Anatomy and Physiology of the Spleen

PART

FOUR

Spleen Anatomy and Physiology of the Spleen Luise I.M. Pernar 

|

  Ali Tavakkoli

T

he spleen has been a source of intrigue and mystery since ancient times, and its anatomy and function have been contemplated by ancient Egyptians and Chinese as far back as 1550 bc. The spleen was variably thought to be associated with emotions, and both ill temper and glee have been thought to arise from the spleen. Across centuries the true significance of the spleen was questioned by a variety of physicians, ranging from Galen to Princelsus, and it was not until the turn of the 20th century that the role of the spleen started to be understood.1–3 Surgery to remove the spleen preceded a good understanding of its function: the first reported splenectomy was performed in 1549 by Zaccarella of Italy, and the first documented splenectomy, performed in 1826, is credited to Quitterbaum of Germany. The first laparoscopic splenectomy was not performed until 1991 by Delaitre and Maignien of France.4 Although the first splenectomies were performed with little knowledge of the function of the organ, our increased awareness of the role of the spleen as an immunologic organ has changed the preoperative preparation of patients due to undergo an elective splenectomy. The spleen serves important functions as a secondary lymphoid tissue, contributing through phagocytosis and orchestration of humoral and cellular immunity.5 The spleen is also associated with multiple nonimmunologic functions, serving as the differentiation site for platelets, reticulocytes, and monocytes; the reservoir for granulocytes and erythrocytes; and the removal site for aged and deformed red blood cells.5,6 The spleen additionally plays a role in embryogenesis of the pancreas7 and may serve as a reservoir for islet cell precursors.8 This function appears to be clinically significant because impaired glucose tolerance after splenectomy has been observed.9 The spleen also is a source of other stem cell precursors, specifically those expressing HOX11, a protooncogene, and thus may also be involved in oncogenesis of leukemia.10

EMBRYOLOGY The splenic primordium appears during the fifth week of development as a mesodermal proliferation between the two leaves of the dorsal mesogastrium. In the early stages of development the splenic mesenchyme is also adherent to the dorsal pancreatic bud.11 As the stomach

CHAPTER

136 

rotates around an anteroposterior axis, with its caudal portion moving upward and to the right and its cephalic portion moving downward and to the left, a portion of the dorsal mesogastrium eventually fuses with the peritoneum of the posterior abdominal wall. The splenic mesenchyme then separates from the pancreas, and the spleen remains intraperitoneal.11 The splenic primordium is eventually infiltrated by lymphoid cells. Hematopoiesis is prominent in the spleen from the third to the fifth months of embryonic life. By the fourth month, the red pulp structure begins to appear.6

ANATOMY The spleen lies underneath the ninth, tenth, and eleventh ribs on the left, measures 7 to 13 cm in length, and weighs an average of 150 g, although normal weights range from 70 to 250 g and may decrease with age. Splenomegaly is usually considered if splenic weight is greater than 500 g or length greater than 15 cm; massive splenomegaly is defined as splenic weight exceeding 1500 g. The spleen becomes palpable underneath the left costal margin in instances where its size is at least twice normal. The spleen is asymmetric in shape with a smooth convex portion abutting the diaphragm and a concave surface medially (Fig. 136.1).12,13 Externally, the spleen is enveloped almost entirely by peritoneum, which is adherent to the splenic capsule and forms several ligaments to surrounding structures. The surgically significant ligaments are the gastrosplenic ligament, containing the short gastric vessels, and the splenocolic and splenorenal ligaments that tether the spleen to the colon and kidney, respectively (Fig. 136.2). The splenic ligaments develop collateral vessels in cases of portal hypertension. Knowledge of these ligaments is critical because they need to be carefully divided when mobilizing the spleen. The gastrosplenic ligament is particularly important because it contains the splenic vessels, which are also often accompanied by the tails of the pancreas. Knowledge of the location of the tail of the pancreas is clinically relevant during a splenectomy to help avoid pancreatic injury. Computed tomography (CT) image analysis has shown that the distance between the pancreatic tail and the splenic hilum averages 3.4 ± 1.5 cm and is typically at least 1 cm. Therefore surgeons

1591

Anatomy and Physiology of the Spleen  CHAPTER 136 1591.e1

ABSTRACT The spleen is the largest lymphoid organ in the body. It also functions as a site for blood cell storage and quality control. Surgeons most frequently are called upon to perform urgent splenectomy in the setting of trauma, but numerous indications also exist for elective splenectomy. An understanding of the spleen’s anatomy and physiologic function is essential to perform splenectomy safely and to appropriately care for patients after splenectomy.

