definitely propose this, but it is almost impossible to get a familiar word given up. Others have met 43 THE CLINICAL ESTIMATION OF BLOOD-PRESSURE the difficulty by maintaining that the terms " tension " and " pressure," are synonymous. Personally I hold that \Yhatever conduces to clearness of thinking is desirable, so I am quite ready to accept this definition of the terms, but I do not think that it is correct historically. It seems to me that our best clinicians meant more than this indicates, that to them there was a living and active relationship between the state of the vessel wall and the volume of blood inside it. Dr. Leonard Williams, in a lecture delivered at the Medical Graduates College, says : " High arterial tension is an expression which is used as a synonym for ' high blood-pressure,' than which it is more euphonious, but less correct." While believing, as I do, that our ablest clinicians meant more than is here implied, the meaning of words is frequently modified, and it would greatly simplify the position were the term " tension " to be given up, or definitely used as synonymous with " blood- pressure." In the examination of the pulse two factors are com- monly considered, no matter what terms the observer uses to express his mental concept, namely, the condition of the arterial wall and the blood-pressure inside it. Putting aside for the moment the first of these, the estimation of the pressure within the artery is undoubtedly taken as the index of the power of the heart. The " strength " of the pulse has no meaning clinically, save as an index of heart power. A " feeble " pulse means to the chnician a feeble heart ; a " strong " pulse the reverse. That the pulse can reveal this is the warrant for " feeling the pulse," which is the custom of the clinician. The effect of the blood-pressure upon the arterial wall could, I presume, be expressed in terms of " degrees of tension," and it was the cultured appreciation of this which, I believe, marked the skill of our ablest physicians ; but it can easily be that the acquisition of this skill is now regarded as too difficult, for the internal pressure, whatever it be, is exercised upon tubes which vary in thickness of wall, in size of lumen, and in the relation of wall to lumen. The term " tension," unless only used as a somewhat rough indicator, has thus a very subtle significance. Another aspect of this question may l)C referred to, 44 ARTERIAL TENSION AND BLOOD-PRESSURE namely, the not uncommon use of the term " high tension " to thickened radial arteries. This confusion arose from the teaching that high blood-pressure and thickened arteries went together ; so, when the arteries were thickened the pulse was frequently spoken of as of high tension. Of course, this error was not universal, for it was widely recognised that in thick radials there might l^e a feeble pulse of low blood- pressure. I refer to this because it is by recognising how error originated that it is most readily rectified. Senator, in a recent lecture on arterio-sclerosis, says that in his experience an increase in arterial tension is a very inconstant factor, and depends greatly upon the condition of the heart ; while the rigidity of the arteries places a serious obstacle in the way of determining the conditions of pressure within them. Thickening of the arterial wall no doubt adds to the difficulty of estimating the blood-pressure ; but it is, I think, not so difficult as is the estimation of wall tension. As it is blood-pressure, in the sense in which it has just been indicated, which is the main object aimed at when the pulse is examined, it materially helps if this single conception be kept before the mind, and all thought of " tension " be abandoned. That the finger can be educated to a high degree of proficiency in determining blood-pressure there can be no doubt. What has to be acquired is the power to estimate the pressure inside tubes of different sizes, and with walls not only of different but of varying thickness. As we learn - to dis- tinguish between large and small objects, as we distinguish between a thick - walled and a thin-walled tube of equal circumference, so we learn to judge of the flow of fluid through tubes. There is nothing more subtle or mysterious in it than this, iDut it probably requires a delicate flnger and much careful self-education. Could we introduce a cannula into a patient's artery, and connect it with a manometer, a record would be obtained which would check observations made by the finger, and provide a record the accuracy of which would not be questioned. As this cannot be done, methods have been devised and instruments have been constructed with the object of providing such records. In all skilled work ingenuity is constantly directed to devise means of 45 THE CLINICAL ESTIMATION OF BLOOD-PRESSURE eliminating the individual equation : in the particular matter with which we are deahng it would be of value to be able to do this. It would be of still greater value could an electrical balance be devised that would correctly weigh and estimate