The vascular architecture of the small intestinal mucosa of the monkey (Macaca mulatta).код для вставкиСкачать
The Vascular Architecture of the Small Intestinal Mucosa of the Monkey (Mcrcaccr mulatta) DAVID G . REYNOLDS, .TACK BRIM AND THOMAS W. SHEEHY Drpartment of Gastroenterology, Division of Medicine, Walter Rred Army Institute of Research, Walter Reed Army Medical Crnter, Washington, D . C., and Department of Medicine, Walter Reed Generul Hospital, Walter Keed Army Medical Center, Washington, D. C. ABSTRACT Silicone rubber microvascular injection compounds have been used to describe the mucosal vascular architecture of thc monkey’s small intestine. The mucosal vascular patterns of this animal differ from the classical description. Instead of the villus blood supply being delivered via a central villus arteriole, the arterioles ramify to the undersurface o l the mucosa where they terminate i n the capillary plexus surrounding the crypts of Lieberkuhn. The villus capillary net is derived directly from the cryptic capillary plexus and is drained by a single, central villus vein. There is a secondary venous return system that directly drains the cryptic plexus. These secondary venous channels might represent a mechanism that regulates the proportional distribution of blood iii the cryptic and villus capillary beds. This report is intended to describe the vascular patterns only as they occur in the monkey. Observations of rat and rabbit mucosa prepared by the same technique reveal arterial and venous channels extending the length of the villi. These animals, therefore, more closely resemble the classical description. BIoom and Fawcett’s (’62) description of the vascular architecture of the intestinal mucosa which we shall call the classical description contains a dual arterial supply. One set of arterioles supplies the capillary network surrounding the crypts of Lieberkuhn while the second passes directly to the villi. These latter arterioles pass axially through the bases of the villi to the apices where they bifurcate, with one branch supplying the dense capilIary network underlying the surface epithelium, and the other anastomosing with a vein. Venous return is accomplished through a pair of marginal villus veins. This concept of villus vasculature stems from Mall‘s foulztak configuration (1887) and incorporates Spanner’s (’31) modification of the apical arteriovenous anastomosis. There are, however, reports of villus vascular architecture that are inconsistent with the classical description. Jacobson and Noer (’52) studied the villus vasculature in rabbit, dog, opossum, and man concluding that : ( 1 ) The villus capillary net is derived from both the villus artery and submucosal plexus; ( 2 ) ‘The axial vessel i s venous in nature;” and ( 3 ) “Arterial supply and venous drainage exist throughout the villus from tip to base.” AXAT. REC., 159: 211-218. The vascular pattern of rat villi as recently reported by Mohiuddin (’66) is compatible with the findings of Jacobson and Koer. Sobin et al. (’62, ’63) introduced and described a silicone rubber injection medium (RTV-201) ’ that is ideally suited for microvascular studies in that it thoroughly fills all vessels, including the smallest capillary channels. The use of these materials in microvascular studies has been validated and their physical properties described (Sobin, ’65). In addition, this material has been used successfully by other workers in microvascular studies, Demis and Brim (’65) and IIase (’66). This material was used in the present study of elucidate the microcirculatory pattern of the intwtinal mucosa of the monkey. With this technique, the vascular structure of the jejunal and ileal mucosa of Macaca mulatta was found to differ markedly from that of the classical description. METHODS The specimens described in this report were taken from seven animals in which the entire gastrointestinal tract had been . .