OBSERVATIONS on the PATHOLOGY of PERIPHERAL Postgrad Med J: First Published As 10.1136/Pgmj.22.245.75 on 1 March 1946

OBSERVATIONS ON THE PATHOLOGY OF PERIPHERAL Postgrad Med J: first published as 10.1136/pgmj.22.245.75 on 1 March 1946. Downloaded from VASCULAR DISEASE (Exclusive of congenital malformations and neoplasms) By WILLIAM BLACKWOOD, F.R.C.S.E. (From the Scottish Mental Hospitals' Laboratory, The Royal Infirmary, Edinburgh, and the Department of Pathology, Universitv of Edinburgh.) Introduction mediate between those of large calibre and (3) The Although the circulatory system cannot properly arteries of medium calibre (e.g. radial) (Fig. I), be considered except as a whole, there is such an which comprise the majority of the macroscopically abundance of pathological conditions to which it visible arteries in the body. They regulate the is subject, in whole or in part, that limitations of flow to the major and minor regions of the body. space alone demand that it be divided into parts In their media the elastica is less, being generally and that only a part be considered here. This limited to an internal and external elastic lamina. paper will therefore be confined to the peripheral (In the cerebral vessels the external elastic lamina vascular system, which is arbitrarily defined as all is absent.) Unstriped muscle is however present the circulatory system exclusive of the heart, in large amount and, by response to autonomic aorta and pulmonary system. For a similar nervous impulses, can produce wide variations in reason it is proposed to omit the consideration of calibre. As in the large arteries the {fibrous vascular malformations and neoplasms. adventitia contains the small vasa vasorum through which blood is conveyed to most of the media. The intima and inner layers of the media are Anatomical, Physiological and General nourished by the blood in the lumen of the vessel Considerations itself, either directly or possibly through internal The purpose of the blood vessels is to conduct vasa vasorum. Serious local disease of theseProtected by copyright. blood in the right quantity to the right place at vessels and the resultant ischaemia can often be the right time and it is at the capillary level that overcome by means of collateral circulation, the metabolic i.nterchanges occur. The demands through unaffected protions of the vascular tree. of the tissues vary greatly from time to time, e.g. (4) The arterioles (e.g. afferent renal glomerular muscles in action require a greater blood flow arterioles) (Fig. 2), which are chiefly muscular in than those at rest. Such intermittent demands construction and have but little elastica. The for large quantities of blood are met by means of a calibre of the arterioles is an extremely important capillary bed of variable size. Economy of work factor in the general arterial blood pressure. In and conservation of heat are effected by diminishing the voluntary muscles the calibre of the vessels the blood flow by vascular constriction, pre- (possibly of all sizes) is controlled largely by local dominantly at the arteriolar level. metabolites. (Barcroft et al, I943.) Elsewhere These functions of the vascular system are it is controlled by the autonomic nervous system. associated with appropriate anatomical structure. A "pressor" substance, hypertensin (angiotonin), (i) The arteries of large calibre (e.g. aorta, inno- is now known to influence the calibre of thehttp://pmj.bmj.com/ minmate, subclavian) which convey blood easily to arterioles and its action is thought to be directly all parts of the body, have a smooth endothelial upon the muscle of the vessel wall. lined intima which confines but does not appre- (5) The capillaries have walls consisting only of ciably impede the flow of blood: a thick media endothelial cells and an outer fibrous perithelium. composed of fibrous and elastic tissue, fibrous It is at this level that metabolic exchange occurs. tissue for strength and elastica for storing the They are liable to damage from circulating toxins dynamic energy of each cardiac systole and for and when pre-stasis or stasis of blood occurs they releasing it during diastole, and so prolonging the are the point at which plasma and erythrocytes on September 26, 2021 by guest. forward impulse to the blood: and a connective may leak out of the circulatory system (Fig. 3). tissue adventitia. Their structure does not allow In the acral subcutaneous parts of the body them to vary much in calibre and serious inter- provision is made for by-passing the capillaries by ference with their integrity has very dangerous. means of (6) Arteriovenous anastomoses. These consequences for the individual. Syphilis (pro- are richly innervated vessels with thick walls ducing aneurysms), atheromatous degeneration composed chiefly of modified muscle cells. Amongst (not usually to a degree to cause serious obstruc- the functions ascribed to these shunts is that of tion) and mechanical trauma (producing dissecting thermo-regulation. They do not suffer from any, aneurysm, traumatic aneurysm, haemorrhage, etc.) as yet known, specific disease processes, apart from are the commonest agents in diseases of these vessels. neoplasia. The large arteries merge into (2) The atteries of (7) Venules and veins (Fig. i). These vessels mixed type (e.g. common iliacs) which are inter- convey the blood back to the heart. Lined by 76 POST-GRADUATE MEDICAL JOURNAL March, 1946 Postgrad Med J: first published as 10.1136/pgmj.22.245.75 on 1 March 1946. Downloaded from endothelium, the wall is composed of elastica and B. Due to Chemical Trauma or Circulating Toxins. plain muscle and of relatively more connective Ergotism. tissue than in an artery. The distinction between Glomerulo-nephritis. the media and the adventitia and