Ediciones > Año 1948 > Artículo No. 1 2 3 4

Studies On The Reticulum In The Different Types Of Leprosy
Martin Vegas; Jacinto Convit; José Espin
International Journal of Leprosy. 15: 449, 1948
REVISTA: Publicaciones - Dr. Jacinto Convit

NUMERO: Año 1948

TITULO: Studies On The Reticulum In The Different Types Of Leprosy

AUTORES: Martin Vegas; Jacinto Convit; José Espin



STUDIES ON THE RETICULUM IN THE DIFFERENT TYPES OF LEPROSY 1 MAirrlN VEGAS, JACINTO CoNVI1&#39;1 AND JOSB ESPIN Car(IC43, V mtezuelo INTRODUCTION The modifications or alterations of the reticular structures in the pathological pr:ocesses of leprosy have not yet awakened t.he intereat of investigators of that disease, and their role in those processes is still unknown. Their importance ís grea.t, however, because these elements are intimately related to the pathological physiology of the reticulo-endothelial system. The literature on· the significance of the behavior of the reticular tissue in many other fields of pathology has been studied exten.sively, especially from the histological point of view. Numerous papers have been published regarding the nature of its fibers, its origin and its relationship to the cellular elements of the ·connective tissues. However, this abundance of publications does not mean that the problems conc.erne-d are sol ved; on the contrary, opinions expressed by different authors are very much in conflict. Despite the existing uncertainties regarding many features of this matter, there are severa) facts that have been definitely established. The fibers which constitute this tissue can be differentiated from the collagen fibers, because they are profusely anastomosed. The substance from which they are formed, although very closely related to collagen, is not identical with it. The reticulum fibers do not swell under the action of acetic acid, and they are resistant to potassinm hydroxide (10% solution). They are not stained by the aeid dyes employed for the demonstration of collagen, and they take up colloidal silver-applied by the methods . of Bielchowsky, Achucarro, and Rio Hortega and thelr modifications more intensely; they change to dar k brown or black, while the collagen becomes yellowish or a pale yellow. Authors like Mallory and Parker do not believe that reticulum is fundamentally different from collagen, because there is no interruption of continuity between them. Foot thinks that the 1 Preunted at the Fifth International Leproey Con~. held in Ravana, April S~ll, 1948. The baaic EngHah translation from the original Spanish was supplied by the autbora. • &#39; 443 .444 l nterruúiona,l J ourna.J of Lepro811 1948 special property of fixing silver shown by reticulum is due to a substance with which its fibers are impregnated, and which can be dissolved by sodium hydroxide. Dublin con.siders reticulum as a precursor of collagen and very similar to it, though dilfering in some of its physico-chemical characteristies. Siegfried believes that the substance which fonns reticulum has specific characters, and calls it reticulin. MaU is of the same opinion, although at first he thought the substance was related to elastin. Laguesse considers reticulum as a variety of collagen containing elastin. Del Rio-Hortega distinguiShes two varieties of these fibers: (a.) one which forms the network of the hemopoietic organs and the thymus, which according to hls opinion would be the reticulin, and ( b) one found in other organs and glands, which would be precollagen. We ourselves use both terms--reticulum and precollagen- indiscriminately, since a distinction has not yet been sufficiently established. Another of the matters of discuasion is the relationship between these fibcrs and the cellular elements-the connectivetissue and reticular ceJls. For sorne authors the fiber8 are independent of the ceH protoplasm, and are fonned by different meehanisms in the intercellular spaces, while others believe they are of intracellular origin. According to Nageotte and Guyon, the reticulum of nerve and muscle contains fibrobla.sts; but in the adipose tissue those cells are found only in the col1agenous connective- tissue zones about the fat lobes, so the question remains what cells are responsible for the íormation of reticulum. Apparently there is no doubt of the intraprotoplasmic situation of tbese fibers when the stromas of the splenic, ton.sillar and lymphoid tissues are considered. The fibers of these stromas are in intímate relationship with the endothelial cells of the • vessels, constituting wbat was formerly known as &#39;the reticuloadenoid tissue. Recent data h.ave proved that this is true, at least under sorne eircumstances. \{any authors accept the intracellular origin of the coUagen fibers. Tello speaks of ,.endocellular inofibers" in describing his tissue cultures, and Bloom and Sanderstróom have the aame belier. So has Costero as a result of his study of the placenta; both he and Del Rio-Hortega, who differentiated sarcomas, found argyrophil precollagen fibers in the cytoplasm of fibroblasts. Taking for granted that the reticulum derives from the cellular elements, directly or indirectly, only the endocellular theory is capable of explaining satisfactorily the activities and funetions which this substance performs in nonnal and pathological processes ( inflammatory, productiva, scarring, etc.), and 16,4 V ega,s et al Reticulu.m in Lepro8&#39;11 445 also its permanence and growth in determined zones in which other fibers degenerate or die. It must be remembered, however, that the reticuJum fibers are absent in tuberculous ca.seation, where the elastic fibers are not destroyed, a fact which is related to the absence of blood vessels in the tuberde (Costero) . One of the most interesting points about the reticulum is its capacity of development, not only in the pbysiological processes (regeneration of the uterine mucous membrane and of the formation oí the corpora Jutea), but also in certain pathologieaJ proe~. lts development increases, ac-cording to Costero, after a necrotic process. Foot says, "this growth is stimulated by the tubercle,&#39;&#39; an assertion which, in our opinion, is an error of interpretation because it is known that reticulum is the constituent element which appears with regular characteristica and simultaneously with the eclls which form the tubercle. In the scarring processes apparently, reticulum perforrns a very important function, as has been pointed out by Foot with respect to regression of the tubercles in chronic pulmonary tuberculosis, and by Espín in the regressive phenome non o! the tuberculoid nodule produced by the eggs of Schi8tos0&#39;7TUL manscmi. lt seems that. not only the fibroblasts and reticulo-endothelial cells are capable of producing reticulin, but that the endothelium of the blood capillaries also poss~~s this capacity (Corner). That is why the blood capillaries have these fibers as constant elements in their structure. We do not find them in the lymph. atic capillaries. The papera which deal with the intervention of reticulum in the pathology of the skin are few. Bizzocero, using Bielchowaky&#39;s procedure, studied the behavior of reticulum in syphilis, tuberculosis and leprosy, the conclusions of his short note being as follows: The chronic inflammatory process of syphilitic nature provokes neoformations of reticulum; in the leproma the reticulum fibers are arranged in such a way that they give lod.gment to the specifie vacuolate (Virchow) cells; in the tubercle the fibers are profusely branched in the Jymphocytie zon.e but are very scaree in the central, epithelioid zone. Way studied the reticular changes in the dermis in a large series of dennatologi- · cal affections but makes no reference to the behavior of the reticulum in leprosy, tuberculosis, or Boeck&#39;s sarcoid. Dublin, dealing with the reticulum in general, refers to the reticular formations in different specific granulomas, among them tuberculosis of the skin, and arrives at conclusions similar to those of Bizzocero. In syphilis, like Costero, he also tound abundant neoformations of reticulum mainly in the gumma; in leprosy, he 446 lnternational Journal of Lqrosy 1948 states, the histiocyte deposits r-eticulum freely in different ways, according to whether the leaions are tuberculoid or lepromatous. METHODS The material studied by u.s consista of biopsy specimens which are sent as a matter of routine from the dispensaries and leprosaria to the Laboratory of the Central Leprosy Service in Caracas. All the material had been fixed in 10 per cent fonnalin. Most of it was imbedded in paraffin and impregnated by Wilder&#39;s silver method, but sorne was cut by the freezing technique and impregnated by Del Rio-Hortega&#39;s method. The former method is the more useful one for routine work, but the results obtained with it do not show the fine details revealed by the latter method-which, however, has· the disadvantage of being the more laborious and neee.ssitating the use of frozen sections. A total of 40 specimens has been studied, including both the lepromatous and neural tjrpes, the latter in its two forJruL tuberculoid and simple macular. This number of specimens is small, but they were seleeted with much care from a collection of one thousand, choosing only cases which were typical from the clinical and anatomopathological points of view. RESULTS A common and fundamental characteristic of alt our material studied is that the reticular formations found were located exclusively in the inflammatory zones. That is to say, we have not observed any alterations in the reticulum outside of the granulomas or the zones of inflammation. . Simple macular patche.s.