Physiology, Spleen


Article Author:
Vaishali Kapila


Article Editor:
Faiz Tuma


Editors In Chief:
Jasleen Jhajj
Cliff Caudill
Evan Kaufman


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
12/30/2018 1:01:50 AM

Introduction

The spleen is a significant organ of the hematologic and reticuloendothelial systems. It is an intraperitoneal organ located in the left upper quadrant of the abdomen posterior and lateral to the stomach.[1]

Cellular

The spleen contains 2 major units: red pulp and white pulp.[2] The white pulp is lymphatic tissue located around a central arteriole and contains mainly white blood cells that can initiate the adaptive immune response. This tissue is organized so the germinal center, innermost area, contains B-cells and the surrounding marginal zone contains T-cells.[3] Moreover, the marginal zone is surrounded by a periarteriolar lymphoid sheath (PALS), which contains T-cells. White pulp throughout the spleen is surrounded by red pulp. Red pulp is composed of splenic cords (Cords of Billroth) and a large volume of venous sinuses, which gives the structure a red appearance histologically. Splenic cords provide the organ structure through reticulin and fibrils as well as a reservoir of monocytes to aid in wound healing. Splenic cords lead to blood sinuses where macrophages respond to antigens and filter abnormal or aging erythrocytes out of blood flow.[4]

A thin, fibrous capsule covers the spleen from which trabeculae arise. Trabeculae are fibrous bands transporting blood vessels to and from the splenic pulp.[5]

Development

The spleen is derived from a mass of mesenchymal cells in the dorsal mesogastrium, later known as the greater omentum.[6] Vasculature of the primordial spleen begins to develop in the fifth week when hematogenesis (blood cell formation) first develops along the aorta and parts of the mesenchyme. When the fetal period begins in week 9, erythropoiesis functions mainly in the liver and partially in the spleen. By the end of week 12, the spleen is taking a larger role in erythropoiesis as the major site of activity until week 28 when the bone marrow becomes the primary site. In a normal adult, the spleen is located intraperitoneally in the left upper abdominal quadrant near the tail of the pancreas and above the splenic flexure.[7] The spleen is supplied by blood from the splenic artery (branching off of the celiac trunk) and drained by the splenic vein (uniting with the superior mesenteric vein to form the hepatic portal vein).[6]

Function

In utero, the spleen is responsible, in part, for hemoglobin synthesis around the 10th through 25th week of pregnancy. After birth, the primary function of the spleen shifts to the following major roles: 

  • Filtration 
  • Iron metabolism
  • Prevention of infection
  • Red blood cell and platelet storage

Filtration of erythrocytes and platelets are performed via splenic cords in the red pulp. Young, flexible red blood cells pass through the epithelial cells of the splenic cords and continue through blood flow. On the other hand, older, larger, and deformed red blood cells are trapped by the splenic cords and phagocytosed by macrophages waiting on the reticulum and sinus endothelium.[8]

Furthermore, splenic macrophages in red pulp are specialized to recycle iron from the breakdown of senescent and damaged red blood cells.[9] Macrophages can either store ingested iron in the cytoplasm or export it via ferritin into the bloodstream.[10] 

Not only does the spleen play a role in the breakdown of red blood cells, but it can also play a role in hematopoiesis. While not a typical function, in pathologic conditions, such as beta thalassemia major, extramedullary hematopoiesis may occur to help the bone marrow compensate for the hemolysis taking place.

Infection is prevented by 2 major mechanisms: phagocytic filtration of the bloodstream and production of opsonizing antibodies. As mentioned above, macrophages supervise the flow of red blood cells, platelets, as well as microorganisms through the splenic cords.[11] Additionally, in the follicle of the white pulp, infectious antigens and blood-borne pathogens are presented by antigen presenting cells.[12] This initiates activation of T-cells and B-cells which eventually leads to the production of opsonizing antibodies.[13] After opsonization, macrophages, dendritic cells, and neutrophils phagocytose the antigen.[14] Opsonization is important to clear particular microorganisms like encapsulated bacteria and intra-erythrocytic parasites.[15] The spleen is the largest secondary lymphoid organ in an adult human.[16]

As a reservoir for blood, the spleen weights about 100 g. The organ can respond to sympathetic stimulation by contracting its fibroelastic capsule and trabeculae to increase systemic blood supply. In particular, this important function is observed during hemorrhage. About 25% to 30% of red blood cells (RBCs) are stored in the spleen, and about 25% of platelets are normally sequestered in the spleen.