between veins C. Due to Mechanical Trauma. of various sizes is not sharp. They are controlled Arterial concussion, contusion Venous contusion and by the autonomic nervous system. Disease of the and laceration. laceration. Periarterial haematoma and Spontaneous venous veins does not usually have such severe conse- false aneurysm. thrombosis (of the quences as that of the arteries, with the possible Traumatic arteriovenous com- axillary vein). exception of pulmonary embolism. Two distinct munication. Femoral venous throm- systems of veins, the systemic and portal systems Bland embolism. bosis. are known. These systems communicate at certain D. Due to Thermal Trauma (cold). well-known regions, at which the veins may Raynaud's disease and the become engorged in portal obstruction. Recently Raynaud Phenomenon. the importance of the paravertebral and spinal Immersion foot or Trench foot. veins has becomerecognised in the explanation of the Frostbite. spread of emboli to the spine from the viscera E. Due to, or Associated with, Increased Intra- without involvement of the lungs, e.g. bony meta- vascular Pressure. stases from prostatic carcinoma. (Batson, I940). Diffuse hyperplastic sclerosis: Varicose veins. (a) of arteries, Haemorrhoids. The Effects of Vascular Disease (b) of arterioles (fibrous, hyaline and necrotic). The effect of vascular disease is frequently to Massive cerebral haemorrhage. produce some degree of ischaemia in the field of distribution of the diseased vessels. The degree F. Of Uncertain or Unknown Aetiology. of ischaemia will depend upon the degree of Chronic arterial disease: Thrombo-phlebitis

(a) Monckeberg's medial migrans. Protected by copyright. narrowing of the arterial lumen, upon the site or sclerosis, sites of narrowing, upon the degree of collateral (b) Atherosclerosis. circulation, the degree of associated vasospasm, Thrombo-angiitis obliterans -upon the way in which the available blood is (Buerger's disease). shared out amongst the different tissues, upon the Rheumatic arteritis. metabolic demands of the tissues, upon the rate Periarteritis nodosa. at which the ischaemia develops and upon its duration. In the limbs the effect of vascular obstruction are generally:-(i) diminution of the pulse, (2) lowering of the skin temperature, (3) a A. Diseases Due to Bacterial pale or cyanotic skin colour, (4) pain, (5) glove or Infection stocking anaesthesia. Structurally there may be: Pyogenic organisms.-Vessels passing through (i) generalised atrophy or necrosis, (2) nerve or adjacent to a focus of pyogenic infection may degeneration. In muscle ischaemia necrotic muscle show acute inflammation of the wall-an acute http://pmj.bmj.com/ may be replaced by fibrous tissue, Volkmann's bacterial arteritis or thrombophlebitis. Thrombosis Ischaemic Contracture (Griffiths, I940). is the usual sequel, especially in veins. Septic emboli may arise from the heart (e.g. ulcerative Classification endocarditis) and become impacted in a small Medical nomenclature and classification being artery, cause secondary infection and weakening still debatable subjects the opportunity is taken of the wall with the formation of a mycotic aneurysm of classifying upon an aetiological basis. The 4 and (Figs. 5). on September 26, 2021 by guest. word arteriosclerosis, unqualified, is deliberately Syphilis.-In the aorta syphilitic disease of excluded, for it is too general, and too compre- the vasa vasorum and damage to the elastica are hensive in meaning. the main features. In the arteries of medium Diseases of the Systemic Peripheral calibre, especially in the brain, the condition is a pan-arteritis. The organism is present in the Vascular System vessel wall and the severity or tempo of the reaction varies. Sometimes the condition is associated Arterial, Artcriolar and Venous with much necrosis, a gummatous arteritis, some- Capillary times necrosis is slight or absent and there is well marked concentric intimal fibrosis, minimal damage A. Due to Bacterial Infection. to the elastic medial Acute bacterial arteritis. Thrombophlebitis. internal lamina, slight replace- Tuberculous arteritis. Pylephlebitis. ment fibrosis, adventitial fibrosis and infiltration of Syphilitic arteritis. all coats by lymphocytes and plasma cells (Fig. 6). PERIPHERAL VASCULAR DISEASE WM. BLACKWOOD, F.R.C.S.E. 77 Postgrad Med J: first published as 10.1136/pgmj.22.245.75 on 1 March 1946. Downloaded from Illustrations

FIG. I.-Control posterior tibial vessels from a case without FIG. i8.-Traumatic arteriovenous communication, of four vascular disease. The artery (larger vessel) shows the inter- months' duration. Shell wound of occipital artery and nal elastic lamina, the muscular media and the narrow internal jugular vein. The section has been made in the adventitia with contained external elastic lamina. The plane of the fibrous communication (C) uniting artery (A) vein (smaller vessel) contains less elastic, less plain muscle, and vein (V), after the vessels have been opened up. H. & E. more fibrous tissue. Elastic van Gieson stain x 23 x 4. (N.P. 2334.) (N.P. 2IOO). FIG. I9.-Higher power view of part of Fig. I8. The normal FIG. 2.-Glomerulus and afferent glomerular arteriole () muscularis and elastica of the vessels come abruptly to an from a case without renal disease. H. & E. X 250. (N.P. end, the artery and vein being united by well vascularised 2890.) cellular fibrous tissue, the surface layers of which form an FIG. 3.-Fat embolism. Cerebral capillary haemorrhages in a intact endothelial lining to the communication. Upon the patient who was knocked down by a bus four days before arterial side fibrous tissue has grown over the surface of the death. Thick frozen section in which blood is stained by arterial intima for a short distance. Elastic van Gieson- Pickworth's method. x 30. (N.P. 2574.) stain. X 20. FIG. 4.