The Spleen As An Indicator Organ Of Hematopoietic Health

Few organs can match the versatility of the spleen. This small but forgotten organ is a powerhouse of prominent red cell activity such as filtration, production, and cellular immunity. Under normal circumstances, the organ cannot be felt or palpated on physical examination. This fist-shaped organ, located on the left side of the body under the rib cage, weighs about 8 ounces, is soft in texture, and receives 5% of the cardiac output per minute. The spleen, a blood-filled organ, consists of red pulp, white pulp, and the marginal zone. The function of the red pulp is primarily red cell filtration, whereas the white pulp deals with lymphocyte processing and the marginal zone with storage of white cells and platelets.

The Functions of the Spleen

There are four main tasks of the spleen that relate to red cell viability and the spleen's immunologic capability. The first function is the reservoir, or storage, function of the spleen. The spleen harbors one third of the circulating mass of platelets and one third of the granulocyte mass and may be able to mobilize platelets into the peripheral circulation as necessary. In the event of splenic rupture or trauma, large numbers of platelets may be spilled into the peripheral circulation. This event may predispose to unwanted clotting events, because platelets serve as catalysts for hemostasis. The second function of the spleen is the filtration function. The spleen has a unique inspection mechanism and examines each red cell and platelet for abnormalities and inclusions. Older red cells may lose their elasticity and deformability in the last days of their 120-day life span and are culled from the circulation by splenic phagocytes. Bilirubin, iron, and globin byproducts released through the culling process are recycled through the plasma and circulation.

Red cells that are filled with inclusions (Howell Jolly bodies, Heinz bodies, Pappenheimer bodies, etc.) are selectively reviewed and cleared. Inclusions are "pitted" and pulled from the red cell without destroying the cellular integrity, and red cells are left to continue their journey through the circulation.2 Antibody-coated red cells have their antibodies removed and usually reappear in the peripheral circulation as spherocytes, a smaller, more compact red cell structure with a shortened life span. One of the least appreciated roles of the spleen is the immunologic role. As the largest secondary lymphoid organ, the spleen plays a valuable role in the promotion of phagocytic activity for encapsulated organisms such as Haemophilus influenzae, Streptococcus pneumoniae, or Neisseria meningitidis. The spleen provides opsonizing antibodies, substances that strip the capsule from the bacterial surface. Once this is accomplished, the unencapsulated bacteria is more vulnerable to the phagocytic reticuloendothelial system (RES)3 and less able to mount an infection to the host system. Without a functioning spleen, this important function is negated and can lead to serious consequences, including fatality, for the infected individual. The final function of the spleen is its hematopoietic function, discussed earlier in this chapter.

Potential Risks of Splenectomy

Spleens that are enlarged, infarcted , or minimally functioning can cause difficulty for patients and these conditions are discussed in later chapters. Traditionally, the spleen was seen as an inconsequential organ, easily discarded and one that was not necessary to life function. While it is true that the splenectomy procedure may provide hematological benefit to patients who have problems with their spleen, it is equally true that individuals who do not have spleens have additional risks, as mentioned earlier. There have been reports in the literature of overwhelming postsplenectomy infections (OPSIs) that may occur years after the spleen has been removed. In most cases, these infections occur within 3 years, but they have been reported as long as 25 years after the splenectomy. Many individuals die from OPSIs or at the very least have multiorgan involvement. As an organ of the hematopoietic system, the spleen has

18 PartI • Basic Hematology Principles

Table 2.1 O Functions of the Spleen

Hematopoietic function Can produce white cell, red cells, and platelets if necessary Reservoir function One third of platelets and granulo-cytes are stored in the spleen

Filtration function Aging red cells are destroyed, spleen removes inclusion from red cells, if red cell membrane is less deformable or antibody-coated spleen presents a hostile environment leading to production of spherocytes Immunologic function Opsonizing antibodies produced, trapping and processing antigens from encapsulated organs immense capability and provides a high value and versatility (Table 2.1). If splenic removal is decided upon, the surgeon should leave some splenic tissue in place and carefully manage the asplenic patient; asplenic individuals represent a more vulnerable population.

THE BONE MARROW AND THE MYELOID:ERYTHROID RATIO

The bone marrow is one of the largest organs of the body, encompassing 3% to 6% of body weight and weighing 1500 g in the adult.4 It is hard to conceptualize the bone marrow as an organ, because it is not a solid organ that one can easily touch, measure, or weigh. Because bone marrow tissue is spread throughout the body, one can visualize it only in that context. It is composed of yellow marrow, red marrow, and an intricate supply of nutrients and blood vessels. Within this structure are erythroid cells (red cells), myeloid cells (white cells), and megakaryocytes (platelets) in various stages of maturation, along with osteoclasts, stoma, and fatty tissue.5 Mature cells enter the peripheral circulation via the bone marrow sinuses, a central structure lined with endothelial cells that provide passage for mature cells from extravascular sites to the circulation (Fig. 2.2). The cause and effect of hematological disease usually find root in the bone marrow, the central factory for production of all adult hematopoietic cells. In the first 18 years of life, bone marrow is spread throughout all of the major bones of the skeleton, especially the long bones. Gradually, as the body develops, the marrow is replaced by fat until the prime locations for bone marrow in the adult are the iliac crest, located in the pelvic area, and the sternum, located in the chest area. In terms of cellu-

larity, there is a unique ratio in the bone marrow termed the myeloid:erythroid (M:E) ratio. This numerical designation provides an approximation of the myeloid elements in the marrow and their precursor cells and the erythroid elements in the marrow and their precursor cells. The normal ratio of 3 to 4:1 reflects the relationship between production and life span of the various cell types. White cells have a much shorter life span than red cells, 6 to 10 hours for neutrophils as opposed to 120 days for erythrocytes,5 and thus need to be produced at a much higher rate for normal hematopoiesis.

ALTERATIONS IN THE MYELOID:ERYTHROID RATIO

The M:E ratio is sensitive to hematological factors that may impair red cell life span, inhibit overall production, or cause dramatic increases in a particular cell line. Each of these conditions reflects bone marrow dynamics through alterations of the M:E ratio. Many observations in the peripheral smear can be traced back to the patho-physiological events at the level of bone marrow. A perfect example of this is the bone marrow's response to anemia. As anemia develops and becomes more severe, the patient becomes symptomatic and the kidney senses hypoxia due to a decreased Hgb level. Tissue hypoxia stimulates an increased release of erythropoi-etin (EPO), a red cell-stimulating hormone, from the kidney. EPO travels through the circulation and binds with a receptor on the youngest of bone marrow precursor cells, the pronormoblast. The bone marrow has the capacity to expand production six to eight times in response to an anemic event.6 Consequently, the bone marrow delivers reticulocytes and nucleated red blood cells to the peripheral circulation prematurely if the kidney senses hypoxic stress. What will be observed in the peripheral blood smear is polychromasia (stress reticu-locytes, large polychromatophilic red cells) and nucleated red cells. Both of these cell types indicate that the bone marrow is regenerating in response to an event. This dynamic represents the harmony between bone marrow and peripheral circulation.

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