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864 Part VI: The Erythrocyte Chapter 56: Hypersplenism and Hyposplenism 865

STRUCTURE AND FUNCTIONAL as well as decreased clearance by macrophages of antibody-coated platelets
ORGANIZATION through the Fc recognition function of its large macrophage population.
Splenomegaly increases the proportion of blood channeled
The normal adult spleen weighs 135 ± 30 g and has a blood flow that is through the red pulp. 13,21 Spleen enlargement may result from expansion
approximately 5 percent of the cardiac output. In addition to serving as of the red pulp compartment with increased blood flow; extramedullary
a filter, the spleen plays a role in innate and adaptive immunity and pro- hematopoiesis, notable in primary myelofibrosis; hyperplasia or neo-
tection against microbes. The spleen is composed of white pulp, a mar- plasia involving the white pulp, such as in infectious mononucleosis or
ginal zone, and red pulp. The spleen’s principal structure is organized lymphoma; or histiophagocytic hyperplasia.
around an arborizing array of arterioles that branch and narrow until The increased size of the filtering bed is more pronounced when
they terminate in either (1) the stroma of cords, forming the open circu- the splenomegaly is caused by congestion as in portal hypertension than
lation, or (2) the sinusoids, forming the closed circulation of the spleen when it is caused by cellular infiltration as in leukemias, extramedullary
(Chap. 6). The cordal elements include histiocytes, antigen-presenting hematopoiesis, or amyloidosis. Even in space-occupying disorders such
cells, pericytes, fibroblasts, and other cells necessary to maintain the as Gaucher disease and primary myelofibrosis, splenomegaly may be
13
discontinuous basal lamina that separates cords from sinusoid lumen. associated with hypersplenic sequestration of normal cells.
Lymphatic tissue is inconspicuous and found in T-cell–rich zones in the Splenomegaly increases the vascular surface area and thereby the
periarteriolar lymphoid sheaths. marginated neutrophil pool. 18,19 Platelets are especially likely to be seques-
The arterial vascular tree, which is lined by conventional CD31+ tered in an enlarged spleen. However, sequestered white cells and plate-
and CD34+ endothelial cells, branches into arterioles that terminate lets survive in the spleen and may be available when increased demand
abruptly in caps of cordal macrophages. Blood cells must pass clusters requires neutrophils or platelets, although their release may be slow. 22
13
of macrophages to enter the sinusoids. The sinusoids, the origin of Some patients with anemia and splenomegaly have a relative ery-
the venous circulation, are lined by specialized cells having combined thropoietin deficiency. In one study of cirrhotic patients, 30 percent
23
phagocytic and endothelial activities and a distinctive CD31+, CD34−, had a blunted erythropoietin response to anemia. Dilution of red cells
24
CD68+, CD8+ phenotype. A principal function of the spleen is to serve in an expanded plasma volume is another commonly cited cause of a
as a filter, removing aged or defective red cells and foreign particles decreased blood hemoglobin concentration, although some studies
25
by macrophages. This function is facilitated by diverting part of the do not demonstrate hemodilution. Iron deficiency associated with
26
splenic blood supply into the red pulp, where the blood slowly perco- chronic blood loss, folic acid and vitamin B deficiency, and increased
12
lates through the nonendothelialized mesh studded with macrophages. red cell destruction are frequently investigated, although rarely found in
Abnormal or senescent red cells and pathogens undergo phagocytosis patients with liver disease. Red cells are destroyed prematurely in the
27
by the macrophages. The blood then reenters the circulation through red pulp in the setting of splenomegaly, but only rarely does this explain
narrow slits, measuring 1 to 3 μm, in the endothelium of the venous the anemia. 28
sinuses. The bulk of the blood is rapidly channeled through vessels that Varying amounts of erythrophagocytosis are present, reflecting
link the arterioles with the venous sinuses. This blood is not filtered or the normal culling of senescent red cells. Erythrophagocytosis increases
modified. 14 as a result of hemolytic anemia and viral infections, and in alloimmu-
Approximately one-third of platelets are normally sequestered in nized transfusion recipients. Macrophages within the sinusoids con-
the spleen. In many animals, such as dogs and horses, the red pulp is tain red cell fragments. When the process is pronounced, the littoral
15
a reservoir for red cells, and splenic contraction provides the red cell cells become cuboidal and stand out on the basement membrane
16
volume with a functionally important boost. In humans, however, the (“hobnails”). Sickle cell disease and red cell membrane disorders such as
splenic capsule is poorly contractile, and the spleen does not store red hereditary spherocytosis lead to sequestration of the poorly deformed
cells to any significant degree. Although margination of neutrophils red cells in the cords but little extrasinusoidal erythrophagocytosis is
17
18
occurs in the spleen, it is unclear to what degree it occurs in that site. seen, in contrast to immune hemolytic anemia where macrophage ery-
Granulocyte colony-stimulating factor (G-CSF) administered to cir- throphagocytosis is prominent. 13
rhotic patients caused a rise in the blood neutrophil count; thereafter, The increased blood flow from an enlarged spleen expands the
indium scans of the spleen were performed, which did not show signifi- splenic and portal veins. A significant increase in portal venous pressure
cant uptake by white cells. 19 may occur when hepatic vessel compliance is decreased, as in cirrhosis
The slow transit of blood through the red pulp permits macro- or myelofibrosis. This process initiates a vicious cycle in which portal
phages to recognize and destroy antibody- or complement-coated red hypertension contributes to splenomegaly, organ enlargement leads to
cells and microorganisms, and to ingest poorly deformable red cells or increased arterial blood flow, which, in turn, increases portal pressure.
particles retained mechanically by the narrow exit slits in the venous Table 56–1 lists causes of splenomegaly, and Table 56–2 lists causes
sinuses. The white pulp plays a major role in adaptive immunity. The of massive splenic enlargement.
spleen is involved in the phagocytosis of encapsulated bacteria includ-
ing Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria CLINICAL FEATURES
meningitidis.
Slight to moderate enlargement of the spleen usually does not produce
local symptoms. Even massive splenomegaly can be well tolerated if it
PATHOPHYSIOLOGY develops gradually. However, not infrequently, the patient complains of
Filtration and elimination of defective cells occur notably in hered- a sagging feeling or other types of abdominal discomfort, early satiety
itary abnormalities of the red cell membranes, such as spherocytosis, from gastric encroachment, and trouble sleeping on one side. Pleuritic
elliptocytosis, or stomatocytosis, or with antibody-coated red cells, pain in the left upper quadrant or referred to the left shoulder may
neutrophils, or platelets. In these circumstances, cytopenias of varying accompany splenic infarcts, which may be recurrent.
severity may ensue. The spleen not only removes antibody-coated cells, In children with sickle cell anemia or patients with malaria, the
but also produces antibodies, especially antiplatelet antibodies. Thus, spleen may become acutely enlarged and painful as a result of a sud-
20
the benefits of splenectomy in immune thrombocytopenic purpura den increase in red cell pooling and sequestration. These sequestration
is a result of both the decreased production of antiplatelet antibodies crises are characterized by sudden aggravation of the anemia. Splenic

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