Microcirculatory pathways in normal human spleen, demonstrated by scanning electron microscopy of corrosion casts

Abstract

Confusion regarding microcirculatory pathways in normal human spleen has arisen due to extrapolation from pathological material and from other mammalian spleens, not to mention difficulties in tracing intricate three-dimensional routes from the study of thin sections or cut surfaces of tissue. We examined microcirculatory pathways in normal human spleens freshly obtained from organ transplant donors. A modified corrosion casting procedure was used to obtain an open view of vessels and their connections. Our results demonstrate: 1) "arteriolar-capillary bundles" within lymphatic nodules and extensive branching of arterioles in the marginal zone (MZ); 2) the marginal sinus around lymphatic nodules; 3) the peri-marginal cavernous sinus (PMCS) outside the MZ or immediately adjacent to the nodule itself; the PMCS receives flow via ellipsoid sheaths and MZ, or directly from arterial capillaries, and drains into venous sinuses; 4) fast pathways for flow into venous sinuses via ellipsoid sheaths; 5) arterial capillary terminations in the reticular meshwork of the red pulp or MZ ("open" circulation); direct connections to venous sinuses also occur ("closed" circulation), although rarely; and 6) numerous open-ended venous sinuses in the MZ, allowing a large proportion of the splenic inflow to bypass the red cell filtration sites in the reticular meshwork and at venous sinus walls.

Ultrastructure of human spleen in transmission and scanning electron microscope

“…From sinuses the blood runs into veins of the red pulp, from there to trabecular veins to vena lienalis. The open system of the blood circulation prevails in the human spleen, while the smaller part runs in the closed system Brozman & Jakubovský 1989;Kashimura 1985;Schmidt et al 1988). Kashimura & Shibata (1989) described even three types of spleen circulation with different functions.…”

In Vivo Splenic Clearance Correlates with In Vitro Deformability of Red Blood Cells from Plasmodium yoelii-Infected Mice

“…In humans, 76 to 79% of the spleen is made of red pulp, a dense meshwork composed of splenic cords and splenic sinuses. Previous studies on different animal (dog, cat, and rat) models revealed that from 90% (3)(4)(5) to 10% (6) of total splenic blood undergo so-called "closed circulation," during which RBCs traverse venous sinuses bypassing the red pulp; open circulation occurs in the remaining blood, whereby RBCs enter the reticular meshwork, following slow microcirculation (1,7). The structural and mechanical quality of the RBCs is ascertained by the mechanical constraint imposed by the meshwork in the red pulp, where old and abnormal RBCs that are less deformable are retained and eventually removed by phagocytosis (7).…”

“…Careful consideration was also given to the structural similarities and differences between human and mouse spleens. Human spleen is sinusal (29); human RBCs (8 m) have to squeeze through the interendothelial slits (ϳ1 m) (16) in venous sinus walls, which act as a mechanical filter to abnormal or stiffened RBCs (5). In comparison, though mouse spleen is arguably classified as nonsinusal (5), the fenestrations in the walls of mouse pulp venules are so small (1 to 3 m) (30) compared to murine RBCs (ϳ6 m) that they still function just like venous sinus and mechanically trap less-deformable RBCs (31).…”

B Cells Are Crucial for Both Development and Maintenance of the Splenic Marginal Zone

“…1). This marginal zone receives a substantial part of the blood flow that enters the spleen, because the sinus it comprises is connected to the arteriolar network of the organ (2). Blood-borne lymphocytes that arrive in the marginal zone are able to enter the white pulp by extravasating the marginal sinus through fenestrated mucosal addressin cellular adhesion molecule-1 ϩ (MAdCAM-1 ϩ ) 3 sinus lining cells (3).…”