~ 1 Silicone Products Department, General Electric Company, Waterford, New York. 211 212 DAVID G. REYNOLDS, JACK BRIM AND THOMAS W. SHEEHY prepared. The principles of laboratory animal care as promulgated by the National Society for Medical Research were observed. The animals were anesthetized with nembutal, and heparinized. In order to achieve complete filling of all vascular channels of the gastrointestinal tract, the visceral vascular bed was perfused thoroughly with saline prior to infusing the silicone rubber. Saline perfusion and rubber infusion were carried out through a polyethylene cannula placed in the thoracic aorta and advanced distally until its tip extended just below the diaphragm. The right atrium was opened to serve as a drain vent. Following saline perfusion, the silicone rubber injection mass was infused by hand with a syringe. The infusion was Fig. 1 continued until, at completion, the rubber flowed freely from the atrial vent and all organs were thoroughly filled as evidenced by their uniform coloration. The arterial cannula and atrium were then clamped and the animal refrigerated overnight, during which time the rubber polymerized. Specimens were then removed and processed through a glycerin clearing procedure. Initially the tissues were placed in 50% glycerin and water for 24 hours. The glycerin concentration of the mixture was raised by increments of 10% every 24 hours untiI the solution was composed of 100% glycerin. At this stage, the tissue water had been replaced by glycerin sufficiently to reduce the optical density of the tissue appreciably and thus permit 3-dimensional microscopic examination of the Jejunal Villi as viewed from the lumenal surface. x 40. 213 VASCULAR ARCHITECTURE O F INTESTINAL MUCOSA vascular beds by using reflected, surface lighting. The tissues can be stored in 100% glycerin for extended periods. The recent introduction of silicone rubber compounds of different colors, (Microvascular Injection Compounds) ,2 has made it possible to prepare %color specimens and thus facilitate microscopic examination arid interpretation of the vascular patterns. In three animals, 2-color preparations were made by first completely filling the vascular bed with red RTV-201 material and then ovcrinjecting a small volume of yellow MV-122 into the arterial system. The abundant submucosal arteriovenous anastomoses permitted an extensive intermixing of the yellow rubber in the red. However, the yellow tag allowed us to identify readily the submucosal vessels and to make more precise microscopic identification. RESULTS The normal appearance of thc luminal surface of the monkey’s jejunal mucosa is shown in figure 1. The compIex and extensive nature of the capillary bed underlying the surface epithelium of the villi can readily be appreciated from this figure. The villus capillary bed forms a network of interconnected vessels in the upper half of the villus. The lower half of the bed is composed of vessels that essentially run parallel to each other and appear to be continuous with a plexus of capillary channels ramifying between the bases of the villi. The resulting subnillus plexus characteristically presents a honeycomb pattern and consists of capillary rings surrounding the luminal openings of the crypts of Lieberkuhn. The subvillus plexus extends through the cryptic layer of the mucosa as a rich plexus of capillaries surrounding the crypts themselves. The 2-color injection procedure was helpful in distinguishing between small mucosal and submucosal arterial and venous - ~ Canton Bio-Medical Products, Street, Canton, ~Massachnsetts. J See footnote 2. 3 1803 Washington Pig. 2 Jejunal submucosal vascular plexus viewed from the serosal aspect. The serosa and muscularis have been dissected away. A vein and parallel artery are easily identified. X 50. 214 DAVID G . REYNOLDS, JACK BRIM AND THOMAS W . SHEEHY channels (figs. 2, 3, 4 ) . In the specimen shown in figure 2 , the submucosal vascular plexus has been exposed by dissecting away the serosa and muscularis. Small arterial branches ( a ) bifurcate to form precapillary arteriolar twigs (arrows) that are distributed to the undersurface of the mucosa and run uninterruptedly into the capillary plexus of the mucosal cryptic layer. Venous channels are also in communication with the cryptic plexus but do not terminate at this level. Instead, the terminal branches penetrate the cryptic layer of the mucosa and a single, centrally located vein enters the base of each villus and extends to the apex (arrows in fig. 1). Details of the vascular architecture of several villi are shown in figure 3. In this photograph of a thick section of the intestinal wall, a branch of a large submucosal vein (v) can be seen entering the cryptic layer of the mucosa where it is continuous with venous branches running along the base of the villi. These latter branches receive the central veins (arrows) from the villi. It is also clear in this figure that the Fig. 3 villus capillary net is continuous with the cryptic plexus. The venous nature of the central villus vessels is also shown in figure 4. In this thin cross section, the submucosal vasculature is distorted due to &€ficulty in sectioning this thin-walled tissue. However, the uninterrupted course of the central villus vessel (arrow) to submucosal veins (v) remains obvious. Figure 5 illustrates a specimen in which the mucosa has been dissected free and folded back to expose the underlying venous drainage system. The venous channels are highly branched and characterized by venovenous anastomoses. In addition, there are vessels that extend directly from the under surface of the cryptic plexus to the larger venous channels (arrows). These vessels constitute a second avenue for venous drainage of the mucosa. The major features of the mucosal vascular architecture of the monkey are consolidated in schematic form in figure 6 . The arterial supply is distributed to the undersurface of the mucosa with the terminal arteriolar twigs running continu- Thick cross-section of jejunum, 2-3 mm. X 50. VASCULAR ARCHITECTURE O F I N T E S T I N A L M U C O S A 215 Fig. 4 Thin cross-section of jejunum, 100--150 p. The central vein of the indiyidud villus is continuous with the mucosal venous system. X 30. ously into the capillary plexus surrounding the crypts of Lieberkuhn. The capillary nets of the villi are derived directly from the cryptic plexus via a series of parallel capillary channels that extend from the lumenal surface of the cryptic plexus to approximately midlevel of the villi where they break into a mesh of capillaries. These vessels converge near the apex of each villus on a single, axially located villus vein. The central vein passes into the cryptic layer of the mucosa where it joins other venous channels which lead to the submucosal venous return system. In addition, there is an alternative venous return route in the form of a second set of venous channels that arise from the cryptic capillary plexus and cxtend to the venous channels leading to the submucosa. DISCUSSION In the classical description of the mucosal vascular architecture, the arterial supply to the villi is via a central villus arteriole while venous drainage is by a pair of marginal villus veins. The version presented here differs from the classical on two major points. Extensive fine dissection and microscopic examination of the intestinal mucosa has consistently failed to reveal an arterial route extending directly from the submucosa to the villi. The submucosal arterial distribution at all times was observed to terminate in the cryptic capillary plexus on the undersurface of the mucosa. In like manner, examination of the venous return system at all times showed jejunal and ileal villi to possess only a single, centrally located vein. 216 DAVID G . REYNOLDS, JACK BRIM AND THOMAS W. SIIEEHY Fig. 5 Jejunal nimosa dissected Bree along the subniucosal plane axd folded over to expose mucosal veins ( v ) which are bridged by veiiovcnous an?stomoses. At the bottom of the figure four mucosal veins join to form a large subinucosal vcnous channel. x 50. These observations suggest the vascular architecture of monkey intestinal mucosa to be closer in pattern to the tuft arrangement reported by Stohr ('01) and Szymonwicz ('02) than to Mall's fountain concept. Stohr and Szyrnonwiu describe the villus artery as giving rise to a tuft of capillaries at the base of each villus which, in turn, converge at the apex on an efferent vein. The mucosal vascular pattern presented here is intended only to describe the intestinal mucosa of the monkey. Sobin ('66) has shown that the circulatory patterns of individual organs or systems often differ between species. This observation is valid for the intestinal mucosa in that the circulatory patterns of the villi of the rat and rabbit, as well as gross villus morphology, differ markedly from that seen in the monkey. Instead of the cylindrical, finger-like shape of monkey villi, rat villi are broad, leaf-like structures and those in the rabbit vary from pyramidal structures in the upper intestine to slender, long, blade-like structures in the lower intestine. The vascular patterns of rat and rabbit villi resemble the classical version in that they possess both arterial and venous channels. Eat intestine. prepared in the manner described here, presents a picture that precisely supports Mohiuddin's description ('66). One or two arterial channels pass paraxially to the tip of each villus where one forms a large marginal capillary. The villus capillary network originates from this vessel and is drained through a large central vein. The width of rat and rabbit villi is quite variable within the different levels of the intestine. The broader structures commonly possess multiple arterial and venous channels. In addition, neither the cryptic layer is as thick nor the plexus as dense in the rat and