particularly when present in less common locations.

PHYSIOLOGY

The major functions of the spleen can be divided into two general categories of hematologic functions

and immunologic functions (Table 73-2).14 For hematologic functions, the spleen primarily is an organ

related to the destruction or clearance of the circulating blood cell elements as a normal physiologic

mechanism. This physiologic filtration function is increased in disease states that produce

hypersplenism. The spleen may play a minor role in hematopoiesis and storage of blood cells that can

be mobilized for the circulation with the predominantly stored cell being platelets predominantly

platelets. In terms of the immunologic functions, the spleen relates to the vascular system in many of

the same ways that lymph nodes relate to the lymphatic system. The white pulp and marginal zones are

most important for the immunologic functions, whereas the red pulp is primarily related to the

hematologic functions. However, the macrophages that line the cords or fill the cords in the red pulp

are clearly also important for immunosurveillance for intravascular pathogens.

Table 73-2 Normal Functions of the Spleen

3 The primary hematologic function of the spleen is removal of senescent erythrocytes or remodeling

of abnormal red blood cells with various deformities and the recycling of iron by splenic

macrophages.14 The average life span of a normal erythrocyte measured on clearance studies in humans

is estimated to be approximately 120 days.18 It is also estimated that the spleen destroys approximately

100 billion erythrocytes daily in the red pulp. The process of removal or phagocytosis of erythrocytes or

other blood cells is called culling. The blood flow patterns of the spleen lead to a hemoconcentrated

erythrocyte-laden fluid that enters the sinuses of the red pulp. Here a slow flow through the sinusoid

network with adjacent macrophage filled cords leads to the environment in which erythrocytes may

become trapped and then phagocytized by the macrophages. The precise mechanism by which senescent

red cells are identified for destruction in normal physiology is unclear. One hypothesis would be that

over the course of the life span of an erythrocyte, there is loss of either membrane elements or total

membrane material such that the red cells become less compliant and therefore become trapped in the

mesh of the sinusoids. A second hypothesis is that specific cell surface marker molecules may become

either more exposed or less available to allow identification of senescent cells targeted for destruction.

Pathologic destruction of red cells occurs in diseases such as hereditary spherocytosis or elliptocytosis in

which genetic defect creates abnormal red cell pliability limiting its passage through the red pulp.

Similarly, in sickle cell anemia, the genetic defect in the hemoglobin alters red cell shape and creates

destruction with clogging of the sinusoids. A second pathologic mechanism in which destruction of red

cells is increased is in disease processes in which there is an increase in red pulp volume, a condition

known as hypersplenism.

The second physiologic process involving circulating erythrocytes is remodeling or pitting that is

partial removal of the cell membrane typically associated with the cytoplasmic inclusions. Erythrocytes

with a remnant of the cell nucleus remaining pass more slowly through the splenic red pulp because of

their larger size.14 The nuclear remnant may be trapped passing through a small space in the spleen and

this solid particle that does not allow deformation gets pinched off in the process of pitting.

Intracytoplasmic inclusions include Howell–Jolly bodies that are nuclear remnants, Heinz bodies that

1988

are denatured hemoglobin, and Pappenheimer bodies that are iron granules.

The destruction of the other circulating cellular elements of the blood (platelets and leukocytes) is

more in the realm of pathophysiology of the spleen than normal physiologic function. The disease

processes in which these cells are removed are related to either autoantibodies to cell surface elements

or hypersplenism. If either platelets or white blood cells become coated with antibodies, the Fc portion

of the immunoglobulin will interact with the Fc receptors on the macrophages in the splenic cords

leading to phagocytosis of these cell types. With splenic enlargement from various causes of

hypersplenism, a similar process of destruction may occur even without any autoantibodies or defects in

the cells just because of an increase in splenic mass.

The spleen serves as a potential source for hematopoiesis of all cell types during gestation. In normal

humans, there is felt to be very little if any production of red cells, granulocytes, or platelets, which is

not the case in other mammals. In the white pulp of the spleen, there are germinal centers with

amplification and production of reactive lymphocytes. The cords of the spleen are filled with

macrophages and throughout normal adult life there may be production of lymphocytes and

macrophages in the spleen. In certain disease states, the spleen may develop the capacity for

erythropoiesis and myelopoiesis. The best example is agnogenic myeloid metaplasia (AMM), discussed

in more detail later. In this disease, the bone marrow is replaced with fibrotic scar and a portion of the

hematopoietic function of the marrow is taken over by the spleen that is typically quite enlarged.

The final hematologic function of the spleen may be as a reservoir of circulating cellular elements.15

In humans, the only significant cell type that is stored in the spleen is platelets and it is estimated that

30% of all platelets may reside in the spleen. This function may be more important than other mammals

particularly those with significant smooth muscle lining the capsule of the spleen that allows contracture

with expulsion of large numbers of stored cells as a physiologic response to injury.

4 The immunologic function of the spleen is primarily to generate an immune response to antigens

that are identified and cleared from the blood system. Either opsonized antigens or specific encapsulated

microorganisms are important examples of target antigens trapped by the spleen. The spleen is an ideal

environment for generation of either a cellular or humoral immune response. There are all of the

necessary cells types for stimulation of the immune response including phagocytic cells, dendritic cells,

T cells, and B cells that may form general follicles to generate specific antibody responses. These

interactions primarily occur in the marginal zone in the white pulp that may become quite enlarged and

hypertrophied during antigen stimulation. These cellular components and the structure of the germinal

follicles are essentially identical to those found in lymph node tissue that becomes enlarged in a similar

way with antigenic stimulation via microbes or antigens in the lymphatic system.

