The vasculature of the human penisA reexamination of the morphological basis for the polster theory of erection.код для вставкиСкачать
THE ANATOMICAL RECORD 203:475-484 (1982) The Vasculature of the Human Penis: A Reexamination of the Morphological Basis for the Polster Theory of Erection JOANN McCONNELL, GEORGE S. BENSON. AND WALDEMAR A. SCHMIDT Department of Neurobiology and Anatomy (J.M.1,Department of Surgery (Division of Urology1 (G.S.E.1, and Department of Pathology and Laboratory Medicine (Division of Surgical Pathology1 (W.A.S.),The University of Texas Medical School, Houston, Texas 77025 ABSTRACT The morphology of human penile blood vessels has been studied to characterize columns of smooth muscle found in the intima. Although previous workers (Kiss, 1921; Conti, 1952)termed these intimal pads or polsters and concluded that they were actively responsible for the production of erection, more recent work has questioned these conclusions (Benson et al., 1980; Newman and Tchertkoff, 1980). Serial sections were taken throughout the length of the penis from 11 cadavers and stained with various histopathological stains. Numerous polster-like structures were found, but all could be identified as either branch points in vessels, intimal cushions located at branch points, or arteriosclerotic lesions at various stages of development. None of these structures seem capable of functioning in the manner attributed to them by Conti (1952)and others. Furthermore, comparison of the structures found in the present study to illustrations of polsters in Conti’s paper suggest that these are identical. The present study refutes the polster theory of erection and leaves open to further question the mechanisms involved in the control of blood flow into and within the penis. Myoendothelial cells, clusters of smooth muscle cells within the intima of human blood vessels, were first noted over a century ago, but controversy over the function of these structures continues today. Some have concluded that they control the flow of blood through various organs (Bjorkman, 1947;Conti, 1952; Hibbs et al., 1958; Puchtler et al., 1969; Meloan et al., 1972; Elias, 1977), while others see them as evidence of pathological processes in the arterial wall (Haust and More, 1958; Haust et al., 1960; Balis et al., 1964; Rodgers et al., 1968; Ross and Glomset, 1977; Irey et al., 1978). The most elaborate functional role proposed for these structures is related to penile erection. Early in this century, Von Ebner (1900)described muscular cushions and ridges in human penile vasculature (“polsterartige”) and Kiss (1921)finding the same structures, agreed that they might play a role in the process of erection. Conti (1952).in a histological study of penile tissue from 20 normal individuals varying in age from newborn to 77 years, found 0003-276X/82/2034-0475$0300 1982 ALAN K LISS. INC many columns of primarily longitudinally oriented, intimal smooth muscle in both arteries and veins; he termed these “polsters,” or intimal cushions, pads or bands, using these terms interchangeably. He provided a detailed explanation for the production of tumescence and maintenance of detumescence based on the function of these structures, which increased and decreased in size to control the flow of blood through the penile vessels. Although Conti’s study was strictly anatomical, and the physiological conclusions were purely theoretical, the polster theory of erection has been well accepted for many years. In earlier studies of human and other mammalian penes (McConnellet al., 1979; Benson et al., 1980),we were unable to find polsters in any of the specimens. However, since the human penile tissue in these studies came from young males who had received estrogen on a daily basis for at least a year prior to undergoReceived July 8. 1981: accepted April 1. 1982 476 J.McCONNELL, G.S. BENSON, AND W.A. SCHMIDT ing transsexual operations, it seemed advisable to examine a more heterogeneous, nonestrogen-treated population. In a subsequent study of biopsy tissue from six (nontranssexual) males of varying ages (2-62 years; Benson et al., 1981). we still found no evidence of polsters as described by Conti (1952). Structures resembling polsters were found, but were identified as branch points of vessels, intimal smooth muscle cushions, or arteriosclerotic lesions in various stages of development, none of which seem capable of the function attributed to polsters by Conti (1952);arteriosclerotic lesions are clearly pathologic, and subendothelial cushions have been implicated as prearteriosclerotic (Wilens, 1951; Lauper et al., 1975; Kottke and Subbiah, 1978). Nevertheless, as these were negative data, and since the study involved a limited population (only six patients, the oldest of which was 62), and biopsies which were generally small, superficial, and primarily from or near the glans, it was considered necessary to make a more extensive survey. The present study localizes and characterizes the