KEYWORDS Splenic artery; splenic vein; red pulp; white pulp; marginal zone; overwhelming postsplenectomy infection

1592

SECTION III  Pancreas, Biliary Tract, Liver, and Spleen 1

1

3

2

21 4 5

20 19

6

6 5 16

4

17 10

3

11

15 13

18

12 13

1

2

11 5

7

14 9 7

10

8 8

9

8

FIGURE 136.1  Gross anatomy photograph of the relationship of the spleen to the diaphragm and other organs. The left upper abdominal and lower anterior thoracic walls have been removed, and part of the diaphragm (1) has been turned upward to show the spleen in its normal position, lying adjacent to the stomach (2) and colon (9), with the lower part against the kidney. The spleen is connected to the stomach by the gastrosplenic ligament (3) and the colon by the splenocolic ligament. The organ’s convex shape results from the gastric impression (4) and its position against the thoracic wall (11). When viewed from the front, one can see the spleen’s superior border (5), notch (6), diaphragmatic surface (7), and inferior border (8). Also shown here is the costodiaphragmatic recess (10). (From McMinn RMH, Hutchings RT, Pegington J, Abrahams PH. Color Atlas of Human Anatomy. 3rd ed. St Louis: Mosby-Year Book; 1993:230–231.)

need to stay within 1 cm of the splenic hilum during a splenectomy to avoid injury to the pancreas.11,13,14 Approximately 20% of the population has one or more accessory spleens, usually located within the splenic hilar region. Accessory spleens may also be found in the pancreas, omentum, and even in the pelvis and reproductive glands (Fig. 136.3).15 A technetium 99m (99mTc)-labeled red blood cell scan can be used to help localize accessory spleens16 if complete splenectomy is mandatory, as in surgical management of immune thrombocytopenic purpura (ITP). The incidence of accessory spleens may be as high as 30% in individuals with hematologic pathology.13

BLOOD SUPPLY, LYMPHATIC DRAINAGE, AND INNERVATION The spleen receives approximately 5% of the cardiac output, via the splenic artery, the largest of the three branches of the celiac trunk (Fig. 136.4). However, the

FIGURE 136.2  Gross anatomy photograph of the spleen in transverse section (level of the 12th thoracic and 1st lumbar vertebrae) illustrating the anatomic relationship of the spleen to the stomach, colon, and kidney, and the clinically important splenic ligaments. (1) Left lobe of liver, (2) stomach, (3) diaphragm, (4) gastrosplenic ligament, (5) costodiaphragmatic recess of pleura, (6) ninth rib, (7) tenth rib, (8) peritoneum of greater sac, (9) spleen, (10) left kidney, (11) posterior layer of splenorenal ligament, (12) tail of pancreas, (13) splenic artery, (14) splenic vein, (15) anterior layer of splenorenal ligament, (16) lesser sac, (17) left suprarenal gland, (18) intervertebral disc, (19) abdominal aorta, (20) celiac trunk, and (21) left gastric artery. (From McMinn RMH, Hutchings RT, Pegington J, Abrahams PH. Color Atlas of Human Anatomy. 3rd ed. St Louis: Mosby-Year Book; 1993:230–231.)

