Bronchopulmonary anastomoses sickle-cell anaemia · Bronchopulmonary anastomoses in sickle-cell anaemia being surrounded by thick septa of fibrous tissue (Fig. 2). A few elastic pulmonary

Thorax (1969), 24, 232.

Bronchopulmonary anastomoses in sickle-cell anaemiaDONALD HEATH AND IAN McKIM THOMPSON

From the Departments of Pathology, University of Liverpool, and the East Birmingham Hospital

Histological details are given of bronchopulmonary anastomoses in a patient who died suddenlyand was known to have sickle-cell anaemia.

Histological studies of a recent case of sickle-cellanaemia provided an opportunity to elucidate themicroanatomy of bronchopulrmonary anasto-moses. These are often referred to in papers deal-ing with disturbance of the pulmonary circulation,but their detailed structure has rarely beendescribed.

CASE REPORT

The patient was a negro man aged 28 years whocollapsed suddenly and died in the street followinga vague history of pain in the chest. In view of thesudden unexpected nature of the death H.M. Coronerwas informed and ordered a necropsy to be per-formed. Subsequent investigations revealed that theman had experienced similar pain in the abdomenseven years before. It further transpired that he hadpreviously suffered a spontaneous peripheral detach-ment of the left retina. Operation for this was carriedout successfully. The diagnosis of sickle-cell anaemiahad been queried and was confirmed by electro-phoresis of haemolysed red cells on a cellulose acetatestrip. The 'S' and 'C' bands were plainly visible andtypical. Subsequently he developed further ophthalmo-logical complications in the form of retinal detach-ments and cataract which resulted in virtual blindness.

NECROPSY FINDINGS The salient features were thaton cut section the lungs presented a remarkableappearance of widespread and severe thrombosisof the pulmonary arteries. The thrombus appearedas solid dark red cords which protruded frommost of the pulmonary arteries, ranging in sizefrom lobar vessels down to small elastic pul-monary arteries.The heart, devoid of fat, weighed 275 g. The

right ventricle weighed 65 g. (upper limit of nor-mal), the left ventricle 175 g. (normal), and theatria 35 g. The ratio of left to right ventricularweight was 2-6, which is normal and not indicativeof isolated right ventricular hypertrophy. Theheart valves were normal in structure and circum-ference. There was no coronary thrombosis. Thespleen (50 g.) was small, shrunken, and fibrotic.

It was brownish in colour due to deposition ofhaemosiderin. The other organs were congestedbut showed no structural abnormality. Death wasconsidered to be due to widespread pulmonarythrombosis associated with sickle-cell anaemia.

Pulmonary vascular pathology There was wide-spread occlusion of the elastic pulmonary arteries(>1,000 pt in external diameter) by recent, organ-izing, and organized thrombi (Fig 1). In many ofthese vessels large clumps of thrombus had under-g.one organization with the formation of excentricnodules of fibrous and fibroelastic tissue closelyadherent to the intima (Fig. 1). In other arteriesthere was extensive recanalization with the forma-tion of colander-like lesions, large patent channels

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FIG. 1. Transverse section of an elastic pulmonary arteryshowing clumps of recent thrombus with evidence oforganization and incorporation into a thick fibrous liningto the vessel. Other pulmonary arteries were totallyoccluded by this process. (Elastic! Van Gieson, x 25.)

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Bronchopulmonary anastomoses in sickle-cell anaemia

being surrounded by thick septa of fibrous tissue(Fig. 2). A few elastic pulmonary arteries con-tained bands and webs, thinner strands of fibro-elastic tissue being stretched across the vascularlumen; these webs clearly represented a moreadvanced stage of organization of the colander-like lesions.

FIG. 2. Transverse section ofa muscular pulmonary arteryshowing a classical 'colander lesion' due to recanalizationof organized thrombus. The underlying media shows atro-phic change secondary to the thrombus occluding the vessel.(Elastic/ Van Gieson, x 65.)