-Mycotic aneurysm. Intracerebral haemorrhage from FIG. 20.-Traumatic arterio-venous communication. Median middle cerebral artery (->) in which septic embolus from cubital vein on proximal side of brachial arterio-venous subacute bacterial endocarditis of aortic valve had impacted. fistula of two years' duration, showing hypertrophy of all (N-P. I257.) mural elements (compare Fig. I). Elastic van Gieson FIG. 5.-Mycotic aneurysm. Cerebral artery with impacted stain. X 24. (N.P. 2074.) infected embolus from a case similar to that in Fig. 4. At FIG. 21.-Traumatic arterio-venous communication. Hyper- one point ( t ) the arterial wall is giving way. H. & E. x 8o. trophied and dilated heart in the case of a 22-year-old (N.P. 370.) Courtesy of Prof. J. R. Biggart. traumatic fistula between profunda femoris artery and FIG. 6.-Syphilitic arteritis (cerebral vessels). There is well femoral vein. Courtesy of Dr. A. R. Gilchrist. marked concentric intimal fibrosis, minimal damage to the FIG. 22.-Raynaud's disease. Secondary organic fibrous internal elastic lamina, slight medial replacement fibrosis narrowing of the digital artery in a woman, aet. 32, with a and infiltration of all regions, but especially the adventitia,

nine years' history. Elastic van Gieson stain. x 75.Protected by copyright. by lymphocytes and plasma cells. H. & E. x 40. (N.P. Courtesy of Prof. J. R. Learmonth. II84.) Courtesy of Dr. A. C. P. Campbell. FIG. 23.-Diffuse hyperplastic arteriosclerosis (renal interlobular FIGS. 7 and 8.-Tuberculous arteritis in tuberculous leptomenin- artery). There is concentric intimal fibrosis, concentric gitis showing predominantly mononuclear infiltration of all reduplication of the internal elastic lamlna and fibrous coats. Subendothelial infiltration (E) is a characteristic replacement of the media. Elastic van Gieson stain. feature. H. & E. x 6o & x 350. (N.P. 1285.) X 250. (R.I.E. 557/39.) FIG. 9.-Acute glomerulo-nephritis. The glomerulus shows proliferation and swelling of the capillary endothelial cells FIG. 24.-Diffuse hyperplastic arteriolosclerosis (renal afferent and there is an infiltration with polymorphonuclear leuco- glomerular arteriole), showing fibrous mural thickening. cytes (compare Fig. 2). H. & E. X 250. (C.B. iii.) Compare Fig. 2. H. & E. X 250. (R.I.E. 557/39.) FIG. io.-Subacute glomerulonephritis. Reticulin and collagen FIG. 25.-Hyaline change in renal afferent glomerular arterioles have been laid down between cells and loops of the now in a case of arterial hypertension. H. & E. X 250. lobulated glomerulus, whilst proliferation of cells lining FIG. 26.-Arteriolonecrosis (renal afferent glomerular arteriole) Bowman's capsule has produced a characteristic "crescent." showing the necrotic change characteristic of malignant H. & E. X 250. (D.B. 4789.) hypertension. H. & E. X 250. FIG. II.-Chronic glomerulo-nephritis. Fibrous replacement FIG. 27.-Chronic arterial disease (posterior tibial vessels). The and atrophy of the glomerular unit are occurring. H. & E. artery (larger vessel) shows intimal fibrosis with recanalised X. 250. (D.B. 30I2.)

mural thrombus, eccentric splitting of the internal elastic http://pmj.bmj.com/ FIG. I2.-Arterial contusion. Mortar bomb injury to axillary lamina, medial degeneration with calcification (black) and artery 24 hours previously. The lumen is distended with minimal adventitial and venous change. Elastic van recent thrombus. The wall shows (4-) severe damage to Gieson stain. X 22. intima and media. H. & E. X I2. (N.P. 2075.) FIG. 28.-Atherosclerosis (basilar arterv) showing eccentric sub- FIG. I 3.-Arterial contusion. Section of arterial wall from endothelial fibrous thickening with fatty change in the region ; in Fig. I2, showing severe damage to media and deeper part, eccentric splitting of the internal elastic lamina intima. The adventitia is relatively intact. Elastic van and fibrous replacement of medial muscle. Masson's Gieson stain. x 8o. trichrome stain. x 30. (N.P. io84.) FIG. I4.-Arterial contusion. Section of arterial wall from FIG. 29.-Thromboangiitis obliterans (posterior tibial vessels). region in Fig. 12, showing media and intima infiltrated The artery (larger vessel) shows t recanalised intimal throm- on September 26, 2021 by guest. by red blood cells and polymorph leucocytes. A portion bus, little damage to internal elastic lamina, slight medial of the internal elastica has become separated and lies in the fibrosis and much adventitial fibrous tissue increase, binding luminal thrombus. H. & E. x 8o. together the artery and the similarly affected vein. Many FIG. I5.-Arterial laceration. One month ago lateral wound of of the clear apertures in the media are dilated vasa-vasorum. brachial artery. Now organised partly recanalised throm- Elastic van Gieson stain, X 22. (E. H. 6oo B.) us fills both the aperture (A A1) and the lumen (L) of the FIG. 30.-Polyarteritis nodosa. Renal interlobular arteriole, vessel. H. & E. x I5. (N.P. 2298.) from a case following sulphonamide therapy, showing acute FIG. I6.-Post-traumatic aneurysm. Bisected sac of aneurysm degenerative or necrotic change in the vessel wall and pre- of acromio-thoracic axis, five months after shell wound. dominantly polymorphonuclear (often eosinophile) leuco- The white rod passes along the lumen of the artery and can cytic intramural and peri-vascular infiltration. H. & E. be seen through the wound in the wall. The sac consists of X 250. (E.H. 498 A.). the organised periphery of the haematoma. Courtesy of FIG. 3I.-Polyarteritis nodosa in stage of healing (vessels in Prof. J. R. Learmonth. epineurium of median nerve). The artery shows marked FIG. 17.-Traumatic arterio-venous communication, eight intimal and slight adventitial fibrosis: the vein is healthy. months after a shell wound of the popliteal vessels. A H. & E. x 85. (N.P. 2553.) small aneurysmal sac (S) forms part of the communication. Figs. I, 27 and 29 are reproduced by permission of the author Courtesy of Prof. J. R. Learmonth. and of the Editor of the Edinburgh Medical Journal. ~itj78 PERIPHERAL VASCULAR DISEASE WM. BLACKWOOD, F.R.C.S.E. Postgrad Med J: first published as 10.1136/pgmj.22.245.75 on 1 March 1946. Downloaded from