rabbit a s they are in the monkey. Regional diffcrcnccs also exist within the monkey small intestinal mucosa. The description presented here is applicable only to jejunal and ileal mucosa. Duodenal villi VASCULAR ARCHITECTURS O F INTESTINAL MUCOSA 217 Fig. 6 Schematic of mucosal vascular architecture. A. Suhmucosal artcry; €3. cryptic capillary plexus; C . villus capillary net; D. central villus vein; E. secondary veins. of the monkey are broader than those from more distant areas of the small intestine and are often invested with two, and occasionally three, venous channels. In addition, the capillary nct of duodenal villi is of finer mesh than that of the lower regions. One subtle difference was observed between jejunal and ileal mucosae. The thickness and complexity of the cryptic plexus was greater in the jejunum than it was in the ileum. Fine dissection of the 2-color specimens often revealed a few channels of capillary nature that passed through the cryptic plexus with relatively few anastomoses. These vessels could often be followed directly into the villus capillary network as figure 3 demonstrates. Several lighter colored capillary channels can be seen to pass directly through the cryptic plexus and into the villus. This observation, plus the existance of the secondary venous return vessels, suggests the possibility of a regulatory mechanism that controls the distribution of blood in the mucosae. Such a mechanism would operate most efficiently in this system if the site of its action were at the secondary venous channels. If the secondary venous system were subjected to a constrictor influence, either neural or humornl in origin, the resistance to venous drainage of the mucosa would 218 DAVID G . REYNOLDS, JACK BRIM AND THOMAS W. SHEEHY increase. If this venous constriction were to occur without a reduction of arterial volume rate of flow, a balanced mucuosal flow could only be maintained if the volume of flow were to increase into the villus capillary nets. The overall result would be a passive shunting of blood into the villus capillary bed and ultimately an increase in venous return through the central villus vein. On the other hand, dilatation of the secondary veins would result in a drop in resistance through those channels and the bulk of the blood would be diverted through the cryptic plexus. A mechanism such as this might produce a separation of mucosal blood flow under different functional conditions. During active digestion and absorption, constriction of the secondary venous system would effectively increase blood flow through the villus capillaries. In a postabsorptive condition, the drop in resistance accompanying dilatation of these vessels would rcduce flow through the v d u s net by shunting it to the cryptic plexus. ACKNOWLEDGMENTS The authors would like to thank Lt. Jay H. Karsch for drawing the schematic diagram used in this report, Mr. John E. McClain for his microscopic photography and Mr. Dennis Townsend for technical assistance. LITERATURE CITED Bloom, W., and D. W. Fawcett 1962 Histology. W. B. Saunders, Philadelphia, pp. 454-456. Dcmis, D. J., and J. Brim 1965 A method of preparing thrce dimensional casts of the microcirculation of the skin. J. Invest. Derm., 45: 324-328. Hase, T. 1966 Heptaic microcirculatory changes i n acute and chronic carbon tetrachloride poisoning i n rats. Amer. J. Path., 49: 10691086. Jacobson, L. F., and R. J. Noer 1952 The vascular pattern of the intestinal villi i n various laboratory animals and man. Anat. Rcc., 114. 85-93. Mall, F. P. 1887 Die blut und lymphwege im dunndarm des hundes. Abh. d. Mat-phys. el. d. Kijnig. sachs. Gesell. d. Wiss., 1 4 : 153-200. Mohiuddin, A. 1966 Blood and lymph vessels in the jejunal villi of the white rat. Anat. Rec., 356: 83-90. Sobin, S. S., W. G . Frasher Jr. and H. M. Tremer 1962 Vasa vasorum of the pulmonary artery of the rabbit. Circ. Res., 11: 257-263. Sobin, S. S., W. G. Frasher Jr., H. M. Trcmer and G . G . Hadley 1963 The microcirculation of the tracheal mucosa. Angiology, 14: 165170. Sobin. S. S. 1965 Vascular inicction methods. 1n:’Meth. in Mcd. Rcs., edited by R. F. Rushmer, 11: 233-238. Sobin, S. S., and H. M. Tremer 1966 Functional geometry of the microcirculation. Fed. Proc., 25: 1741-1752. Spanncr, R. 1932 Neue hefunde uber die hlutwege der darmwand und ihre functionelle bedeutung. Morph. Jahrb., 69: 394-454. Stohr, P. 1901 Textbook of Histology. Translated by E 1,. Rilstein, Blakiston, Philadelphia, pp. 245-246. Szymonwicz, L. 1902 Textbook and Microscopic Anatomy of the Human Body. J. B. MacCallum, ed. Lea Brothers, Philadelphia. p. 191.