smooth muscle columns found in blood vessels throughout the entire penis, includes tissue from males over a wide range of ages for comparison with the work of Conti (1952),and critically evaluates Conti’s findings and theory. Serial sections were cut at 10-12 pm through half of each block (ca. 50 sections). Every 10th section was stained with hematoxylin and eosin (H and E) for preliminary scanning; this examination of the H and E sections was done without the scanner’s knowledge of the age of the individual. Whenever a polster-like structure was seen in an H and E section, the neighboring sections were treated with more specific staining methods. These included phosphotungstic acid hematoxylin (PTAH), periodic acid-schiff (PAS)with and without diastase digestion, Snook’sreticulin, Masson’s trichrome, Verhoff-van Gieson’s elastica, Alizarin Red S. and von Kossa’s calcium method. RESULTS Polster-like structures containing longitudinal smooth muscle cells were observed in both intra- and extracorporal blood vessels of the penis, but upon careful examination of serial sections, most of these were identified as either branch points of vessels (Fig. l),intimal cushions (Fig. 2), or arteriosclerotic lesions in various stages of development (Fig. 3); the greatest number of cushions was seen in large extracorporal veins and arterioles. Large clusters of smooth muscle seen in the walls of veins of the corpus spongiosum may be similar to cushions or may be individual variations in venous structure; nevertheless, they can be of MATERIALS AND METHODS little significance in the erectile process as the The entire penis, from the pubic arch to and corpus spongiosum does not contribute to including the glans penis, was obtained from erection. 11cadavers varying in age from 38 to 83 years Several specimens demonstrated no arterial (Table 1). The penes were hemisected, cut cushions or arteriosclerosis, a finding unretransversely into blocks 5-7 mm in thickness, lated to the age of the individual. The and processed for routine paraffin embedding. respective ages and the incidence of polster- T A B L E 1. Extent and character of intimal thickenings in penile tissue from 11 cadavers. .~ Age of individual ~. 38 56 61 61 66 72 73 73 74 81 83 Cushions - ~~ Some arteriosclerotic changes . ~~~ ~ ~~ Moderate arteriosclerosis ~~~~ + ++ + + + + + + + + + ++ + + + + + + + + ‘Calcification of the wall of small vessels similar t o t h a t seen in dlabetics. Advanced atheroma ~~~ ~ ~ Other arteriosclerotic lesions .- ++ + + +‘ - VASCULATURE OFTHE HUMAN PENIS Fig. 1. A tributary of the dorsal vein of the penis containing a polster-like structure (arrow)which is actually the point a t which a smaller tributary enters. A large blood clot (C)nearly fills the lumen of the larger vein. 61-year-old male. FTAH. x 50. 477 Fig. 2. Branch of the dorsal artery of the penis containing intimal cushions (arrowheads) a t the point where two small arterioles (arrow) exit. 49-year-old male. Verhoff-van Gieson. x 132. like structures found in each is shown in Table increased length of the penis during erection, 1; note that the greatest number of arterio- the intima may appear unusually thick in some sclerotic lesions appear in some of the younger sections. These intimal thickenings (Fig. 5) are men. Many of these structures are similar in easily differentiated from arteriosclerotic appearance to Conti's illustrations of polsters changes by studying serial sections using sev(Fig. 4). eral criteria, and special stains for elastic fiNonpathologic or typical arteries were en- bers, reticular fibers, mucopolysaccharides, countered most frequently. These arteries are and smooth muscle cells. Arteriosclerotic composed of three morphologically distinct lesions in their early stages and intimal layers, the tunica adventitia, media, and cushions are characterized by intimal intima. The tunica adventitia normally con- thickening from edema and smooth muscle intains loose connective tissue, blood vessels, filtration (Fig. 6A). In advanced stages of the and small nerves. The tunica media is com- disease, the intima is significantly thickened, posed of smooth muscle cells embedded in con- containing more smooth muscle, extensive colnective tissue and bordered by a layer of elastic lagen, and fibrotic tissue (Fig. 6B),and there is fibers, the external elastic lamina. The normal fragmentation and duplication of the internal intima consists of a single layer of endothelial and occasionally, the external elastic lamina cells bounded by a narrow band of connective (Figs. 6B, C). The most advanced lesions tissue, often containing a few smooth muscle demonstrate foamy histiocytes and fibrin decells, and a single layer of elastic fibers, the posits (Fig. 6D). Most of the polster-like structures seen in internal elastic lamina. However, since penile blood vessels are ex- our study represent lesions at various stages in tremely tortuous, in order to accommodate the the currently accepted sequence