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0%.21 Mawrch, I946 PERIPHERAL VASCULAR DISEASE 79 Postgrad Med J: first published as 10.1136/pgmj.22.245.75 on 1 March 1946. Downloaded from Tuberculosis.-Arteries in the neighbourhood Arterial injury may be classified as (a) Concussion of a tuberculous focus may. become involved. or arterial stupor, where there is no primary The process is most clearly seen in the leptomen- histological evidence of damage. (b) Contusion inges where characteristic changes occur in tuber- where the damage is often more severe in the culous leptomeningitis. There is a mononuclear inner coats of the vessel than is apparent from infiltration of all coats, especially below the endo- without. The damage may extend widely within thelium and there is sub-endothelial connective the vessel from the point where the surface indi- tissue proliferation (Figs. 7 and 8). cation is most obvious (Figs. I2, I3 and 14). (c) Laceration including complete division. All B. Diseases Due to Chemical Trauma or these conditions may be associated with peripheral Circulating Toxins vasospasm, which may be relaxed if the damaged Ergot, a fungus Which grows on rye, has long segment is removed. been infamous for its effect upon the plain muscle Thrombosis is a common sequel of arterial injury of the arteries and its ability to produce ischaemic and is even more marked in damaged veins. It necrosis. Lewis (I935) has shown that, in the may spread distally, it may wholly or partly cock's comb, the reduced blood flow through the obstruct the lumen, it may seal off a hole in the peripheral capillaries produces severe nutritional vessel wall (Fig. I5). Later the clot may contract disease of the wall. Plasma leaks out in association rendering the lumen once more patent or allowing with stasis and necrosis in the tissues with retrograde blood to leak out of a lateral wound. Thrombosis is thrombosis of larger vessels complete the picture. followed by organisation andpossible recanalisation. Acute glomerulo-nephritis, from which the sub- When an artery is completely divided, if it is acute and chronic phases may develop, is a disease not a large one, then it is usually sealed off by which may follow bacterial infection (scarlet fever) prompt contraction and retraction of the inner and it is now thought to be an allergic response. coats. Thrombosis occurs and there is endothelial This allergic response may be considered as mani- and subendothelial proliferation at the injuredProtected by copyright. festing itself throughout the body, but it is most site and finally organisation. conspicuous in the capillaries of the glomerular It is lateral wounds, or wounds involving almost tuft, where slowing of the blood stream is associated the whole of the arterial circumfereince, which with endothelial hyperplasia, sometimes with give rise to most complications. In these wounds polymorphonuclear leucocyte infiltration and loss there is much haemorrhage into the peri-arterial of albumin and red cells into the periglomerular tissues producing a peri-arterial haematoma. This space (Fig. 9). In the subacute stage the proli- is followed by a marked inflammatory reaction in ferative phases of the inflammation are present. both the damaged arterial wall and the sur- Reticulin and collagen are laid down between cells rounding tissues. The associated oedema accounts and loops, respectively, of the glomerular capillaries, for much of the swelling at this time. It helps to whilst the lining cells of Bowman's capsule proli- limit the haematoma, but it would hinder explora- ferate to form the characteristic "crescent" tion by the surgeon. The peri-arterial haematoma (Fig. io). In chronic glomerulo-nephritis replace- first coagulates peripherally, limiting the spread of http://pmj.bmj.com/ ment fibrosis of damaged tissue is the chief feature haemorrhage. It may press upon the main or (Fig. II). collateral vessels. The haematoma may develop The above are but examples of the many condi- into a false aneurysm, the aneurysmal sac being tions in which blood vessels show a greater or excavated in the haematoma by the pulse wave. lesser degree of reaction 'to the presence of Ultimately the sac has a wall of laminated clot circulating toxins, foreign proteins and abnormal lined interually by endothelium and with an outer chemical substances. fibrous wall (Fig. i6). The wall of the sac is thickest at the point most distant from the arterial on September 26, 2021 by guest. C. Disease Due to Mechanical Trauma wound, thinnest close to the wound; indeed, shortly Blood vessels may suffer direct severe trauma after injury, the wall nearest to the wound is so from a penetrating wound by a bullet, with the thin and lightly adherent, that the whole aneurysm risk of the introduction of foreign bodies or bacteria: may easily be swept off the adventitia. Sur- from crushing; from stretching or tearing in rounding structures, especially nerves, may be association with the fracture of adjacent bones. included in the wall of the sac. These aneurysms They may suffer repeated minor traumata, e.g. may undergo spontaneous cure, though usually at the hiatus tendineus in adductor magnus, or they tend to enlarge. They usually develop soon in the case of the classical popliteal aneurysm of after the injury but development can be