the data upon which a diagnosis is based, so that the individual judgment and the personal mental bias would be eliminated. We are, however, far from this, and after we have counted blood corpuscles, estimated htemoglobin richness, determined blood specific gravity, found the total nitrogen excretion, taken sphygmographic tracings, used the most recent of " blood-pressure " instruments, and piled up a goodly array of clinical data, the final judgment may be no whit better. The personal equation cannot be eliminated in diagnosis, and when it is all-important to form a correct estimate of the circulation as a whole, our most recent methods still leave the decision to the individual acumen and experience ; to what is nothing else than the skill of the individual, determined by inherent mental faculty, developed by education and en- riched by much accurate observation. METHODS OF ESTIMATING BLOOD-PEESSURE. We may now proceed to examine the methods in use for the clinical determination of blood-pressure, to note some of the contentions based upon the records so obtained, to determine what data the methods used really supply us with, and what practical use can be made of the data which they supply. I have no special desire to pull down if I cannot at the same time build afresh, but it is more than time that this important subject were put upon a sound foundation, and that the errors with which it threatens to be surrounded, it might even be said adorned, should if possible be checked. This is not mere hyperbole, for the present position is not only curious but undesirable. The position is this ; on the one hand may be placed the physiologists who have accepted the instruments in use, and believe that they give an accurate --record of blood-pressure ; along with them there are a certain number of physicians who have accepted the dictum of the physiologists, and have drawn important clinical inferences from the risfid application of physiological methods 46 " -. - METHOD^S OF ESTIMATING BLOOD-PRESSURE to pathological conditions. On the other hand, there ai'e a number of physicians who have absolutely discarded the instruments in question, not only as useless, but as seriously misleading. When this is the state of opinion, it is evident that there is something to be found out, and the matter is so very important from the physician's standpoint that I do not hesitate to submit my observations and conclusions, in the belief that they can and ultimately will reconcile divided opinion. The plan or principle on which blood-pressure instru- ments are based is simple, and may be briefly described. An armlet made of some strong material has a rubber bag attached to its internal surface. When this armlet is applied and fastened by means of straps, the rubber bag is blown up by means of a ball syringe attached to the bag by rubber tubing ; another piece of rubber tubing leads to a manometer which records the pressure of the air inside the apparatus as it is slowly pumped in. When the bag of the armlet is distended sufficiently to grasp the arm, the index of the manometer moves up and down with every arterial pulse wave : at a certain pressure the pulse wave, as seen on the index of the manometer, attains its maximum degree of excursion ; this point is taken by some observers to repre- sent the diastolic loressurc in the arteries. Other observers use the same kind of instrument in another way, — the bag of the armlet is distended until the arterial circulation in the arm is stopped by the pressure of the distended bag, the stoppage being judged of by the finger on the radial artery, or by a second bag attached to a wristlet. The height to which the manometer index has risen is taken as representing the maximum or systolic pressure. A third method is applied in the construction of Gartner's tonometer and corresponding instruments. In this method one of the fingers is rendered bloodless by passing a tight rubber ring from the tip of the finger upwards along the two terminal phalanges, then a rubber bag is passed round the proximal phalanx and distended with air sufficiently to ensure sufficient compression to pre- vent blood passing into the finger after the rubber ring is removed ; the pressure in the bag is recorded by a manometer attached to it hj a rubber tube ; the pressure is slowly 47 THE CLINICAL ESTIMATION OF BLOOD-PRESSLTRE lowered, and the point at wliich the index stands when the finger flushes is taken as the systolic pressure. In the first method the maximum pulsation obtained from the compressed vessel is taken as the record; in the second and third methods the point at which the vessel or vessels are so obliterated as to arrest the circulation in the part is taken as the record. It is these records which it is maintained give the " blood - pressure." After using and comparing various types of instrument in a variety of cases it seems to me that those which are used to obtain systolic pressure by Dr. Geoi'o-e Oliver's hfemomanometer as made by Mr. Hawksley, 357 Oxford Street, London, W. A detailed description of