spleen also receives some accessory supply from branches of the left gastroepiploic artery. The splenic artery is a tortuous artery that lies posterior to the superior border of the body of the pancreas, forming multiple coils, and eventually divides into two or three main branches that penetrate through the hilum of the spleen. There are two main patterns of splenic artery anatomy, the magistral type, in which a long splenic artery trunk reaches close to the splenic hilum before dividing into branches, and the distributed type, in which there is a short splenic artery trunk with branching far from the splenic hilum. The distributive type is the more common variation.13,17 The splenic artery branches in turn divide into segmental arteries that enter along the splenic trabeculae (Fig. 136.5). There is little collateral circulation at this level, and occlusion of one of these arteries usually is associated with infarction of the corresponding region of the spleen, a phenomenon seen in embolic diseases. Segmental arteries give rise to trabecular arteries, which in turn, and by means of perpendicular branches, give origin to central arteries.12 There is an ongoing debate regarding the paths of blood flow after it enters the spleen. In general, it is thought that the blood takes two paths: a fast (closed) circulation that takes the blood directly from the arterioles to venules and has a predominance

Anatomy and Physiology of the Spleen  CHAPTER 136 

1593

referred to as Kehr sign, is observed, particularly after splenic rupture.18 1 2 3 4 5 6

7 8

9 10

11

FIGURE 136.3  Schematic of common locations of accessory spleens. (1) Gastrosplenic ligament, (2) splenic hilum, (3) tail of the pancreas, (4) splenocolic ligament, (5) left transverse mesocolon, (6) greater omentum along the greater curvature of the stomach, (7) mesentery, (8) left mesocolon, (9) left ovary, (10) Douglas pouch, and (11) left testis. (From Gigot JF, Lengele B, Gianello P, Etienne J, Claeys N. Present status of laparoscopic splenectomy for hematologic diseases: certitudes and unresolved issues. Semin Laparosc Surg. 1998;5:147–167.)

of plasma, and a slower (open) circulation that takes the blood through the pulp. The majority (90%) of flow is in fact of the slow (open) type, which exposes the circulating cells and erythrocytes to splenic macrophages in the red pulp. Irrespective of the circulation in the spleen, veins leave the spleen through fibrous bands, or trabeculae, attached to the capsule, and coalesce to form the splenic vein. The splenic vein joins the superior mesenteric vein behind the neck of the pancreas to give origin to the portal vein (see Fig. 136.4). Lymphatic drainage follows the vasculature. Drainage is into the splenic hilar and celiac nodes via the pancreaticosplenic lymph nodes.12 The splenic nervous plexus is formed by branches of the celiac plexus, left celiac ganglion, and right vagus. It runs together with the splenic artery and is composed mainly of sympathetic fibers that reach blood vessels and nonstriated muscle of the capsule and trabeculae. Referred pain from the spleen to the left shoulder, commonly

HISTOLOGY OF THE SPLEEN The human spleen is composed of red and white pulp, which are separated by a thin marginal zone (Fig. 136.6). The red pulp makes up approximately 75% of the spleen and is predominantly composed of splenic cords, capillaries, and venous sinuses, which express endothelial markers (e.g., clotting factor VIII), within loose reticular tissue. This richly vascular, specialized portion of the spleen enables it to function as a filter of blood. The white pulp consists of lymphoid follicles (mostly B lymphocytes) and the periarterial lymphoid sheath (PALS) (mostly T lymphocytes). These, along with the lymphoid, nonfiltering red pulp (both B and T lymphocytes), are responsible for the spleen’s immunologic function. Although comprising only a minority of the overall mass, this lymphoid compartment plays an important role in the early immunologic response against blood-borne antigens and is the compartment primarily responsible for splenic involvement with lymphoproliferative disorders.5,6,19 The spleen’s lymphoid cells express characteristic cluster designation (CD) and other markers that confer specific immunophenotypes to various regions of the spleen. Table 136.1 shows significant markers of lymphoid tissue. A full discussion is beyond the scope of this chapter, but it suffices to say that studying the immunophenotyopes of cells in lymphomas can determine if they are related to the spleen.

FUNCTIONS OF THE SPLEEN It is helpful to think about the functions of the spleen under the following headings, where we will also review expected changes following a surgical splenectomy.