of the patho- 478 J.McCONNELL. G.S. BENSON. AND W.A. S C H M I D T VASCUIATUKE OF T H E HUMAN PENIS genesis of atherosclerosis as described by Haust (1971), Ross and Glomset (1977), and Kottke and Subbiah (1978).Structures identified as atherosclerotic lesions in our tissue were compared with Conti’sillustrations (1952) demonstrating polsters. As reported earlier (Benson et al., 1981),the structures were virtually identical (Figs. 3,4,6). DISCUSSION During the mid 1880s, several histological investigators, including Henle (1841), Remak (1850), and Koelliker (1854),reported finding cells that resembled smooth muscle within the intima of blood vessels. In addition, Koelliker stressed the resemblance of these cells to the endothelium, and Henle concluded that the morphological similarities suggested a developmental relationship between the two. Langhans (1886)reasoned that the intima was connective tissue, and thus the cells in the subendothelial layers must be considered fibroblasts or fibrocytes. For over a century, there was disagreement over the identity as well as the origin of these cells. Finally, using the electron microscope, Balis et al. (1964) and Reale and Ruska (1965) demonstrated conclusively that the subendothelial cells are smooth muscle. The origin of these cells, however, remains unclear. Curiously, the subendothelial cells closest to the internal elastic lamina have always been considered to be smooth muscle, and were noted to occur frequently near areas when the lamina was split or frayed. These clusters of cells were thought to originate from the tunica Fig. 3. Penile arteries demonstrating polster-like arteriosclerotic lesions a t various stages of development. A) Central artery of the corpus cavernosum (deep artery of the penis) demonstrating several regions of intimal smooth muscle proliferation and edema (arrows). 83-year-old male. H and E. x 96. B) Branch of the dorsal artery of the penis with a small area of arteriosclerotic intimal thickening (arrow).This Verhoff-van Gieson stain shows the disruption and duplication of the internal elastic lamina typical of arteriosclerosis. 83-year-old male. x 70. C) Branch of the dorsal artery of the penis with two more advanced arteriosclerotic lesions (arrows).These structures contain longitudinally oriented smooth muscle interspersed with some disorganized smooth muscle cells a s well as collagen and fibrin, and show some disruption of the internal elastic lamina (arrowhead). 81-year-old male. Masson trichrome. x 64. D) Advanced atheroma in a branch of the dorsal artery of the penis. The lumen has been significantly decreased by proliferation of smooth muscle, collagen, and fibrin in the intima. Note the duplication and thickening of the internal elastic lamina. 66-year-old male. Verhoff-van Gieson. x 88. 479 media. Thoma (1883) proposed that such smooth muscle appeared within the intima after disruption of normal hemodynamics. Borst and Enderlen (1909), studying wound healing in blood vessels, particularly vascular transplants, found that many cells resembling smooth muscle appeared in the intima within a few days after suturing. After histological studies, they concluded that these arose by transformation of endothelial cells. Electronmicroscopic studies have likewise demonstrated that smooth muscle seen in arteriosclerotic lesions may also arise from the endothelium (Haust et al., 1960). How the subendothelial smooth muscle relates to wound healing or to the disease process of arteriosclerosis is still not fully understood. I t has been suggested, however, that these muscle clusters may represent a reaction to the stresses of normal blood flow, thus being a response to injury (Neufeld et al., 1962). and an attempt to counteract the decreased contractility of the weakened vessel wall (Haust et al., 1960). This same function might be expected in a vessel which is in the process of healing after transplantation. During the past 20 years, careful study of autopsy specimens correlated with results of various experimental studies and the use of animal models have revealed the major elements and details of the pathogenesis of atherosclerosis. The major current theories of atherogenesis share the belief that the lesions begin as localized, excessive accumulations of intimal smooth muscle (intimal thickenings, intimal cushions, intimal hyperplasia). The theories differ, however, in what initiates these accumulations and what makes them grow. It is not yet clear whether the increased smooth muscle is derived from endothelial cells, from a relatively small preexistent population of intimal smooth muscle, or from smooth muscle cells of the tunica media which migrate into the intima and subsequently proliferate. Regardless, the intimal smooth muscle cells proliferate in response to endothelial injury, and such smooth muscle clusters are generally considered to be a sign of vascular disease (Kottke and Subbiah, 1978; Irey et al., 1978). In experimental studies, injury