Related Testing

While not highly sensitive or specific, a physical exam can be performed to test for splenomegaly. Laboratory work that can help assess splenic activity is a complete blood count (CBC) complimented by a peripheral blood smear. Abnormalities in quantity or quality of cell types can provide evidence of pathology involving the spleen. In addition to the physical exam and laboratory testing, there is a variety of imaging modalities to visualize the spleen.[17]

A focused assessment with sonography in trauma (FAST) exam is performed using ultrasound to assess for the presence of fluid where it should not be in trauma evaluation. A FAST exam looks at 4 windows: pericardial window, Morrison’s pouch (right upper quadrant between liver and right kidney), left upper quadrant (between spleen and left kidney), and the suprapubic region to look at the bladder and pelvis. The exam is considered positive with fluid in any of these spaces and combination with hemodynamic instability is an indication for exploratory laparotomy. With positive fluid in the pericardial window, a pericardiocentesis can be performed.[18]

Computed tomography (CT) and magnetic resonance imaging (MRI) are beneficial tools to visualize and characterize the spleen. Both can be used to measure the spleen and identify physical abnormalities of the spleen. While not necessary, use of contrast can aid in tracing blood flow and help identify any leaks or pathologic fluid collection.[19]

Biopsy of the spleen is rarely completed secondary to concerns of a risk of bleeding. More often, a blood marrow biopsy is completed to evaluate blood cells for cancer.[19]

Pathophysiology

Extravascular Hemolysis 

Hemolysis of red blood cells can be classified as intravascular or extravascular. As the name implies, intravascular hemolysis is defined as the breakdown of red blood cells in vessels. Extravascular hemolysis is defined as the breakdown of red blood cells in the reticuloendothelial system, such as the spleen and liver. In extravascular hemolysis, it is the macrophages that perform the hemolysis. Patients with extravascular hemolysis present with splenomegaly due to work hypertrophy of the spleen and jaundice due to the increased levels of unconjugated bilirubin from broken down blood cells. Laboratory results can reveal anemia, unconjugated hyperbilirubinemia, and an increased reticulocyte count, which reflects a good bone marrow response to the anemia. Because of the increased bilirubin, patients with extravascular hemolysis are at an increased risk of bilirubin gallstones, which can lead to biliary pathology. Conditions that can cause extravascular hemolysis include sickle cell disease, hereditary spherocytosis, hemoglobin C, malaria, IgG immune hemolytic anemia, and beta thalassemia major. Treatment is typically geared toward the underlying cause, with splenectomy providing a cure in some cases.[20][21][22]

Splenomegaly 

Splenomegaly is the abnormal enlargement of the spleen with a length greater than 10 cm. This irregularity can be caused by multiple types of mechanisms: hypertrophy, infiltration, congestion, myeloproliferative, and neoplastic. RBC work hypertrophy suggests increased normal splenic function by filtering large amounts of abnormal erythrocytes from the circulation. Examples of this type include hereditary spherocytosis and sickle cell anemia.

Meanwhile, immune response work hypertrophy from chronic systemic infections or immune-mediated disorders can also cause splenomegaly. Malignant, benign, or metabolic conditions infiltrate the spleen in cases like sarcoidosis and some neoplasms leading to splenomegaly.  Congestive splenomegaly secondary to obstruction of blood flow and, therefore, engorged with blood in the red pulp. Myeloproliferative disorders include chronic myeloid metaplasia. Neoplastic origins include chronic lymphocytic leukemia and lymphoma.[23]

Palpation by percussion is performed to evaluate for an enlarged spleen. This physical exam is not diagnostic of the disease. Diagnosis is more precisely measured by imaging studies like CT, MRI, or US. However, if splenomegaly is evaluated, it may be idiopathic or secondary to an underlying disease.[24]

Hyposplenia/Post-Splenectomy/Asplenia Immunization and Antibiotic prophylaxis 

There are a variety of causes for splenic dysfunction ranging from extravascular hemolysis to sickle cell disease and trauma. Due to the spleen playing a large role in the immune system, recognizing splenic dysfunction or preparing to lose the spleen is critical in preventing death secondary to asplenic sepsis. For any patient with splenic dysfunction, they must receive prophylactic vaccination against encapsulated organisms, such as Streptococcus pneumoniae, Neisseria meningitides, and Haemophilus influenzae. Due to the increased risk of a Streptococcus pneumoniae infection following infection from the influenza virus, hyposplenic patients should receive yearly influenza vaccinations as well. Because vaccinations do not cover all serotypes of the organism being vaccinated against, many patients receive either daily prophylactic antibiotics, usually penicillin, or an emergency supply should they develop a fever. The timing at which these practices are implemented depends on the reason for splenic dysfunction. In patients with functional asplenia or hyposplenia, such as in sickle cell disease, prophylaxis should begin as soon as possible. In cases of elective spleen surgery, prophylaxis should begin two weeks before surgery. In emergency surgery, prophylaxis should begin two weeks after surgery.[25]