ERYTHROCYTE QUALITY CONTROL AND REMOVAL OF DEFECTIVE RED CELLS The red pulp is responsible for “quality control” of erythrocytes. This is achieved through pitting and culling. Pitting refers to the removal of nondeformable intracellular substances from deformable cells. The rigid element is removed while the deformable cytoplasmic mass returns to the general circulation. In the case of red cells, this involves removal of Heinz bodies (denatured intracellular hemoglobulin), Howell-Jolly bodies, and hemosiderin granules from red cells. Absence of this function following splenectomy explains the presence of circulating erythrocytes with Howell-Jolly and Pappenheimer bodies (siderotic granules). Indeed, the number of pitted cells is inversely proportional to splenic function. Pits represent vesicles containing hemoglobin, ferritin, and mitochondrial remnants. Under normal circumstances, there are less than 2% pitted cells.20 Culling is the term applied to the spleen’s ability to remove aged red cells at the end of their 120-day life cycle. As the red cell ages, it loses its membrane integrity and therefore deformability, which result in their phagocytosis by splenic macrophages.20 However, the spleen is not the only site for red cell destruction, and there is no difference

1594

SECTION III  Pancreas, Biliary Tract, Liver, and Spleen Common hepatic artery Left gastric artery

Short gastric arteries

Aorta Portal vein

Celiac trunk

Superior polar artery

Splenic artery

Splenic vein

Superior mesenteric vein

Left gastroepiploic Inferior polar artery artery

FIGURE 136.4  Arterial and venous supply of the spleen.

in red cell survival following splenectomy. Platelets and leukocytes are not predominantly removed by the spleen as they age but rather marginate and die in other tissues.

Hilus

Capsule

}

Red pulp: Sinusoid Cord

Trabecular artery

Trabecula

White pulp

In health, the spleen is not an important reservoir for blood cells but is so for platelets. Approximately one-third of the platelet mass is pooled in the spleen. With splenomegaly, a large proportion of platelets are sequestered in the spleen (up to 80%) and this, along with increased platelet destruction in an enlarged spleen, can result in thrombocytopenia. The role of the spleen in platelet storage also explains the increase in platelet count following a splenectomy.20 Neutrophils have a short half-life, and majority either migrate at random into tissues or are destroyed within 24 hours. Hypersplenic states can be associated with neutropenia because of accelerated sequestration of granulocytes or because of enhanced splenic removal of altered granulocytes, as seen in immune neutropenias.

HEMATOPOIESIS

Trabecular vein Lymphoid nodule

Closed theory

Sinusoids

POOLING

Open theory

FIGURE 136.5  Details of the splenic structure, highlighting relationship of the white and red pulp to trabecular arteries and closed and open circulation. (From Groom AC. Microcirculatory Society Eugene M. Landis award lecture—microcirculation of the spleen: new concepts, new challenges. Microvasc Res. 1987;34:270.)

The spleen has an important hematopoietic function in fetal life. Active hematopoiesis can be seen into the third trimester. Late in the second trimester hematopoietic function is transitioned to the bone marrow. In general, splenic hematopoiesis does not occur in healthy adults. Under certain pathologic conditions in which the bone marrow is unable to produce blood cells (e.g., myelofibrosis) or is unable to meet production demands (e.g., chronic hemolytic anemia), extramedullary hematopoiesis in the spleen increases. Typically the resulting cells will be more immature than those produced by the bone marrow.20

ANTIBODY SYNTHESIS IN THE WHITE PULP In addition to the phagocytosis of antibody-coated cells, the immunologic functions of the spleen include antibody synthesis (especially immunoglobulin M). Foreign antigens are filtered in the white pulp and presented to lymphoid

Anatomy and Physiology of the Spleen  CHAPTER 136 

WHITE PULP FOLLICLES

RED PULP

A

RP

WP

B

MANTLE ZONE

MARGINAL ZONE GERMINAL CENTER

C FIGURE 136.6  Normal human spleen on hematoxylin-eosin staining. (A) Low-power photomicrograph showing relationship and relative proportions of red and white pulp. (B) Medium-power photomicrograph (arrow indicates periarterial lymphoid sheath). (C) High-power photomicrograph showing detailed secondary follicle architecture. RP, Red pulp; WP, white pulp (secondary follicle).

cells, where an immunoglobulin response is mounted, leading to release of antibodies.

