Talk:Paper - Development of the blood vessels of the mammary gland in the rabbit (1915)
DEVELOPMENT OF THE BLOOD VESSELS OF THE MAMMARY GLAND IN THE RABBIT
H. M. WAHL
From the Anatomical Department, University of Wisconsin
The mammary glands receive their blood supply from the superficial blood vessels of the thoraco-abdominal walls. The chief arteries distributing blood to these superficial vessels in the rabbit are the thoraco-epigastric (external mammary), arising from the subclavian, and the superficial epigastric arising from the femoral. The internal mammary furnishes several small branches which pass between the ribs to the skin and a large epigastric branch. A small branch from the hypogastric artery passes to the region of the inguinal gland. There is a fairly constant branch from the lateral thoracic to the thoraco-epigastric. The intercostals furnish little of the blood supply. From the main arterial trunks branches are freely distributed. Anastomoses are frequent between the branches.
The larger veins as a rule parallel the arteries. The thoracoepigastric vein is an exception in that it enters the axillary rather than the subclavian vein. The smaller veins and arteries are less apt than the main trunks to parallel one another. The terminal branches interdigitate in such a way as to insure an even distribution of blood in the capillaries.
The main branches lie in the subcutis superficial to the cutaneous muscle. From these vessels rami pass, on the one hand, toward the skin, on the other, out over the surface of the musculature, on which an extensive rectangular plexus is formed. From both sets of branches, as well as from the main vessels, rami pass into the mammary glands.
During embryonic development the cutaneous vessels are formed from the capillary plexus which is developed on the
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outer side of the anlage of the body wall as this extends forward at the expense of the membrana reuniens to enclose the thoracoabdominal viscera. This plexus at first drains forward through the membrana reuniens into the umbilical vein, but later the thoraco-epigastric vein becomes differentiated so as to drain the plexus into the main vein of the arm. From a similar plexus on the inner surface of the body wall, which at first drains into the cardinal veins, later also into the subclavian and femoral veins, the intercostal, internal mammary and deep epigastric vessels are differentiated. Between these and the superficial vessels numerous anastomoses exist. At a later period the territory of the thoraco-epigastric vein comes to drain into the femoral vein as well as into the axillary vein and the arteries corresponding to the superficial veins are formed.^
Although the mammary line arises comparatively early it appears to exert no influence on the formation of the chief ventral cutaneous vessels. The latter are fonned in response to the needs for more direct vascular connections in the ventral region of the abdominal wall as the umbilical veins change their courses and the distance from the dorsal axis increases.
The first noticeable influence of the gland region on the cutaneous vessels appears at the period when the individual gland anlages begin to differentiate in the mammary line. At this time in the deep layer of the skin the branches of the thoracoepigastric vein spread out widely and anastomose. Superficial to these larger branches there is a network of smaller capillaries. This network becomes especially well developed about the lenticular thickenings of the epidermis which mark the anlages of the glands (fig. 1). As the epithelial buds of the ducts project downwards and the connective tissue begins to condense about their bulb-like extremities a special capillary plexus develops in this connective tissue sheath.
By the time the ducts extend laterally from the primitive gland anlage veins and arteries are differentiated in the capillary
^ Helen W. Smith, The development of the superficial veins of the body-wall in the pig. Am. Jour. Anat., vol. 9, p. 439, 1909; F. T. Lewis, The development of the lymphatic system in rabbits. Am. Jour. Anat., vol. 10, p. 113, 1905.
BLOOD VESSELS OF THE MAMMARY GLAND
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Fig. 1 Cross-section through the skin of a rabbit embryo 23 mm. long, showing the aniage of a mammary gland and sections of several blood vessels. Magn. 66 diam.
Fig. 2 Mammary gland of a newborn rabbit, seen from below; the epidermis and nipple have been removed from the piece of skin in which the gland lies. The skin has been lightly stained with carmine, cleared and mounted in balsam. The blood vessels are injected; the veins are shown lighter colored than the arteries; no attempt has been made to show the capillaries. The smaller ducts of the gland have been bent back over the nipple area in mounting the specimen and are shown darker than the rest of the gland ; length of longest duct, 2 mm. Magn. 8 diam.