delayed. postboys. The structures primarily involved may When this occurs it is probably due to the be either artery, vein or nerve, or any combination spontaneous yielding of a partly healed arterial of these. wound. on POST-GRADUATE MEDICAL JOURNAL March, I946 Postgrad Med J: first published as 10.1136/pgmj.22.245.75 on 1 March 1946. Downloaded from Secondary haemorrhage usually occurs in with slowing of the blood stream and a rubbing the first two or three days or again seven to ten together of the devitalised intima in the collapsed days after injury. The latter is the more serious. veins of the calf (Boyd, 1942) leads to thrombosis. It is due to a defect in the localisation of the The thrombus is not in itself so serious, but a haematoma, some part of the limiting boundary large portion is apt to become detached and give of the clot giving way. This may be due to infec- rise to a massive pulmonary embolism. After tion of surrounding tissues, to a rise of blood pregnancy and abdominal operations, when there pressure consequent upon increased general has been some element of sepsis and when the activity, to movement, or sometimes to the thrombosis is widespread in pelvic and femoral giving way of the thin line of union between the regions, the condition of phlegmasia alba dolens, small aneurysmal sac and the wall of the arterial "whiteleg" may occur. wound. Infection of the haematoma itself is rare. Traumatic Arteriovenous Communications. D. Disease Due to Thermal Trauma When, as the result of mechanical trauma, there is a communication between the blood flow in an (Cold) artery and the blood flow in a vein, the condition Physiological mechanisms are present in our is either one of aneurysmal varix, where there is bodies which enable us to withstand reasonable direct communication between artery and vein: and individually variable degrees of chilling. The or varicose aneurysm, where the communication chief physiological mechanism is that of vaso- includes a false sac (Fig. I7). constriction of peripheral vessels, especially Such lesions are often produced by an object arterioles. In some people there may be an passing either between the artery and vein, or exaggeration of this response and they then going right through them from side to side. In exhibit the Raynaud phenomenon, or, if in women, the second type of injury the perforation in the in the hands and bilaterally symmetrical, Ray- vein, on the side remote from the artery, readily naud's disease. It is a condition of intermittent Protected by copyright. heals. A varicose aneurysm may not show for abnormal spasm of the digital arterioles in response days or weeks. This gradual formation may be to cold. In its early stages it is not associated due to delay in the canalisation of the initial with any particular structural change but later periarterial haematoma or because thrombus was there may be secondary organic intimal fibrosis present in the vein and blocked the wound. (Fig. 22). The sequelae of a traumatic arteriovenous If loss of heat from the extremities is accelerated communication are both local and systemic. The by prolonged exposure to a moist cold atmosphere sac of the aneurysm does not tend to increase in then the condition of immersion foot or trench foot size, because the vein acts as a safety valve for the occurs. With long continued arterial and arteriolar arterial pressure. An endothelial lining grows spasm there is ischaemia and dilatation of the over the connecting passage (Figs. i8 and I9). capillary bed: plasma escapes through the damaged There is proximal dilatation and distal narrowing capillary walls leading to oedema of the extra- of the artery, whilst the vein dilates, becomes vascular tissues and to a consequent "conglutina- http://pmj.bmj.com/ tortuous and its wall becomes hypertrophied and tion" or increased concentration of red blood cells arterialised (Fig. 20). Centrally, as a result of within the capillaries (Kreyberg, I945). Some the constant leak of blood out of the arterial tree damage, partly from ischaemia, partly from cold, there is enlargement and hypertrophy of the heart occurs in the surrounding tissues. When the (Fig. 2I). There is a normal systolic but a reduced patient reaches a warmer environment the arteries diastolic blood pressure. If the fistula is occluded and arterioles relax, blood returns to the part and the diastolic blood pressure rises and the pulse the local temperature rises. More plasma may rate slows. There is an increase of blood volume. leak out of damaged vessels. In capillaries where on September 26, 2021 by guest. Nutritional changes, distal to the communication, the red blood cells are "conglutinated" it may be are miimal. difficult for blood flow to recommence and pre- A condition of some raritv is spontaneous stasis or stasis may develop. Such stasis and thrombosis of the axillary vein. Ffrench (I9944) consequent ischaemia will, in a warm environ- has suggested that this aseptic thrombotic process ment, rapidly cause much more tissue damage and is due to exercise, which produces a sudden rupture necrosis. This is the danger point in immersion of small tributaries draining into the axillary vein foot and is thought by Kreyberg to be the mechan- and that this rupture leads to thrombosis, which ism of the greater part of the tissue damage. The spreads to the axillary vein itself. vessels in immersion foot show but little change A more common condition is thrombosis in the and thrombosis is not a feature except in regions ilio-femoral veins. A period of forced recumbency, of necrosis or secondary infection (Blackwood, with angulation of the femoral vein over the pubis, I944). PERIPHERAL VASCULAR DISEASE WM. BLACKWOOD, F.R.C.S.E. 81 Postgrad Med J: first published as 10.1136/pgmj.22.245.75 on 1 March 1946. Downloaded from