FILTRATION Macrophages residing in the splenic parenchyma, particularly in the marginal zone, capture cellular and

1595

noncellular material from blood, including encapsulated bacteria, such as pneumococci and meningococci, and destroy them. Splenic macrophages are particularly sensitive to opsonization when compared with macrophages in other sites.20 This important function explains the increased risk of infections caused by encapsulated organisms that is seen after splenectomy and can lead to the devastating overwhelming postsplenectomy infection (OPSI). OPSI is a life-threatening complication seen in asplenic individuals that gained significant acceptance in 1953 after an observation by King and Shumacker.19,21 OPSI is encountered with greatest frequency within 2 years after splenectomy, in the very young, in those with other medical comorbidities, and in those with malignancies. Children, particularly those younger than 2 years of age, are at particularly high risk of OPSI because of their relatively immature immune system. The risk of postsplenectomy sepsis increases according to the specific indications for splenectomy; trauma, hematologic disorders, portal hypertension, Hodgkin disease, sickle cell disease, and thalassemia are associated with increasing cumulative incidence of sepsis.20 Overall, OPSI is estimated to occur in 0.9% to 3.2% of adults and 3.3% to 4.4% of children; the mortality rate is estimated to be between 0.8% and 1.3% in adults and 1.7% and 2.2% in children.22,23 OPSI occurs mostly in association with encapsulated organisms that require opsonization for effective phagocytosis. The most frequent of such pathogens are Neisseria meningitidis, Haemophilus influenzae type b, and Streptococcus pneumoniae. There are effective vaccines against all of them, and it is recommended that for adults they be administered ideally 2 weeks before an elective splenectomy to allow for an effective immune response. If this is not achievable because of need for urgent or emergent splenectomy, vaccinations should be administered after the operation. There are multiple guidelines, which vary slightly between countries. The current guidelines from the Centers for Disease Control and Prevention (CDC) are summarized in Table 136.2 and recommend administration of a second dose of vaccine against N. meningitidis and S. pneumoniae 8 weeks after initial vaccination.24,25 Daily prophylactic antibiotic use is not clinically proven to be beneficial and generally is not recommended.26,27 The exception to this rule may be the administration of prophylactic antibiotics in children under 2 years of age to prevent pneumococcal infection.28 Oral penicillin V or amoxicillin can be used. Other groups for whom prophylaxis might be considered include those high-risk postsplenectomy patients with thalassemias, Hodgkin disease, and immunodeficiencies.20 Even with vaccinations and other preventive measures, OPSI can occur, and early recognition is key to reduce morbidity and mortality. Asplenic or hyposplenic patients should be instructed to seek immediate medical attention at the first sign of illness, with some physicians advocating a personal supply of prescribed antibiotics to have on hand. With the onset of fever the patients should take the first dose of antibiotics and then seek immediate medical evaluation. Amoxicillinclavulanate or levofloxacin are appropriate choices for this purpose.26

1596

SECTION III  Pancreas, Biliary Tract, Liver, and Spleen

TABLE 136.1  Significant Cluster Designations (Markers) and Other Antigens: Description of Function and Clarification of Cell Type Typically Expressing the Antigen Cluster Designation

Function

Physiologic Staining

CD3 CD4

Antigen recognition T-cell activation

CD5 CD8

Signal transducer Increases avidity of cell-to-cell interactions Inactivates bioactive peptides

Thymocytes, peripheral T cells, NK cells Thymocytes, mature T cells (~65%, T-helper subset), macrophages, Langerhans cells, dendritic cells, granulocytes B cells of mantle zone of spleen and lymph nodes, almost all T cells Mature T cells (~35% of peripheral T cells, most cytotoxic T cells), NK cells, cortical thymocytes (70%–80%) Pre-B cells, cortical thymocytes; follicular center cells; granulocytes; lymphohematopoietic precursors; neutrophils Pre-B cells, B cells, first B-cell antigen after HLA-DR, follicular dendritic cells Most B cells (after CD19 and CD10 expression, before CD21/22 expression and surface immunoglobulin expression), retained on mature B cells until plasma cell development, follicular dendritic cells Activated mature B cells expressing IgM or IgD, monocytes/ macrophages, T-cell subsets, platelets, eosinophils, Langerhans cells, follicular dendritic cells All hematopoietic cells; stronger in lymphocytes (10% of surface area)

CD10 CD19

Regulates B-cell development, activation, differentiation Early activation of B cells

CD20

CD23

Regulates IgE synthesis; B-cell growth factor

CD45 CD79a

T- and B-cell antigen receptor– mediated activation Encodes Ig proteins

BCL2 BCL6

Induces apoptosis Regulates transcription

Early in B-cell differentiation (often positive when mature B-cell markers are negative), plasma cells Mantle zone B cells, germinal center centrocytes Germinal center centroblasts and centrocytes

HLA-DR, Human leukocyte antigen D-related; IgD, immunoglobulin D; IgM, immunoglobulin M; NK, natural killer.