to or removal of the endothelium from an artery stimulates the migration of smooth muscle cells from the media. The endothelium starts to regenerate in 3-5 days, and the smooth muscle cells appear shortly thereafter. A t the end of 2 weeks, the endothelium is completely regenerated, but the intima is thickened considerably by a p proximately 5-10 layers of smooth muscle 480 J.McCONNELL, G.S. BENSON, AND W.A. SCHMIDT Fig. 4. Illustrations of “polsters” from Conti’s paper (1952).Left, A, B (from Figs. 9A. D). Intracavernous branches of the deep artery of the penis (central artery). Right, C, D (from Figs. 8B. D). Branches of the dorsal artery of the pe- nis. Hollborn elastic stain. (Reprinted from Conti G: Lerection du penis humain et ses bases morphologico-vasculaires. Acta Anat.. 14.217, 1952. with permission from S. Karger AG. Basel.). cells which remain there permanently (Ross and Glomset, 1973). The injury site is easily distinguished from an area of normal intima which contains only a few smooth muscle cells. Endothelial damage also can be accomplished by injecting fatty acids into the ear vein of rabbits (Sedar et al., 1978), and intimal thickenings composed of smooth muscle cells occur when rabbits are fed cholesterol (Parker, 1960). Further, in diseased segments of blood vessels replaced by tubes of artificial fibers, the pseudointima which subsequently lines these fabric grafts is composed of connective tissue and smooth muscle cells covered by neo-endotheli- um (Florey et al., 1961); indeed, a common problem in these grafts is intimal proliferation to such an extent that it causes lategraft occlusion (Kottke and Subbiah, 1978). Considering the above, it is not difficult to comprehend that the incidence of intimal smooth muscle increases with age, and that there is a greater chance of finding atherosclerotic plaques in an elderly individual. Almost all of the above data on intimal hyperlasia and atherosclerosis was not available at the time Conti (1952)put forth his theory of erection. Conti’s work was part of an extensive effort to demonstrate that blood vessels were VASCULATURE OFTHE HUMAN PENIS 481 Fig. 5 . Small branch of the central artery demonstrating a thickened and uneven intima due to the tangential cut of this very tortuous arteriole. 73-year-old male. H and E. x 280. not passive carriers of blood, but were active in regulating blood flow. Bucciante, one of the leaders of this school, had previously shown that elastic fibers and smooth muscle in blood vessels increased with the age of the individual, and had concluded that these were adaptations to improve the local flow of blood (cf.Conti, 1952). Conti’s report of clusters of intimal smooth muscle which he named “polsters” or “polsterkissen”(German, cushions) in penile arteries and veins of newborn and infant males added support to the belief that these were functional structures. These early-appearing clusters of smooth muscle were found most often at branch points of vessels, and are still generally considered to be “intimal cushions.” The difference, however, is that they are no longer accepted as functional elements since they have been implicated in arterial disease. (A distinct problem arises with respect to terminology in this field. Von Ebner, Kiss, Conti, and others employed the terms “polsterkissen” and “coussinet,” both of which translate as “cushion,” and used these terms interchangeably with words meaning “pad,” “column,” “fascicle,” and “cluster” when referring to intimal thickenings. “Polster” in the present terminology refers specifically to those structures of widely varying size in the penile vasculature which have varying amounts of smooth muscle, edema, and connective tissue, and which are supposed to regulate blood flow to effect erection and detumescence. “Intimal cushions,” however, are generally considered to be regions in the vascular intima with some smooth muscle proliferation and minimal edema and connective tissue. Some consider the latter structures to be the first sign of arteriosclerosis, but others feel that these are regions which may develop into arteriosclerotic lesions.) Although penile tissue from very young individuals often contains a few of these structures, their number is variable (Newman and Tchertkoff, 1980). The incidence of cushions generally increases with age, and they appear related to arteriosclerosis in both man and laboratory animals (Wilens, 1951; Neufeld et al., 1962; Kottke and Subbiah, 1978); most cushions are found at branch points of vessels which is also the site of early atherosclerotic lesions. Nevertheless, the precise relationship of cushions to atherosclerotic plaques has not been determined conclusively, and it would appear that all intimal cushions do not become atherosclerotic plaques and that all plaques do not develop in preexisting intimal cushions (Kottke and Subbiah, 1978). Fig. 6. High power photomicrographs of arteriosclerotic lesions in penile arteries. A) Enlargement of small lesion on left of artery in Figure 3C showing some longitudinally oriented and some disorganized smooth muscle (arrows),edema in the intima, and gaps in the internal elastic lamina (arrowheads). 