The spleen is also involved in nonspecific immune responses. It is the site of synthesis of both

properdin and tuftsin that are opsonins. Tuftsin is a small peptide that binds to the surface of

granulocytes and promotes phagocytic function by these cells.19 Properdin can initiate the alternate

pathway of complement activation that may be important in destruction of abnormal cells or bacteria

that are antibody bound. The spleen is not the only source of these nonspecific immune-enhancing

proteins and therefore splenectomy may lead to only a modest alteration in this function.

PATHOPHYSIOLOGY

There are characteristic responses that share many common features under the broad category of

hyposplenism and hypersplenism. These features highlight the normal physiologic functions of the

spleen and provide guidelines and influence clinical decision-making when managing patients after

splenectomy or in deciding which patients should undergo splenectomy.

Hyposplenism

By far, the most common cause of hyposplenism is surgical removal.20 Other explanations would be an

unusual situation of a congenitally small or absent spleen or acquired destruction of splenic tissue as

occurs in sickle cell anemia or celiac disease. The diagnosis can be verified by 99Tc-labeled spleen scan

or pitted red blood cell count. Pathophysiologic consequences of hyposplenism or the changes seen after

a splenectomy are predictable from the known functions of the spleen. There are hematologic changes

in the circulating cells that can be predicted from the splenic functions of culling, pitting, and as a

reservoir for platelets (Table 73-3). There are changes in the immunologic responses that are important

primarily in infants or young children, which can lead to the problem of overwhelming postsplenectomy

1989

sepsis. There are a variety of other causes for hyposplenism listed in Table 73-4.

Table 73-3 Hematologic Changes Postsplenectomy/Hyposplenic Condition

The changes in circulating blood cells after splenectomy in cases of hyposplenism affect the

erythrocytes, leukocytes, and platelets. Over time, the intracytoplasmic inclusions in the red cells that

are normally cleared by the spleen accumulate resulting in presence of Howell–Jolly bodies, Heinz

bodies, and Pappenheimer bodies as well as target cells with excess red blood cell membrane and

occasionally increase in the circulating nucleated red blood cells or reticulocytes. As the spleen is the

organ of storage for a large proportion of the platelets, a splenectomy often results in thrombocytosis

with platelet counts postsplenectomy ranging between 500,000 and up to one million in some cases.

This increased platelet count tends to be transient and may be a reflection of the fact that the spleen

while being a storage organ for platelets may not be a primary area of platelet destruction after the

typical half-life of 10 days. The immediate response after a splenectomy in white cells is leukocytosis

again reflecting storage of a large proportion of white cells in the spleen.21 As with the thrombocytosis,

this effect is transient but there may be long-term increases in the proportion of circulating lymphocytes

and monocytes after the splenectomy. Preserving even a small amount of spleen can preserve splenic

function in clearing senescent blood cells.22

Clinical sequelae of hyposplenism or following splenectomy are discussed in more detail at the end of

this chapter.

Hypersplenism

Hypersplenism is increased splenic function that is manifested clinically by the decrease in one or more

of the circulating blood elements. The specific criteria for hypersplenism are: (1) documented anemia,

thrombocytopenia, or leukopenia; (2) normal compensatory response by the bone marrow to correct the

cytopenia; and (3) correction of this cytopenia by splenectomy. Some definitions of hypersplenism may

also include the criteria for splenomegaly. This more restrictive definition would not necessarily

incorporate, however, diseases or disorders related to abnormalities in circulating blood cells such as

immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia. The second approach to

categorizing hypersplenism is to classify the disorders on the basis of whether the primary abnormality

is in the circulating blood cells versus in the spleen itself (Table 73-5). For either situation, the

pathophysiology is that the spleen is the site of destruction for one or more circulating blood elements.

In cases of significantly enlarged spleen, additional symptoms relate to mass effect from the spleen on

adjacent organs. The most important symptom is early satiety and weight loss as the stomach is

compressed between the liver and the enlarged spleen. There are a variety of causes of hypersplenism

that are typically neoplastic but may be related to primary blood cell dysfunction or abnormalities or

other condition such as portal hypertension due to cirrhosis or splenic vein thrombosis. Hypersplenism

is the most important indication for elective isolated splenectomy21 to reverse the cytopenia and often

to relieve compressive symptoms from splenomegaly.

Table 73-4 Causes/Disorders Associated with Hyposplenism

1990

Table 73-5 Causes of Hypersplenism

SURGICAL TREATMENT FOR DISEASES RELATING TO THE SPLEEN

Until fairly recently, the only pertinent operation to discuss in relationship to disease involving the

spleen was open splenectomy. Appreciation of the increased risk of infection in inpatients who are

asplenic or hyposplenic in the late 1960s and the early 1970s led to two new surgical procedures. First,

there was an interest in splenic preservation in cases of trauma with procedures including splenorrhaphy

and other types of ways to save damaged spleen. Second, procedures to do partial splenectomy were

developed primarily for elective surgery in which hypersplenisim existed but a complete splenectomy

was not necessary and there were advantages to partial splenectomy. The most recent change in surgery

of the spleen relates to the explosion in the minimally invasive surgery that has happened over the past

25 years.23 The spleen is very susceptible to a laparoscopic excision and recent reports have utilized

laparoscopic splenectomy for virtually all indications including to remove massive spleens. Despite its

increasing utilization in most major centers, though, laparoscopic splenectomy still appears to constitute

only a minority of the splenectomy procedures performed nationally.

1991