TABLE 136.2  Centers for Disease Control and Prevention Recommended Vaccination Schedule for Planned Splenectomy*/ Asplenic Patients†24,25

Children

Adults (age 19 and older)

Pneumococcal Vaccination

Meningococcal Vaccination

Haemophilus Influenzae Type B Vaccination

Immunologically naïve 2–6 years‡: PCV13 followed by PCV 13 8 weeks later; PPSV23 8 weeks later; repeat PPSV23 at 5 years Immunologically naïve 6–18 years‡: PCV13 followed by PSV23 8 weeks later; repeat PPSV23 at 5 years Immunologically naïve‡: PCV13 followed by PPSV23 8 weeks later; repeat PPSV23 every 5 years

MenACWY series AND MenB series§

Hib once if 15 months or older and previously not vaccinated

MenACWY or MPSV4 2 months apart; repeat MenACWY every 5 years AND MenB series§ once

Hib once

*First vaccination should be administered at least 2 weeks before splenectomy if elective. † Even with vaccination, oral antibiotic prophylaxis with penicillin V or amoxicillin should be considered for children under 2 years of age, or high-risk postsplenectomy patients. ‡ For patients who have previously received any PCV or PPSV 23 or a combination of these vaccinations, the recommendations vary and are outlined in the CDC guidelines accessible online.24,25 § MenB-4C 2 doses 1 month apart or MenB-FHbp 3 doses, 1 each at 0, 2, and 6 months. Hib, H. influenzae type b; MenACWY, Meningococcal 4-valent conjugate; MPSV4, Meningococcal 4-valent polysaccharide; PCV13, Pneumococcal 13-valent conjugate; PPSV23, Pneumococcal 23-valent polysaccharide.

REFERENCES 1. Paraskevas GK, Koutsouflianiotis KN, Nitsa Z, Demesticha T, Skandalakis P. Knowledge of the anatomy and physiology of the spleen throughout Antiquity and the Early Middle Ages. Anat Sci Int. 2016; 91(1):43-55. 2. McClusky DA, Skandalakis LJ, Colborn GL, Skandalakis JE. Tribute to a triad: history of splenic anatomy, physiology, and surgery—part 1. World J Surg. 1999;23(3):311-325. 3. McClusky DA, Skandalakis LJ, Colborn GL, Skandalakis JE. Tribute to a triad: history of splenic anatomy, physiology, and surgery—part 2. World J Surg. 1999;23(5):514-526.

4. Delaitre B, Maignien B. Laparoscopic splenectomy—technical aspects. Surg Endosc. 1992;6(6):305-308. 5. Paraskevas F. Lymphocytes and lymphatic organs. In: Greer JP, ed. Wintrobe’s Clinical Hematology. 13th ed. Philadelphia: Wolters Kluwer Health/Lippincott Wiliams & Wilkins; 2014. 6. Mebius RE, Kraal G. Structure and function of the spleen. Nat Rev Immunol. 2005;5(8):606-616. 7. Hörnblad A, Eriksson AU, Sock E, Hill RE, Ahlgren U. Impaired spleen formation perturbs morphogenesis of the gastric lobe of the pancreas. PLoS One. 2011;6(6):e21753. 8. Park S, Hong SM, Ahn IS. Can splenocytes enhance pancreatic beta-cell function and mass in 90% pancreatectomized rats fed a high fat diet? Life Sci. 2009;84(11-12):358-363.