-In these lesiona the inflammatory infiltrations are found in the proximity of capillaries and small blood vessels as well as around the nerves and pilo-sebaceous follicles. The reticular formations observed are very slight, and are represented by very thin threads placed radially, starting from the preexistent reticulum belonging to the structures mentioned. These fibers are very fine and almost straight; rarely are they branched. lt is only occasionally that· they anastomose with each other directly or by secondary branchea, and they do not form real nets. Tbe fibers grow thinner as they move away from their supposed centers of formation, until their distal extremitiea finally make contact with the dermal collagenous bundles. (Fig. 1). Lepromat()tU t&#39;JfPe le.tions.-Here we must separate the small, incipient lesions from the bighly developed lepromatous 16,4 V ega8 et al: Reticulunt in Lepr08tJ 447 granulomas which involve extensive portions of th.e dermis. In the former case, the normal structures of the aldn are undamaged, and only in small zones do we observe the typical lepromatous condition, which generally centers around a small blood vessel or capillary. The reticular threads can be distinguished easily, since thcy appear clearly and pr·edsely and forrn a net which joins the collagen with the granuloma. The fibers of this network are of different thlcknesses, but in general thin ones predominate. There is much anastomosis among them, by the intervention of other smalle. r and thjnner fibers which form the nets whose meshes adapt themselves to the sizes of the cells forming the granulomas. This type of formation reminds us of the lymphatic nodules scattered about in the intestines, though they differ because their fibers are mor~ delicate and their course more sinuous (Fig. 2). When the lepromat.ous granulomas are well developed, we observe that the normal cellular elements o! tbe dermis are missing, and also the collagen bundles. The latter element r~ mains as a thin band in the deeper level and also as thin walls or partitions distributed in the mass of the leproma, limiting the nodules. This remnant of the preexistent colJagen is very dense. and its appearance indicates that it is being submitted to much pressure resulting from the growth of the elements of the&#39; granulomas. The reticular nets are formed by profusely anastomosed branehes, the meshes be\ng arranged by means of the cells in a manner similar to that observed in the ineipient lesiona. The fibers are generally thieker, however, and-though we cannot say that this is an established rule the thicker ones tend to arrange themselves perpendieularly to the epidennis. Among these nets there can be distinguished a finer and less branched reticolum which c-ontributes to the formation of tubes belonging to the newJy formed blood ca pillarles; and they also arrange themselves as do the lhicker fibers (Fig. 3). Tttberculoicl tVPe luions.-Tbe development of the reticulum in the tuberculoid granuloma is more irregular than in the Jepromatoos lesion. This irregularity pertains not only to the thick· ness of the fibers, but also to t.he number of the different regions of the granuloma, and in relation to its cellular elements. The threads m.ay be very broad, and occasionally they appear mjcroscopically as if they were real protoplasmatic banda. Such fibers may coexist with other very fine ones, and betwee.n them we observe a wide dive.rsity of thieknes.ses. The ramification_s and ana.stomoses of these threads are more abundant in the periphery of the granuloma (where the thicker ones are to be found) than 448 lnternational Journal of Lepro~y 1948 in the inner zones occupied by the giant and epithelioid cells. In • fact, the fibers are more sca.ree in the latter location, and they present fewer branches and grow thinner. In general, we have observed that they do not make contad with the giant oells (Figa. 4 and 6). When the inflammatory pr()(ess affe<:ts the nerve, the reticular fibers are arranged around it, forming very regular conoentric circles, and they settle in the region of the neuritis (Fig. 6). In theae cases the fibers are circular, with very little if any branching, and they are not placed in a radial position. The formation.s which a!fect the hair follicles and aebaceous gland.s are very irregular, consisting of long and thin fibers, with slight branching. ln the region of the coil glands the newly formed threads are very thin, at least when the inflamrn.atory process is beginning (Fig. 7). When it is more developed the aspect is similar to the typical tuberculoid