81-year-old male. Masson trichrome. x 320. B) Nearby section from the artery shown in Figure 3D demonstrating smooth muscle surrounded by extensive collagen and some fibrin deposits. 66-year-old male. Masson trichrome. x 190. C. Section adjacent to t h a t shown in Figure 6B. The Verhoff-van Gieson stain demonstrates that duplication, thickening, and occasional fragmentation of the internal elastic lamina. x 190. D) Advanced atheromatous lesions in a branch of the dorsal artery of the penis contain ing foamy histiocytes (arrows). fibrin (arrowhead). and general disruption of the intima. 49-year-old male. H. and E. x 340. VASCULATUKEOFTHE HUMAN PENIS Conti’s (1952)study of human penile vasculature and his explanation for penile erection have been completely accepted by the medical community even though his hernodynamic conclusions were based solely on histologic data. In his examination of penile tissue from 20 individuals varying in age from birth to 77 years, he found many instances of intimal smooth muscle clusters and columns. From their organization, he assumed that they were functional elements subserving the control of blood flow and postulated a detailed schema for tumescence and detumescence. Although Conti’s paper was published less than 30 years ago, the photomicrographs showed little detail, and many illustrations were drawings of blood vessels taken from earlier papers. A detailed description of the smooth muscle columns seen in various individuals with various histological stains was provided, but no information was given about the innervation of these structures. We consider these micrographs, drawings, and descriptions to depict branch points, arterial cushions (which may or may not be pre-atherosclerotic), and atherosclerotic plaques in various stages of development. Conti (1952), in fact, characterized a well-developed polster as having duplication of the internal elastic lamina as well as many intimal smooth muscle cells surrounded by collagen and other connective tissue elements. These are now considered indicative of an intermediate stage of atherosclerotic plaque formation. That polsters are actually evidence of atherosclerosis is further supported by the findings of Ruzbarsky and Michal (1977)who found that the most characteristic change in the penile vasculature due to age and diabetes is “fibrosis of the polsters and fibrotic proliferation of the intima in other areas.” They described the gradual replacement of the smooth muscle cells, the “functional element” of polsters, by inelastic collagenous connective tissue, and the thickening, fragmentation, and eventual fibrosis of elastic membranes. Endothelial defects often occurred over these fibrotic polsters and, in some cases, the intima was obliterated by fibrotic proliferations within the polster. Calcium deposits were usually found within polsters which showed advanced stages of fibrosis. Such changes describe exactly the presently accepted sequence of the pathogenesis of atherosclerosis (Ross and Glomset, 1977). Furthermore, if polsters were to function as hypothesized, they would have to receive innervation from their periphery or be otherwise 483 stimulated to change shape. As yet, no information showing the innervation of these structures has appeared in the literature or been obtained in this laboratory. Indeed, to stimulate these muscle clusters, neurotransmitters would have to diffuse through the entire thickness of the vessel wall or through the endothelium since nerve fibers are found only in the vascular adventitia (Keatinge, 1979). In conclusion, the present study presents data refuting the polster threory of erection and leaves open to further question the physiologic mechanisms responsible for control of the regional blood flow of the penis. ACKNOWLEDGMENTS The authors wish to express their appreciation for the excellent technical assistance of Ms. Donna Harrison who made significant contributions to the analysis of the data as well as the preparation of the histological material and the photographic reproductions . This investigation was supported in part by a NIAMDD Clinical Investigatior Award ( # 5 KO8 AM00824-02)from the National Institute of Arthritis, Metabolic and Digestive Diseases awarded to George S. Benson, M.D. LITERATURE CITED Balis, J.U., M.D. Haust, and R.H. More (1964) Electronmicroscopic studies in human atherosclerosis. Exp. Mo. Pathol., 3:511-525. Benson, G.S., J.A. McConnell. L.I. Lipshultz. J.N. Corriere. and J oe Wood (1980) Neurornorphology and neuropharmacology of the human penis. J. Clin. Invest..65:506-513. Benson, G.S.. J.A. McConnell. and W.A. Schmidt (1981) Penile “polsters”: Functional structures or atherosclerotic changes? J. Urol., 125:800-803. Bjorkman. S.E. 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