Wi.thin the organized thrombus were numerousblood capillaries (Fig. 3) which predominated inthe zone immediately subjacent to t;he internalelastic lamina. Some of these thin-walled vesselswere much larger, and a few of them had a dis-tinct muscular media sandwiched lbetween 'twoelastic laminae. In many areas the media under-lying organized thrombus had undergone atrophywith loss of musculoelastic tissue so that themedial thickness was reduced from something ofthe order of 250 u down to a thin elastic coatabout 30 pt thick. In these areas there was dis-ruption of the elastic fibrils of the media, andmany of them appeared frayed (Fig. 3). Smallcapillary vessels coursed through these areas ofdisrupted media (Fig. 4) and communicated withbranches of prominent bronchial arteries whichsurrounded the elastic pulmonary arteries formingtheir vasa vasorum. These were recognized bytheir thick intimal coat of longitudinal muscle, a

media taking up the Van Gieson stain compara-tively faintly, a distinct t-hick internal elasticla,mina, and a virtually absent external elasticlamina (Fig. 5). These bronchopulmonary anasto-moses are described in detail below.The 'muscular pulmonary arteries' (between

100 u and 1,000 IL in external diameter) were thin-walled and showed none of the structural featuresassociated with pulmonary hypertension. Some ofthem contained organizing thrombus. The pul-monary arterioles had a coat consisting of a singleelastic lamina, and there was no evidence ofmuscularization of this wall such as occurs inpulmonary hypertension. The pulmonary capillarybed was prominent due to the distension of capil-laries by tactoids and microthrombi. The pul-monary veins showed minimal intimal fibrosisconsistent with normal age change.

Bronchopulmonary anastomoses The microscopicstructure of a typical acquired bronchopulmonaryanastomosis (A) is shown in Figures 5 to 8. In

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FIG. 3. Part ofa transverse section ofan elastic pulmonaryartery. To the right the lumen is occluded by organizedthrombus which contains a recanalization channel. Themedia shows early fragmentation of its elastic laminae.(Elasticl Van Gieson, x 115.)

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Donald Heath and Jan McKim Thompson

monary artery and the exit of the dilated recanal-ization channel at higher magnification. Theragged edges of this exit vessel with fragmentation

AV $,, a, .... {.d .sts sj '.......anddisruption of elastic laminae shows this ves-sel to have been acquired as a result of a diseaseprocess and contrasts sharply with the well-

qh.;i,ordered and neat arrangement of the media andits elastic laminae at the normal origin of amuscular pulmonary artery from a paren,t elasticpulmonary artery. This connecting vessel (Fig. 7)consists of muscle fibres but is virtually devoidof elastic tissue. It has the structure of neither a;pulmonary nror a bronchial artery. It leads into ablood vessel with the characteristic histologicalstructure of a systemic artery with a well-defined

VicYtg 9 v lista a 3$ F media of circular muscle and an internal elasticlamina, although the external elastic lamina is

t88<8;5;b_IS'J*^': t{< 5 =1S, is >S. virtually absent (Fig. 8). This vessel is a bronchialartery and completes the bronchopulmonary ana-

1iti\tv@*K-9 o **XS S 11 z Nff ,.e, <. stomosis.Another such anastomosis (B) is shown in

A, < .: t ;!;.<;;;Figures9 to 1. In Fig. 9 the organized thrombusN,s ;; t t # @1 ^ ^ SaF which occludes the elastic pulmonary artery is

shown to the upper right. Small recanalizationi;*3ij*x.Sq9X ; - channels are visible in this mass. One of these

FIG.4 Part ofa transverse section ofan elasticpulmonaryartery. To the right the lumen is occluded by organized *>thrombus which contains recanalization channels. Theunderlying media shows considerable fragmentation of , .elastic fibrils which leave ragged edges. There is also muchseparation of elastic fibrils. Between these are situatedthin-walled vascular channels which communicate with boththe recanalization channels in the organized thrombus andwith thin-walled vessels in the adventitia. (Elasticl VanGieson, x115.)