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plexus surrounding this anlage. These vessels may be readily followed in a new-born rabbit (fig. 2). At this period the ducts spread out a short distance from the nipple anlage and have narrow necks and dilated extremities. The chief superficial blood vessels and their branches are distributed essentially as in the adult. From the vascular trunks and their main branches and from the chief branches to the superficial layer of the dermis and to the cutaneous muscle lying near the gland anlage rami may be followed to the nipple region and upwards in the connective tissue surrounding the necks of the ducts into a plexus lying immediately beneath the epidermis covering the anlage of the nipple. As a rule, at this period the arterial and venous rami take somewhat independent courses, although frequently they parallel one another for a part of their course. The longer ducts extend toward the main blood vessels and the rami coming from these run parallel to the ducts. Frequently an arteriole will run on one side of a duct, a venule on the other side. Capillary plexuses surround the ducts, but are less well developed about the necks of the ducts than about their expanded extremities.
Two months after birth the ducts have extended considerably further from the nipple region and show many bulging projections, the anlages of branches (fig. 3). The vascular supply of the gland is much elaborated. Special vessels to the nipple region supply the capillary plexus about the necks of the ducts and that part of the ducts lying near the nipple, while other vessels from the cutaneous and muscular plexuses are beginning to supply the extremities of the ducts. The nipple branches are long slender tortuous vessels which give off few rami until near the nipple. Some of them lie superficial to and others beneath the free parts of the ducts. At the base of the nipple they turn upwards toward the apex of the nipple which at this period is a small bullet shaped projection. Usually one or more main rami may be followed into the arterial rete about the mouth of the ducts. Some of these rami lie at the periphery of the group of ducts in the nipple, others in the midst of the group. Both sets send branches to the capillary plexus about the necks and mouths
Fig. 3 Mammary gland of a rabbit two months old, prepared like that shown in figure 2. The ducts are cut off near the base of the nipple; only a few of the larger blood vessels are shown; length of longest duct 5 mm. Magn. 8 diam.
Fig. 4 Two main ducts and their branches of a mammary gland of a fullgrown virgin rabbit, prepared as described tor figure 2. A tew of the arteries supplying the gland are shown; length of longest duct 10 mm. Magn. 8 diam.
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of the ducts. The peripheral vessels also send branches into the integument surrounding the nipple. For each of the larger arterial rami there is usually a vein which takes a corresponding course but does not always run close to the artery. About the free extremities of the ducts as they extend outwards from the nipple region a rich capillary plexus is developed. Near the tips of the ducts this capillary plexus is continuous with that of the surrounding stroma, but toward the nipple it exhibits a greater independence. As this independence is established there become developed in the capillary plexus of the stroma arterioles and venules which supply the capillary plexus of the ducts. First an arteriole is differentiated, then a venule, so that the capillary plexus of the ducts is supplied alternately by arterioles and venules as one passes from the nipple region outwards. At the growing tips of the ducts one usually finds either a developing arteriole or a developing venule. The branches which supply these arterioles and venules arise directly from the main subcutaneous vessels, and from the overlying cutaneous or from the underlying muscular vascular plexuses. The chief venous and arterial rami supplying the venules and arterioles to a given part of the duct may parallel one another or the venule may come from a direction different from that of the arteriole.
In the fullgrown virgin rabbit (fig. 4) the ducts have ramified out extensively from the nipple region. The glands are from 2 to 3 cm. in diameter. The ducts branch in a plane parallel with the surface of the body but no branches project perpendicular to this plane. The blood supply of the nipple region corresponds essentially with that described for the rabbit at two months, but the plexus about the necks of the ducts is more fully developed. As a rule, the terminal venules and arterioles enter the plexus on opposite sides of a given segment of the duct. The arteries and veins distributed to the free parts of the ducts are far more extensively developed than at the preceding stage, but otherwise are similar in origin and distribution. As the ducts extend outwards branches from the superficial cutaneous vessels and the superficial muscular plexus are called upon more and more for a vascular supply, although the chief subcutaneous vessels also
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furnish new branches to them. The alternation of venules and arterioles continues as at the preceding stage. In the capillary plexus about the ducts, however, venules and arterioles are beginning to appear. The venules are better developed than the arterioles and exhibit a greater tendency to form longitudinal trunks accompanying the main ducts and joining the main vessels which pass to the gland directly from the chief subcutaneous vessels.
During the early stages of pregnancy the ducts expand rapidly and their ramification increases (fig. 5). If the territory supplied by a single main duct and its various branches be called a lobe it soon becomes impossible on mere gross inspection to distinguish one lobe clearly from another owing to the interdigitation of branches from neighboring lobes. The territories of the chief branches of the main ducts similarly become difficult to distinguish clearly as sub-lobes. As pregnancy advances the ducts of the smaller compound units of structure, the lobules, begin to appear on the ends and sides of the main ducts and their branches. The first lobular ducts to appear may arise from a plane perpendicular to the skin on both the superficial and deep surfaces of the ducts. The lobular ducts may be simple or compound. The simple ducts arise as solid bulbular processes which elongate and become hollowed out. The sides of these ducts become studded with knob-like processes which later expand into alveoli. The compound lobular ducts give rise to branches of one or more orders and these, in turn, become studded by alveoli.