granuloma. In general, the reticular neoformations in the leprómatous and tuberculoid granulomas tend to form a tridimensional ne~ work with meshes of different sizes, though always small, which give lodgment to the celJ.s which form the granulomas (Fig. 8). Occasionally, mainly in the tuberculoid granulomas, we have observed the phenomenon of transformation to c.ollagen, more or lesa accentuated. We did not observe the intervention of the proper reticulum oí the erector pili muscle in any of the. described lesion forma. The aubbasal reticular layer does not seem to interfere with these format ions. CO!U!ENT From our observations, and bearing in mind the general knowledge of the reticulum and its behavior in other specific granulomas auch as tuberculosis and schistosomiasi.s, we think that the reticular neoformation which accompanies the different forms of leprosy lesiona improves the organic defenses against the activity of the bacillus. These detenses are related to two fundamental processes : fil&#39;8t, the providing of a collagen net and its location; and second, the ultima te chaJlg&#39;e to scar tissue. At the same time it is probable that the reticular neoformation cooperatea in the nutritive activities. The movement of the wandering cells (histiocytes) toward the affeeted zones playa an important role in the defense. Costero demonstrated that the macrophage eells, when passing over preeollagen fibers, ha ve about two hundred and thlrty times the mobility of which they are capable in a nontissue coagulum. Moreover, due to the slight expansion capacity of the oollagen, 16,4 VeglU et al: Retictdwm. in Leprosy 449 it is natural that other elements are needed which by thei r chara.cteristics facilitate the building of defensive granulomas such as those observed in leprosy. The reticulin threads are an ideal material for this purpose, becAuse of its self-growth and great flexibility. As an earlier element in Ole formation or collagen, it facilitates retraction and scarring in the healing procesa of the lesions. . It would be of great interest to be able to prove the same thing of the regressive phenornenon suffered by the leprosy lesiona with the treatments used toda y ( chaulmoogra oil and sul!one drugs). Here it has been observed, in sorne cases which had a favorable oourse, that collagen f orrnation· and fibrosis are much accentuated in&#39; the interior of the lepromatoas gran ulomas (Convit and associates). SUMMARY AND CONCLUStONS We have studied retieulum forrnation in the two types of leprosy, lepromatous and neura1. Reticulum, according to our observations, is a constant element in the · inflammatory reaction zones of the simple ma.cular lesion, and in the lepromatous and tuberculoid granulomas. These reticulum forma.tions, very simple in the infiltrated zones of the simple macular, grow complex. in the lepromat.ous type, and in the tuberculoid variety adopt the characteristic forms described by other authors in tuberculoid granuloma.s of other origins. The normal arrangement of the reticulum is a tridimensional network whose meshes give lodging to the cells which fonn the granuloma.. Apparently these formations play an active role in the defensive procesa of the organism against the leprosy ba.cillus. 460 lnternational Journal of Leprosy DESCRIPTION OF PLATES · PLAn: U 1948 Fto. l. Simple macular lesion. Blood eapillary, with elight. reticular neoformation. Notioe · the continuity wit.h the retíe:ulum proper of the eapillary. (Wilder&#39;a method.) FIO-. 2. Small lepromatous nodule. This shows a eapiUary and its re.t.ieulum flbers anaatomosed with the collagen. (Dol Rio·Rortega&#39;a method.) Fra. S. Lépromatoua nodule. Almoat. complete absenee of tbe normal eollagen element; abundant reticular fibers, gN!atly ana.st.omosed, forming a cloud net. (Wildera mdhod.) F1a. • · TubercuJoid granuloma, nodular formationa. Collagen preaent; abundant anaatomosis of reticular fibers. (Wilder&#39;a method.) AL) Pt.ATf.! 25 Fu;. 1>. Tuberculoid granuloma, Giant cell and reticulum in the central U>ne. Notiee that the reticular fiben; are well aeparated from fhe giant eell. (Wilder&#39;a method.) FJG. 6. Tubereuloid granuloma, transverso ~ction of a nerve. The retieulum fiber3 are coneentric, situated exelusively in thc infiltrated U>ne. (Wilder&#39;a met.hod.) Ftc. 7. Tuberculoid leprosy. Very slight reticular !onnation in the c.oil-gland zone, more ac:centuated in the apieal zone. (Wilder&#39;s method.) F1c. 8. L.epromat.olts granuloma. Det.ails a-howing three types of thiclcneuea of the í ibers and their relations with the co!lagen. (Del Rio· Horttga method.) \&#39; IC&#39;(; .\>( • lCT A l.) J.;ct•wQ v , \ &#39;Oc.. 16. Xu • .a Pu:re 25
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