Fig. 5 the entire anastomosis is shown; fortuitouslyit has been sectioned longitudinally throughout its .. $entirety. The disrupted media of an elastic pul- ¢ EEmonary artery shows the fragmentation and sep- 4aration of elastic laminae previously referred to. .It runs obliquely downwards from the upper rightto the lower left of the picture. Above and to itsleft the lumen of the elastic pulmonary artery isoccluded by organized thrombus which, however, fcontains small recanalization channels. There is Wa break in the media with ragged edges. One of -A'*,,the recanalization channels has dilated and has -broken through the fragmented media to pass i S.i jvertically downwards to effect communication .with a bronchial artery running obliquely upwardsand parallel to the elastic pulmonary artery. FIG. 5. The entire bronchopulmonary anastomosis (A)Figure 6 shows the break in the media of the pul- described in the text. (Elastic/ Van Gieson, x 76.)

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FIG. 6. The first part of the exit channel which appears tohave broken through the ragged media. (Elasticl VanGieson, x 150.)

FIG. 7. The secondpart ofthe exit channel which connectswith the blood vessel in the adventitia of the elastic pul-monary artery. (Elasticl Van Gieson, x 150.)

FIG. 8. The bronchial artery completing the broncho-pulmonary anastomosis. (Elasticl Van Gieson, x 150.)

FIG. 6

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channels passes down vertically to break throughthe media of the pulmonary artery which formsan arc traversing the upper right portion of thefigure. The elastic fibrils of the media show exten-sive fragmentation and separation, and the edgesare ragged in striking contrast to the orderlyarrangement of the emergence of a normal branchof an elastic pulmonary artery (Fig. 10). This thin-walled vascular channel communicates with anartery in the adventtitia of the elastic pulmonaryartery (Fig. 11). In this case the structure of theartery completing the bronchopulmonary anasto-mosis is distorted, considerable fibrous changeaffec,ting both its media and intima (Fig. 11). How-ever, its situation leads one to conclude that, asin the first anastomosis, it is certainly bronchial innature.

DISCUSSION

The cause of pulmonary thrombosis in sickle-cellanaemia, which particularly affected the elasticarteries of the lung in this patient, is a geneticallydetermined defect in the chemical constitution ofthe haemoglobin. Human haemoglobin has twopairs of chains, designated a- and f-. During oxy-genation the spatial configuration of these chainsalters such that the ,B-chains move together about7A. Sickle-cell haemoglobin differs from normalhaemoglobin by the substitution of valine forglutamic acid at the sixth position in the fl-chain.This substitution alters the configuration of theterminal residues of the fl-chain such that on

deoxygenation it interacts at a complementary siteon an adjacent a-chain. This interaction results inmolecular stacking with the production of tactoidsand a rigid deformity of erythrocytes.The widespread thrombosis in the elastic pul-

monary arteries must impede pulmonary flow andelevate pulmonary vascular resistance. This in turnleads to right ventricular hypertrophy and affordsadequate explanation of the development of corpulmonale in sickle-cell anaemia. The pulmonaryarteries distal to the organized thrombi are clearlynot subjected to an elevated pressure and, as hasbeen noted, remain thin-walled.

This case is of interest in demonstrating themode of development of bronchopuimonary ana-stomoses in sickle-cell anaemia, which is mostlikely the same in any disease associated withchronic pulmonary thrombosis. Such anastomosesare so frequently referred to in papers dealingwith the pathojphysiology of the pulmonary cir-culation that it is salutary to recognize howrarely the morphology of these vascular con-

nexions has been described in detail. Wintrobe(1961), for example, notes that unsaturation ofsystemic arterial blood is comparatively frequentin sickle-cell anaemia and suggests that this is dueprincipally to intrapulmonary shunting of blood.He does not, however, describe the form or modeof development of such shunts.Bronchopulmonary anastomses occur in normal