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R11E |S,.s.....X...... | ..... X i - ~-zi,p March,' 1946 PERIPHERAL VASCULAR ffISEASE Postgrad Med J: first published as 10.1136/pgmj.22.245.75 on 1 March 1946. Downloaded from If the part is chilled to below -50C. then the renal interlobular arteries show concentric frostbite develops. Here, again, stasis of'- blood subintimal fibrosis, roughly concentric splitting occurs. With return to a warmer environment of the internal elastic lamina, well marked medial an inflammatory response appears, with blistering thickening partly due to muscular hypertrophy and sloughing of dead tissues. Thrombi are now but chiefly to fibrosis (Fig. 23). The picture is found in the arteries and veins of the skin and sub- one of work hypertrophy with subsequent failure cutaneous tissues, both in the necrotic regions and and replacement fibrosis. In the arterioles -the in those adjacent (Lewis, I941). Obliterative change, first seen in the afferent glomerular endarteritis.is reported to occur proximal to the arterioles of the kidney, consists of fibrous thicken- necrotic region (Ducuing, d'Harcourt, Folch and ing with narrowing of the lumen (Fig. 24). Bofill, I940, quoted by Bigelow, I942). In frost- Fibrinoid degeneration often occurs, the arteriolar bite as in immersion foot a state of vaso-neuropathy wall becoming much thickened and having a and cold sensitivity may develop and last for a structureless hyaline eosinophilic appearance long time. (Fig. 25). The characteristic lesion of malignant In high altitude frostbite where the temperatures hypertension is that of arteriolo-Lnecrosis, where are very low, Davis, Scarff, Rogers and Dickinson the vessel wall shows necrotic changes with; conse- (I943) found that, in the hands, the initial imme- quent haemorrhage, superimposed upon the lesion diate response is constriction of the terminal of fibrinoid degeneration (Fig. 26). Fibrous portions of the superficial arterioles. Damage to thickening will be visible if the "malignant" the endothelium of the terminal cutaneous capillary hypertension was preceded by-a period of "benignl" loops results, after exposure, in transudation of hypertension. fluid or there may be thrombosis at the arteriolo- Massive Cerebral Haemorrhage.-A common capillary junction. These changes produce larage cause of death, in arterial hypertension, is massiVe blisters. VWhen the exposure is more severe and cerebral haemorrhage. It occurs generally in- theProtected by copyright. the deeper arterioles are damaged, then dry basal ganglia or pons, where the blood supply is gangrene results. Concentric intimal fibrosis of from short rather large arteries, which come off the digital arteries proximal to severe cutaneous at right angles from their large parent trunks. lesions is reported as a sequel. The pathogenesis is in dispute, but it is probably not due to the rupture of an atheromatous vessel E. Diseases Due to or Associated under a high pressure, -nor to the rupture of Charcot miliary aneurysms (really adventitial with Increased Intravascular Pressure haemorrhages). It may be due to the rupture Primary or essential hypertension, the com- of a vessel whose supporting tissues have died monest type of hypertension, is now thought to from the ischaemia of intermittent vasospasm be due to the production, by the kidney, of a (Globus, I938) or it may be due to the confluence pressor substance called renin, which unites with of haemorrhages from capillaries, whose walls, hypertensinogen in the blood plasma to form damaged by anoxaemia during vasospasm of the hypertensin. This reaction is subject to the feeding arteriole, cannot contain the blood which http://pmj.bmj.com/ presence of an antipressorsubstance hypertensinase, rushes into them when the arteriolar spasm also elaborated by the kidney. relaxes. Hypertension is associated with contraction of Hypertension in veins of the portal system pro- the muscle of small arteries and arterioles. It is duces haemorrhoids. In the systemic system it is not yet certain which is the primary factor -in usually seen in the lower limbs in the form of essential hypertension-the production of a pressor varicose veins. Here there is a strong element of

substance or some degree of vascular abnormality hereditary weakness of the veins. The- venous on September 26, 2021 by guest. or disease. walls lack elastic tissue, they stretch easily, and In benign hypertension of some duration and in when the valves are thus rendered inconripetent malignant hypertension, structural changes are the whole long column of blood can exert its found in the small arteries and arterioles of the pressure. The veins become varicose and. con- kidneys and often of liver, pancreas, suprarenals, siderable perivascular fibrosis occurs. Thrombosis gastro-intestinal tract, spleen, muscle, retina and, is common, calcification may occur. to a lesser extent, in the brain. If the hypertension is benign and of some duration, then the vascular changes are partly hyperplastic and partly dege- F. Diseases of Uncertain or Unknown nerative. If malignant the changes are degenera- Aetiology tive and may be necrotic in character. Chronic Arterial Disease.-This is a disease The changes are those of diffuse hyperplastic usually occurrmg in the elderly of both sexes'and sclerosis. After hypertension of some duration, in diabetics. In the extremities, especially' the 86 POST-GRADUATE MEDICAL JOURNAL March, 1946 Postgrad Med J: first published as 10.1136/pgmj.22.245.75 on 1 March 1946. Downloaded from lower extremities, the change is 'usually- that of gical findings during the acute stage are similar Monckeberg's medial sclerosis, where the vessels to those seen in the acute stage of thrombo- show focal regions, often rings, of medial calcifi- angiitis obliterans. cation (sometimes even of ossification), and slight Rheumatic Arteritis.