Meanwhile, in the nipple region the necks of the ducts become much enlarged to form the lacteal sinuses, although in sections the walls appear irregular and collapsed. The mouths of the ducts, hitherto expanded and funnel-shaped, become greatly constricted. At the base of the nipple the ducts are likewise constricted but beyond here they again dilate.
At first the vascular development proceeds essentially along the lines described in the growing animal. The capillary plexuses about the ducts, however, become much more richly developed than before and the development of arterioles and venules in
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these plexuses becomes much more active, the differentiation of the veins of the ducts continuing as before to exceed that of the arteries.
The subcutaneous vessels in the region of the gland and all of the vessels supplied to the gland meanwhile increase rapidly in size. Not only do the vessels enlarge in diameter, but they also elongate with the outward growth of the ducts and send rami to the branches which arise from the ducts. The new ducts are supplied in part by branches thus derived from the vessels of the parent ducts and in part by new vessels developed in the capillary plexus of the surrounding stroma. As mentioned above, there is a greater tendency for the new veins than the arteries to be derived from the preexisting duct vessels.
In the latter part of pregnancy the chief interest lies in the development of the vascular supply of the glandular lobules. At first the anlage of the lobule is surrounded by a network of capillaries continuous with the capillaries of the duct. As the lobular anlage enlarges the surrounding capillary plexus becomes more richly developed and one or more arterioles and venules are developed between it and the arteries and veins of the ducts. As the alveolar ducts develop at the periphery of the lobular ducts the same process is repeated, venules and arterioles for the alveoli being developed between the capillary plexus about the alveoli and the vessels of the lobule (fig. 6). Frequently, however, the arterioles, and less frequently the venules, of the capillary plexus join vessels which approach the lobule from the side opposite the duct. Both the veins and the arteries may extend into a lobule from the extremity opposite the duct. The venules and arterioles supplied to the alveoli both however, almost invariably extend from the neck of the alveolus outwards into the capillary plexus surrounding it.
During lactation the gland still further increases in size owing to the expansion of the existing alveoli and the formation of new ones. Between the expanded secreting alveoli the connective tissue becomes very slight in amount. The ducts beiome greatly distended with milk. There is a great elaboration and
F'iff. .") A duct and its branches of a mammary gland of a rabbit in the early stages oi pregnancy, prepared as described imder figure 2. The smaller blood vessels are not shown; length of longest duct 15 mm. Magn. 8 diam.
Fig. 6 Cross-section through a duct and its branches of a mammary gland of a rabbit during lactation. Magn. 17 diam.
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enrichment of the vascular supply of the gland, but the essential features are as above described (fig. 6) .
Within two weeks after weaning the gland appears much thinner than during lactation owing chiefly to disappearance of milk from the ducts and to the retrograde metamorphosis which becomes well marked first in the alveoli and later in the ducts. The alveoli first shrink in size, then the alveolar cells degenerate and are absorbed, but usually a duct stem remains as a small group of epithelial cells with merely a small lumen or no lumen. The stroma appears relatively greatly increased as the alveoli disappear. Different parts of the same gland undergo quite unequal retrograde metamorphosis. The alveoli of one duct may disappear, while along another duct they may appear to be still in the secreting stage. Alveoli of this kind may persist for at least several months after lactation. The walls of the main ducts and their branches first collapse as the contained milk secretion is absorbed and then gradually shrink in size.
As the alveoli are absorbed the surrounding capillaries disappear so that in the lobule the relatively thick-walled venules and arterioles seem disproportionately large compared with the capillary field which they supply. The capillaries about the ducts likewise in part disappear. The various arteries and veins of the gland appear for a time tortuous and shrunken, but gradually they come to resemble more and more the vessels of the gland of the virgin adult. Several characteristic differences, however, remain. The ducts are much longer and more ramified than in the virgin animal and the number of veins and arteries supplying them is greater. The larger arteries are more regularly accompanied by veins and the large veins by arteries.
To sum up briefly: The blood supply of the gland during development and rest appears in the main to be secondary to the blood supply of the skin and the subcutaneous muscles, but during functional activity it becomes more independent, the blood supply of the alveoli being connected with the vessels of the ducts and to a large extent, at least, independent of that of the stroma. The irregularity in the retrograde metamorphosis of the gland and the changes in the blood supply are suggestive from the standpoint of cancer formation.