Portal Hypertension 

Portal hypertension is a result of increased pressure in the portal venous system which drains the stomach, intestine, spleen, and pancreas. As portal hypertension worsens, the venous congestion of the splenic vein can cause splenomegaly. The spleen undergoes hyperplasia and fibrosis, which further increases the blood supply to the spleen, exacerbating the condition. With this hyperplasia, there has been evidence that the white pulp increases in size, possibly indicating an alteration in immune system function. Sometimes, a splenorenal shunt is performed to help reduce the burden of portal hypertension by reducing the contribution of blood by the splenic vein.[26][27]

Clinical Significance

Immune Thrombocytopenic Purpura (ITP) 

ITP is thought to be an autoimmune condition resulting in thrombocytopenia, petechiae/purpura, and bleeding from mucosal surfaces. There have been many antibodies implicated in the pathogenesis of ITP with the 2 main autoantibodies being against IgG and the glycoprotein (GP) IIb/IIIa complex on platelets. Platelets tagged by these autoantibodies then get broken down by phagocytes in the spleen, resulting in thrombocytopenia. Without platelets to form the platelet plug, which is the first step of hemostasis, the patient becomes more susceptible to bleeding. Most patients with ITP only have minor bleeds, such as nosebleeds or conjunctival bleeds. However, these patients are at risk for serious bleeds, and that risk helps guide management. ITP tends to affect children around 5 years old or older adults. In children, ITP typically presents with sudden onset usually following a microbial illness and is brief. In adults, it typically presents with insidious onset and is a chronic condition. In both patient populations, there must be a high index of suspicion and ITP is usually a diagnosis of exclusion. A CBC and peripheral blood smear are typically performed in the initial evaluation. In adults, it is important to rule out ITP secondary to other autoimmune diseases, so an anti-nuclear antibody (ANA) and autoantibodies specific for other conditions may be tested as well. A more specific test for ITP would be autoantibodies against IgG and GP IIb/IIIa. In children, treatment is generally conservative as ITP is generally transient. Adults typically require treatment. Prednisone is the first-line treatment in adults and can also be used to treat children. IVIG can also be used to reduce or eliminate causative autoantibodies and is typically used before steroids in children and after steroids in adults. In cases refractory to medical management, splenectomy can be performed as most platelet breakdown occurs there.[28]

Trauma 

The spleen is one of the most commonly injured organs in blunt abdominal trauma. While it is sometimes injured in penetrating trauma, this is less common. Like with other traumatic injuries, the primary focus taking care of a trauma patient is resuscitation and rapid detection of serious injuries following the advanced trauma life support (ATLS) protocol. After a thorough physical exam and fluid resuscitation have been performed, a FAST exam is typically performed early in the evaluation of a trauma patient, sometimes as a part of the physical exam. Because FAST exam can sometimes miss intraparenchymal injuries, a high degree of suspicion must be used. The rest of the workup is largely dependent on hemodynamic stability. If the patient is hemodynamically stable, regardless of FAST exam results, the patient should undergo imaging using CT scan. Active extravasation and blush of contrast are indicative of active bleeding. If the patient is hemodynamically unstable with a positive FAST exam, the patient can undergo exploratory laparotomy without further workup.

Splenic injury in trauma is generally classified into five grades according to the American Association for the Surgery of Trauma (AAST), which typically describe the injuries as lacerations, hematoma, or vascular and describe the extent of injury to vessels or specific splenic tissue. Injury grades I-III are most commonly treated in the hospital using medical management. Surgical management can be pursued if the patient’s condition does not improve or respond to medical management. Injuries greater than grade III are considered high-grade and typically treated using surgery, although select cases are managed medically. Procedural treatment of splenic injury can range from the relatively non-invasive angioembolization to partial or total splenectomy. Medical management generally consists of symptomatic treatment with serial CBCs to trend the hemoglobin. Serial imaging can be performed if there is suspicion for bleeding, such as decreasing hemoglobin, or signs of peritonitis. A bleed may present later as a hematoma, the spleen itself, or another collection of fluid may have ruptured between initial survey and admission.[29][30]


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Physiology, Spleen - Questions

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What percentage of red blood cells are stored in the spleen?



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A 45-year-old male with a history of anemia is brought to his primary care provider's clinic for diffuse abdominal pain. The physician palpates the abdomen and notes significant enlargement of the left upper quadrant with a dull tone during percussion. Most likely, the patient's physical exam can be explained by abnormalities in what part of the spleen?



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A 55-year-old female is brought to the emergency department due to blunt abdominal trauma. The patient is resuscitated and, then, a FAST exam is performed. Injury is noted to the spleen. What function is not affected by the spleen in this patient?



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Physiology, Spleen - References

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