-Von Glahn and Pappen- intimal fibrosis (Fig. 27). Often superimposed heimer (I926) described a focal disease of peripheral upon this is atherosclerosis which, by itself, .is a arterioles and capillaries which was present in disease both of the aorta and larger limb vessels, association with rheumatic heart disease. The but also of the cerebral, coronary and intestinal active lesions were characterised by necrotic vessels. It consists primarily of a fibrous sub- changes in all layers of the vessel wall and an endothelial thickening of the intima. Fatty-change infiltration of fibrin, polymorphonuclear leucocytes is common in the deeper part of the plaque, calci- (occasionally eosinophile) and large mononuclears fication may occur and haemorrhage here may into the vessel wall and surrounding tissue. suddenly occlude the vessel. Thrombosis may Vessels were also seen undergoing healing with occur upon the damaged intima. The internal recanalised connective tissue obstruction of the elastic lamina usually shows eccentric splitting lumen. They considered it to be distinct from and may be increased in amount. Fibrous replace- periarteritis nodosa, which it closely resembles ment of the medial muscle may occur. The except for the absence of thrombosis, but it is adlventitia is usually unaffected (Fig. 28). doubtful if this opinion can now be upheld. The aetiology of these conditions is still in Periarteritis nodosa is an acute or subacute doubt. They occur in regions of pressure or focal inflammatory disease of medium and small strain. Loss of elasticity of the muscularis and arteries. It affects vessels in all parts of the degenerative changes in the elastica are both body so that biopsy of muscle may be used as a changes occurring normally with increasing age. diagnostic procedure. Macroscopically the vessels

Winternitz (1938) demonstrated the presence of show nodular swellings up to pea size, those ofProtected by copyright. vasa vasorum, especially those given off from the very small size being the commonest. Histolo- lumen and suggested that, in response to unknown gically, in a flamboyant case, there is necrosis of toxic or bacterial agents, these vessels might show of the media and intima, including the intimal exudative changes (including haemorrhage) or elastic lamina; there is infiltration of all coats proliferative changes and that upon this basis of and especially the perivascular region by neutro- tissue reaction rests the aetiology of atherosclerosis. phile and eosinophile polymorphonuclear leucocytes Thromboangiitis obliterans (Buerger's (Fig. 30). Thrombosis and aneurysmal formation disease) is a disease of young male adults, affecting occur. Though generally progressive, local healing one or more segments of the vascular tree, occurring may occur with fibrous replacement of the damaged most frequently in the lower limbs. In the early vessel wall (Fig. 3I). It is a disease of all ages stages there is acute inflammation of the wall and but more common in early or middle age. The perivascular tissues of both artery and vein with presence of eosinophile leucocytes in the exudate polymorphoniclear leucocytic infiltration. Throm- has always suggested an allergic aetiology. Rich bosis occurs within the vessel and is subsequently (I942) noticed the occurrence of the condition http://pmj.bmj.com/ organised and recanalised. At the edge of the following therapeutic administration of serum and thrombus Buerger (I924) saw miliary foci not of sulphonamides. He has been able to produce unlike "tubercles." the condition in rabbits by injection of horse At the stage when it is usually seen there is serum and considers the disease to be a mani- medial and adventitial fibrosis, involving and festation of anaphylactic type hypersensitivity. binding together both artery and its accompanying

vein. The internal elastic lamina is not parti- The author wishes to express his gratitude to on September 26, 2021 by guest. cularly damaged. The lumen of both artery and Professor A. M. Drennan for his helpful criticism, vein contains organising thrombus which may be to various gentlemen for permission to use photo- extensively recanalised. The vasa vasorum are graphs, and to Mr. T. C. Dodds for the micro- prominent and may afford a local collateral path- photographs of the majority of the sections, which way (Fig. 29). There is sometimes an associated were prepared by the technical staffs of laboratories element of spasm. The aetiology is unknown. in the Royal Infirmaryand Universityof Edinburgh. In its early stages the condition is either asso- REFERENCES ciated with or may be preceded by thrombophlebitis The following publications were consulted in the preparation of this migrans, a migrating superficial phlebitis of the article. BARCROFT, H., BONNAR, W. M., EDHOLM, 0. G., and EFFRON, extremities. A short portion of a vein becomes A. S. (I943), "On Sympathetic Vasoconstrictor Tone in Human Skeletal Muscle," J. Physiol., 102, 2I. tender, swollen and reddened; in a few weeks the BATSON, 0. V. (1940), "Function of Vertebral Veins and Their Role in inflammation subsides and then migrates to another Spread of Metastases," Ann. Surg., 112, I38. BEATTIE, J. M., and DICKSON, W. E. C. (I943), A Textbook ofPathology part of the same or a different vein. The histolo- (Wm. Heinemann, Medical Books Ltd., London). March, I946 A NEW TEST FOR PREGNANCY Postgrad Med J: first published as 10.1136/pgmj.22.245.75 on 1 March 1946. Downloaded from BIGELOW, W. G. (2942), "'Modern Conception and Treatment of Frost- MAXIMOW, A. A., and BLOOM, W. (1938), A4 T'extbook of Histology bite," Canad. M.A.J., 47, 529. (W. B. Saunders