Anatomy and Physiology of the Spleen  CHAPTER 136  9. Wu S-C, Fu C-Y, Muo C-H, Chang Y-J. Splenectomy in trauma patients is associated with an increased risk of postoperative type II diabetes: a nationwide population-based study. Am J Surg. 2014;208(5):811816. 10. Dieguez-Acuna FJ, Gygi SP, Davis M, Faustman DL. Splenectomy: a new treatment option for ALL tumors expressing Hox-11 and a means to test the stem cell hypothesis of cancer in humans. Leukemia. 2007;21(10):2192-2194. 11. Asayesh A, Sharpe J, Watson RP, et al. Spleen versus pancreas: strict control of organ interrelationship revealed by analyses of Bapx1−/− mice. Genes Dev. 2006;20(16):2208-2213. 12. Fraker D. The spleen. In: Greenfield LJ, Mulholland MW, eds. Greenfield’s Surgery: Scientific Principles and Practice. 5th ed. Philadelphia: Wolters Kluwer Health/Lippincott Wiliams & Wilkins; 2010. 13. Tavakkoli A. The spleen. In: Zinner MJ, Ashley SW, eds. Maingot’s Abdominal Operations. 12th ed. New York: McGraw Hill Medical; 2013. 14. Saber AA, Helbling B, Khaghany K, Nirmit G, Pimental R, McLeod MK. Safety zone for splenic hilar control during splenectomy: a computed tomography scan mapping of the tail of the pancreas in relation to the splenic hilum. Am Surg. 2007;73(9):890-894. 15. Koshenkov VP, Pahuja AK, Németh ZH, Abkin A, Carter MS. Identification of accessory spleens during laparoscopic splenectomy is superior to preoperative computed tomography for detection of accessory spleens. JSLS. 2012;16(3):387-391. 16. Bergeron E, Ratte S, Jeannotte S, Recoskie MJ. The use of a handheld gamma probe for identifying two accessory spleens in difficult locations in the same patient. Ann Nucl Med. 2008;22(4):331-333. 17. Poulin EC, Thibault C. The anatomical basis for laparoscopic splenectomy. Can J Surg. 1993;36(5):484-488.

1597

18. Klimpel V. [Does Kehr’s sign derive from Hans Kehr? A critical commentary on its documentation?]. Chirurg. 2004;75(1):80-83. 19. Porembka MR, Doyle M, Chapman WC. Disorders of the spleen. In: Greer JP, ed. Wintrobe’s Clinical Hematology. 13th ed. Philadelphia: Wolters Kluwer Health/Lippincott Wiliams & Wilkins; 2014. 20. Connell NT, Shurin SB, Schiffman FJ. The spleen and its disorders. In: Hoffman R, Benz EJ Jr, Silberstein LE, et al., eds. Hematology: Basic Principles and Practice. 6th ed. Philadelphia: Elsevier; 2013. 21. Sinwar PD. Overwhelming post splenectomy infection syndrome— review study. Int J Surg. 2014;12(12):1314-1316. 22. Holdsworth RJ, Irving AD, Cuschieri A. Postsplenectomy sepsis and its mortality rate: actual versus perceived risks. Br J Surg. 1991;78(9):1031-1038. 23. Bisharat N, Omari H, Lavi I, Raz R. Risk of infection and death among post-splenectomy patients. J Infect. 2001;43(3):182-186. 24. Birth-18 Years Immunization Schedule. CDC [Internet]. http:// www.cdc.gov/vaccines/schedules/hcp/imz/child-adolescent.html; 2016. Accessed 7 November 2016. 25. Adult Immunization Schedule by Medical and Other Indications. CDC [Internet]. http://www.cdc.gov/vaccines/schedules/hcp/ adult.html; 2016. Accessed 21 April 2016. 26. Makris M, Greaves M, Winfield DA, Preston FE, Lilleyman JS. Long-term management after splenectomy. Lifelong penicillin unproved in trials. BMJ. 1994;308(6921):131-132. 27. Harji DP, Jaunoo SS, Mistry P, Nesargikar PN. Immunoprophylaxis in asplenic patients. Int J Surg. 2009;7(5):421-423. 28. Prevention of Pneumococcal Disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP) [Internet]. https://www.cdc.gov/mmwr/preview/mmwrhtml/00047135.htm. 2016. Accessed 7 November 2016.