Page 2600 - Hematology_ Basic Principles and Practice ( PDFDrive )

C H A P T E R 160

THE SPLEEN AND ITS DISORDERS

Nathan T. Connell, Susan B. Shurin, and Fred Schiffman

Galen described the spleen as the “organ of mystery,” with functions infections), peak during puberty, and involute in adulthood. Unin-
related to mood and good or ill humors. It was not until the 18th fected adults with an intact immune system usually do not show
century that the spleen’s relationship to the immune and hematologic evidence of germinal centers. The secondary germinal center is
systems was appreciated. The complexities of splenic function con- comprised of a mantle zone of B lymphocytes surrounding the fol-
tinue to be the focus of research and observation. Although many of licle. Antigen trapping and processing take place in the marginal zone
its functions overlap with or can be assumed by other organs, it is an of the white pulp.
important regulator of immune function and hematologic homeosta- The red pulp of the spleen consists of vascular sinuses, the cords
sis. The spleen efficiently phagocytoses erythrocytes, recycles iron, of Billroth, and the terminal branches of the penicilliary arteries (Fig.
+
recognizes and destroys pathogens, and induces adaptive immune 160.2). Vascular sinuses are lined with CD8 littoral endothelial cells
responses. An appreciation for the subtleties of its anatomy and that resemble endothelial cells with long processes and a basement
function is important for the physician evaluating patients with many membrane with ring fibers that attach to macrophage-derived den-
hematologic, immunologic, hepatic, and infectious diseases. dritic processes. No tight junctions or interdigitations connect the
cytoplasmic processes. Intact leukocytes, erythrocytes, and platelets
are able to squeeze through the potential spaces between these cells
NORMAL SPLENIC ANATOMY AND FUNCTION and between the ring fibers (Fig. 160.3). Processes of the reticular
cells of the cords of Billroth are outside the sinus walls. Endothelial
Embryology cells line pulp veins but not the cords.
The reticular structure of the spleen facilitates its immune
The spleen arises from the mesoderm and, by the ninth week of gesta- response. Venous sinus endothelial cells contain a plasma membrane-
tion, layers of the left dorsal mesogastrium condense with the appear- associated network of stress fibers composed of actin and myosin-like
ance of blood vessels. Sheaths are formed around arterioles by reticular filaments. These filaments may cross the plasma membrane and insert
1
cells and fibers. Macrophages are present and develop phagocytic into the mesh-like basement membrane. As the fibers tense, they
function by the end of the first trimester. Lymphocytes appear during create fenestrations through which erythrocytes must pass if they
the fourth month, and a formal delineation between red and white hope to continue their journey. With age, erythrocytes lose the ability
pulp can be identified by the sixth month. Germinal centers do not to deform their shape and navigate the pathways created by these
develop during fetal development, but primitive inactive follicles are fibers and will not be able to continue into the circulation. The limi-
evident at birth. In mice, the homeobox gene Tlx1 (formerly known tation is similar for erythrocytes containing parasitic infections. This
as Hox11), which controls the genesis of the splanchnic mesodermal mechanism, combined with mannose receptors and Toll-like recep-
2
plate, is essential for development of the spleen. Both the basic tors, helps the infrastructure of the spleen play a role in the host’s
helix-loop-helix transcription factor capsulin and the Wilms tumor overall immune response.
suppressor 1 (WT1) gene are necessary for formation of the spleen. Circulation of blood through red pulp lined with endothelial-like
The genetic basis for development of the human spleen is less well littoral cells represents a rapid and closed circulation. Circulation into
understood. The spleen is capable of supporting hematopoiesis the cords is slower and open, thereby permitting the macrophages
during fetal life and, in a variety of pathologic states, postnatally. The lining the cord to remove damaged or aged cells.
circulation of primitive hematopoietic stem cells in peripheral blood Accessory spleens are present in up to a third of the population
during prenatal life through birth makes it difficult to distinguish and result from failure of precursor cells to fuse during embryologic
hematopoiesis arising from stem cells in the spleen as opposed to the development. Usually, they receive blood flow from the splenic artery
incidental presence of hematopoietic cells within the circulation. and are located near the spleen, but they can be distant and mistaken
for a tumor when noted on imaging studies or physical examination.
Accessory spleens may develop similar conditions as the spleen proper
Anatomy and should be considered within the differential diagnosis for patients
who have continued abnormalities after splenectomy.
3,4
The spleen is the body’s largest filter of the blood. Located directly
below the diaphragm and adjacent to the stomach, it is covered by a
fibrous capsule with blood vessels, lymphatics, and nerves coated by Functions
peritoneal mesothelium. The splenic artery arises from the celiac axis,
enters the capsule at the hilum, and branches into trabecular arteries. The functions of the spleen and their anatomic locations are sum-
The trabecular arteries then branch into central arteries and enter the marized in Table 160.1. Correlation with anatomy and histology are
white pulp. The periarterial lymphatic sheath consists of a cuff of T shown in Fig. 160.4
lymphocytes, plasma cells, and macrophages around the central arter-
ies. As the arteries branch, the sheath narrows. B-lymphocyte clusters
appear in follicles along the periarterial lymphatic sheath at arterial The Red Pulp
branch points (Fig. 160.1).
The components of the white pulp are connected by a reticular Splenic macrophages dominate the function of the red pulp and are
network and supporting stromal cells. On the cut surface of the responsible for filtering blood, removing bacteria, and recycling iron.
normal spleen, white pulp is visible as white nodules approximately
1–2 mm in diameter, although their size varies with age and antigenic Removal of Damaged and Aged Formed Elements
stimulation. The nodules are fully developed at birth, increase in The venous system of the red pulp enables it to filter whole blood,
size during childhood (especially following immunizations and removing senescent erythrocytes and other blood cells. Arterial

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