Coy., Philadelphia). BLACKWOOD, W. (1944), "Pathologist Looks at Ischaemiiia," Edin. M.J., PICKERING, G. W. (I943), "Circulation in Arterial Hypertensioni," 51, 131. Brit. M.J., 2, I and 31. BLACKWOOD, W. (I944), "Studies in Pathology of Human 'Immersion KREYBERG, L. (I945), "Soine Notes anid Considerationis Regardinlg Foot,' " Brit. J. Surg., 31, 329. Injuries fromii Cold. io8th (U.S.) General Hospital (to be published). BOYD, W. (I942), Surgical Pathology (W. B. Saunders Coy., Philadelphia). LEARMONTH, J. R. (I943), "Reflex Vasodilatation in Surgery," Edin. BUERGER, L. (1924), The Circulatory Disturbances of the Extremities, M.J., 50, I40. incltuding Gangrene, Vasomotor and Trophic Disorders (W. B. Saunders LEARMONTH, J. R., BLACKWOOD, W., and RICHARDS, R. L. Coy., Philadelphia). (1944), "Localised Arterial Thrombosis of Indeterminate Origin," CLARK, W. E. Le Gros. (I945), The Tissues of the Body (Oxford University Edin. M.J., 51, I. Press, Oxford). LEWIS, T. (935), "Maniner in Which Necrosis Arises in Fowl's Comiib DA-VIS, L., SCARFF, J. E., ROGERS, N., and DICKINSON, M. (I943), Under Ergot Poisoning," Clin. Sc., 2, 43. "High Altitude Frostbite," Surg. Gynec. and Obst., 77, 561. LEWIS, T. (1941), "Observations on Some Normnal and Iisjuriouis Effects DUCUING, J., d'HARCOURT, J., FOLCH, A., and BOFILL, J. (1940), of Cold Upon Skin anid Underlying Tissues," Brit. M.J., 2, 795, 837, "Les troubles trophiquies des extr6mit6s produiits par le froid sec 869. en pathologie de guerre," J. de chir., 55, 385. RICH, A. R. (I942), "Additional Evidence of Role of Hypersenisitivity FFRENCH, G. E. (I944), "Spontaneous Thromiibosis of Axillary Vein," in Etiology of Periarteritis Nodosa; Anlother Case Associated with Brit. M. J., 2, 277. Sulfonamide Reaction," Butll. Johns Hopkins Hosp., 71, 375. GLOBUS, J. H. (I938), "Massive Cerebral Haemiiorrhage," Proc. Ass. RICH, A. R., and GREGORY, J. E. (1943), "Experinmental Deilsonlstra- Res. Nerv. Ment. Dis., 18, I937, 438. tion that l'eriarteritis Nodosa is Manifestation of Hypersetnsitivity," GRANT, R. T. (I940), "Observations on Periarteritis Nodosa," Clin. Sc., Btll. Johns Hopkins Hosp., 72, 65. 4, 245. VoN GLAHN, W. C., and PAPPENHEIMER, A. M. (1926), "Specific GRIFFITHS, D. L. (1940), "Volkimianoi's Ischaendiic Conitracture," Brit. Lesions of Peripheral Blood Vessels in Rheiumatismn," Am. J. Path. J. Surg., 28, 239. 2, 235. MAKINS, G. H. (I9I9), Gunshot Injutries to the Blood Vessels (Johii WINTERNITZ, Al. C., THOMAS, R. M1., aiid LE COMI'TE, 1'. M1. (1938), Wright & Sons, Bristol). The Biology of Arteriosclerosis (Chas. C. Thommias, Springfield).

A NEW TEST FOR PREGNANCY By R. E. ELKAN, L.R.C.P. & S. History more like those required for keeping fish for, likeProtected by copyright. It is now fifteen years since Hogben published a them, these toads spend all their life in the water. little note in the Proceedings of the Royal Society This habit makes xenopus even more suitable as of South Africa on the relation of the Pituitary a laboratory animal because they can be kept, Gland to Ovulation and Skin Secretion in Xenopus fairly crowded, in simply constructed tanks and laevis. Since that time, this toad, so far only if they are only well fed and supplied with plenty known to a few zoologists, has been introduced, of fresh water they survive, even under laboratory first hesitantly and then with enthusiasm, into conditions, very well. Indeed, if some of them the physiological laboratories of many countries. did not occasionally die through being used for Its natural habits and its behaviour in the tests or from infestation with fluke larvae their laboratory-so different from that of other amphi- life in captivity might be I5-20 years. by many authors; it has Many observations have been published on the bia-have been studied breeding of xenopus in captivity. Aquarists, tired been bred in large numbers, in London, New York, http://pmj.bmj.com/ Basle, Berlin, and elsewhere, and even during the of this "uninspiring" toad that would not breed war there has been such a demand for these toads in their aquaria, exiled it to a disused tank in the in Cape Town that it is often impossible to obtain back garden, and after a few weeks found there supplies. It is fortunate that lately the South hundreds of tadpoles. Imitation rain and change African Department for Inland Fisheries has taken of the pH have sometimes been successful, some- in supply of xenopus. In their times not, and it must be said that without the an interest the use of the syringe xenopus is a most capricious country of origin there should be no difficulty of hormonal breeding them in large numbers, and experience breeder in captivity. Under artificial on September 26, 2021 by guest. are taken, stimulation, however, it is not difficult to obtain has shown that, if proper precautions fertilised eggs and the tadpoles grow up into small the transport to London or elsewhere presents no frogs during the summer season (Fig. 6). During that great difficulties either. time they can be fed with infusoria, liver emulsion, dried egg emulsion or blood. In a well stocked aquarium, and if not too numerous, they need not Biology be fed at all and can be seen to feed partly after the Xenopus (Fig. i) is classified as a toad of the genus manner of whales, straining the water through their aglossa by the zoologists, but it neither looks even gill slits, partly nibbling at the infusorial growth remotely like the toads we know in Europe, nor which covers the water plants. Their gills are just are his habits similar to theirs. From the visible, for a day or two after hatching. After that laboratory worker's point of view the arrange- they undergo retrogression and the tadpole has to ments that must be made to keep xenopus are come to the surface every few minutes for a breath