lungs where they are found in the walls of bronchiand in the pleura supplied by bronchial arteries(Wagenvoort, Heath, and Edwards, 1964). Inadults they are rare and appear to be branchesof bronchial arteries since their structure is muchmore like t;hat of a bronchial than a pulmonaryartery. In this respect they show longitudinalmuscle in the intima. These anastomotic vesselsare usually narrow and tortuous, although widestraight forms may be found. They run a shortcourse of up to 300 jI in length and probably havelittle functional significance in the lung of theadult free of cardiopulmonary disease. Broncho-pulmonary anastomoses are common in the foetusand infant where they form wide straight vessels.In that part of their course where they run to joinradicles of the pulmonary arterial tree, they havethe tyipical structure of a pulmonary artery. Allnormal bronchopulmonary anastomoses thus con-sist of well-formed arteries with an orderlyarrangement of muscle coat and elastic laminae.

In striking contrast to these is the acquiredform of bronchopulmonary anastomosis whichhas the ragged appearance described in detailabove. Anastomotic vessels of virtually identicalstructure to those we report here have been de-scribed by Cudkowicz and Armstrong (1953) incases of emphysema. They found that, in severeexamples of this disease, hypertrophied bronchialarteries sometimes communicated with fibrosedpulmonary arteries lying in apposition to damagedbronchi. The vascular connexions were rarelylarger than 100 ju in diameter, and seemed to bebranches of bronchial vasa vasorum w,hich pene-trated the media of the large elastic pulmonaryarteries to recanalize organized thrombus occlud-ing the lumen of the pulmonary artery. Broncho-pulmonary anastomoses of identical type may befound in those cases of bronchiectasis associatedwith thrombosis of elastic pulmonary arteries(Wagenvoort et al., 1964).These are different in structure from the com-

mon type of bronchopulmonary anastomosiswhich has been described in bronchiectasis by Lie-bow, Hales, and Lindskog (1949). These are foundadjacent to bronchiectatic sacs alongside bronchiof the fourth order of branching. The bronchial

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arteries spiral before communicating with thepulmonary arterial tree, the coils being tight, wide,and numerous. The bronchial artery is of thesame size or slightly smaller than the pulmonaryartery with which it connects. They are of theacquired variety and appear to develop from capil-laries of granulation tissue which is derived fromboth bronchial and pulmonary circulations.The function of such bronchopulmonary ana-

stomoses and the direction of flow of bloodthrough them are uncertain. They may provide asecond systemic source of blood to enter the peri-pheral pulmonary arterial tree deprived of a nor-mal flow of blood by the widespread thrombosis.Alternatively, it is possible that the flow of bloodtakes place in the opposite direction, that is fromelastic pulmonary arteries to bronchial arteries,providing a decompression valve from the proxi-mal portions of the pulmonary arterial tree sub-jected to hypertension.

Here we report only the bronchopulmonaryanastomoses and the pulmonary thromboses, butit is worth mentioning that retinal complicationsand pulmonary thromboses are not uncommon inhaemoglobin sickle-cell disease.

We wish to thank Mr. George Billington, H.M.Coroner to the City of Birmingham, for permission toreport this case.

REFERENCES

Cudkowicz, L., and Armstrong, J. B. (1953). The bronchial arteries inpulmonary emphysema. Thorax, 8,46.

Liebow, A. A., Hales, M. R., and Lindskog, G. E. (1949). Enlarge-ment of the bronchial arteries and their anastomoses with thepulmonary arteries in bronchiectasis. Amer. J. Path., 25, 211.

Wagenvoort, C. A., Heath, D., and Edwards, J. E. (1964). ThePathology of the Pulmonary Vasculature. Charles C. Thomas,Springfield, Illinois.

Wintrobe, M. M. (1961). Clinical Hematology, 5th ed., p. 673.Lea and Febiger, Philadelphia.

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Bronchopulmonary anastomoses sickle-cell anaemia · Bronchopulmonary anastomoses in sickle-cell anaemia being surrounded by thick septa of fibrous tissue (Fig. 2). A few elastic pulmonary