the instrument and hov-- to use it is supplied by the maker. means of obliterating the brachial artery, or its branches in the upper part of the forearm, are the most satisfactory. They are mostly modifications of the Eiva-Eocci instrument. Personally I prefer Dr. George Oliver's modification for two reasons : first, because in the manometer a spirit index is used instead of mercury, which makes it more easily carried about : and second, because it has a wrist bag by means of which you can see when the pulsation in the radial artery stops, which is less of a strain upon the attention of the observer than using the finger, while those around the patient can have the whole proceeding demonstrated to them, which is impossible when the observer can only communicate what his finger determines. By the methods which have Ijeen described it is apparent 48 METHODS OF ESTIMATING BLOOD-PRESSURE that when, for example, the armlet is applied to the upper arm, pressure is exerted by the air-pad upon all the soft tissues of the arm, sufficiently to compress the brachiar artery, so that by obliteration of its lumen the pulsatile movement is arrested on the distal side of the compression. It is surely reasonable to claim that this can Ije expressed as com- pressiMlity, and that the soft tissues take some share in the result ; but above all, it would seem reasonable to assume that the physical characters of the artery will materially influence the result. That it is compressibility which is determined cannot really be denied ; and this being so, it is a matter of common knowledge that the compressibility of a tube depends upon the thickness of its wall, and the relation l)etween that and the size of its lumen. A large tube with a thick wall is more easily compressed than a small tube with the same thickness of wall. And yet, plain as this may appear to be, it is taught that the compressibihty of an artery is determined wholly by the pressure of the blood inside it, that the thick- ness or thinness of the wall is a negligible factor, and that there- fore the compressibility, as measured by the htemomanometer, is literally " blood-pressure." Janeway, in his well-known book on blood- pressure, definitely states his view as follows : " That a sclerotic vessel may offer considerable resistance to compression is a common beUef which I do not think is justified." It is unnecessary to single out others by name, for it will be found in most recent writings that compressibihty has been assumed to be " blood-pressure,"^ — no other explanation or interpretation of records has been given, so far as my reading has revealed. No doubt, as Janeway says, there is a " common belief " which is contrary to this, but the object of writers on blood-pressure seems to be either to ignore it or to assume that it is one of the common leliefs which possess the minds of uninformed persons. Although the condition of the arterial wall is so definitely assumed to be a negligible factor in the records obtained by means of the htemomanometer, it must be remembered that, before the instruments referred to came into such extensive use, it was fully recognised by the best clinicians that the state of the vessel wall was an important D 49 THE CLINICAL ESTIMATION OF BLOOD-PRESSURE factor in what was commonly known as " compressibility of the pulse." It was, indeed, universally recognised that when the wall was thickened the pulse was less compressible. If the new conception were correct, it would imply that what was formerly regarded as knowledge was a mere figment of the imagination, and that all our knowledge about thin and thick tubes appertained to the physical characters of rubber tubes, and had no relationship to the arterial tube. The revolutionary nature of the newer view seems to have been but partially realised. It seems to have been based upon' observations on normal walled vessels, for I cannot imagine anyone accustomed to the clinical observa- tion of arteries, and equally familiar with the appearance of the same vessels after death, accepting the new view. It is as unsound pathologically as it is clinically. If the wall of an artery can become many times thicker than the normal, the common physical law must be applicable to it, — '- it cannot but be more resistant, it cannot but require more powder to obliterate its lumen. The normal radial artery, for instance, collapses by its own weight when empty, while it is commonplace knowdedge in pathology that if the wall of an artery is thickened its cut end gapes. Certain physical pro- perties are as applicable to arteries as to rubber tubes. It is indeed curious to note, on the one hand, the application of the physical characters of rubber tubing to illustrate and elucidate the phenomena of the circulation ; and on the other hand, the apparent abandonment of all our common knowdedge of physics when the compressibility of an artery is imder consideration. As the result of experience, I venture to say that when the method of obtaining hpemomanometer readings is submitted to the physicist, he will smile at the suggestion that the readings represent the pressure of the fluid inside the compressed vessel. This point need not be further elaborated, and I willingly turn from it to the constructive side of the subject. THE FACTORS DETERMINING H.^:iiIOMANOMETER READINGS I submit that, by the methods used, the light of a limited knowledge of physics suggests that there are three 50 HvEMOMANOMETER READINGS factors to be considered — (1) The soft tissues surrounding the artery ; (2) the arterial wall : and (3) the pressure of the blood within it. Tissues surrounding the Artery. — Taking up the first of these — -the soft tissues surrounding the artery — I may at once state that so far as I can see this factor is practically negligible. I thought at one time that it might prove to be an important factor, but after a careful comparison of the girth of arms, whether due to muscularity or adiposity on the one hand, or to emaciation on the other hand, with manometer readings, I am convinced that the factor is, as I have said, practically negligible. Even the appUcation of the pressor bag over the arm covered with ordinary clothing gives mucli the same record as when appKed over the uncovered arm. Further, the bag on the upper part of the forearm gives practically a like reading to that obtained from the upper arm. I therefore pass from this factor to the consideration of the other two. Thickness of Arterial Wall. — That the thickness of the wall of a tube, and the proportion this bears to the bore, affects its compressibihty is a fact of common knowledge, as has been already pointed out. It is one of the beliefs it is difficult to reaUse should require proving. That the contrary opinion exists, when the tubes are arteries, has been already shown ; and it seems to me that it has arisen by the rigid application to clinical and pathological problems of the conclusions drawn from physiological experiment and observation. It has come about in this way. A normal artery of such size as the radial has such a thin wall that, when empty, it collapses, as a piece of thin rul^ber tubing collapses ; if the vessel be full of blood, or other fluid, its walls are held apart, and its lumen is maintained. If by any device fluid pressure is exerted on the outside of this full vessel a very small extra pressure will lead to its collapse. Xo matter what the pressiares be, the result is, I believe, the same. The wall is practically, if not theoretically, negligible. That similar results have been obtained with arteries which have undergone what I have defined as arterio-sclerosis is to be explained by the entire loss of tone in the dead vessel, so that it is no longer comparable to the living vessel. 51 THE CLINICAL ESTIMATION OF BLOOD-PRESSURE There is, of course, no doubt that the arteries we examine clinically vary enormously in the thickness of their wall, and the relation of thickness of wall to bore. There are, however, no records of the results of the examination after death of radial arteries known to be thickened during life. Pathologists and clinicians in the post-mortem room have gone to the aorta or the cerebral arteries in search of atheroma, and have left the vessel felt during life undisturbed in its resting place, and overlooked even amidst the yearnings of clinical curiosity. This was formerly my own position, but in 1 9 1 I drew attention to the gravity of the omission ; and what I wrote then and subsequently is the outcome of obser- vations which are almost monotonous in their uniformity. The difference in the thickness of radial arteries and in the relation of thickness of wall to bore has been shown in Figs. 9 and 11, and is further represented in Figs. 14, 15, 16, 17, 18, 29, and 80. There is no question here of post-mortem rigidity, and the influence of fixatives ; these arteries felt after death as they had felt during life, save for the absence of pulsation in them, so that the only question is what changes led to their thickening ? These changes I have described in an earlier chapter. No fixative treatment of normal arteries will produce such pictures as I have given. Professor Mac- William found that arteries taken from amputated limbs were by stimulation so altered that their diameter could be reduced to one-third, with, of course, a corresponding thicken- ing of the wall. This is a wide range of contractility in a normal vessel, yet in arterio-sclerosis, where the thickening encroaches upon the lumen, and contractility is retained, the diminution is still greater. Some of my cases have shown a thicker wall and a smaller bore than MacWilliam records. I cannot but think that those who have thought that the vessel wall was negligible have not had the data necessary to a correct opinion. The following chapters will illustrate the part taken by the vessel wall in haBmomanometer observations. It is, however, necessary to repeat what has been said earlier, that thickness of the arterial wall may be due to two factors, separate' or combined, namely, permanent structural thickening and hypertonic contraction ; 52 2 sp -5 ^ „ so oT