Spleen

Anatomy and Function

The spleen lies along the left body wall within the superficial leaf of the greater omentum and is attached to the greater curvature of the stomach by the omentum, more specifically, the gastrosplenic ligament [1]. Although its shape, size, and position vary with species and breed as well as other factors such as drugs or pathologic conditions, the spleen is typically oblong and red-blue. Blood enters the spleen from the splenic artery, a branch of the celiac artery, and leaves through the splenic vein, which empties into the gastrosplenic vein and eventually into the portal vein [1]. Splenosis or accessory splenic nodules are commonly found within the omentum of small animals and likely represent small revascularized fragments of spleen that occur secondary to trauma [1-4]. Single nodules of ectopic splenic tissue embedded along the surface of the pancreas are described in cats but are not attributed to trauma.4 Siderotic or siderofibrotic plaques are slightly raised, yellow to grey, irregularly sized deposits of calcium and iron that are commonly found along the margin of the splenic capsule of older dogs [5]. These plaques are thought to develop secondary to splenic trauma [6,7]. The spleen of dogs and cats is often visible radiographically. On the ventrodorsal view, the head of the spleen sits laterally on the left side and is often visualized as a triangular soft-tissue density just caudal to the gastric fundus and cranial to the left kidney. On a lateral radiographic projection, the tail of the spleen can be identified along the ventral body wall just caudal to the liver.

The spleen is composed of a capsule rich in elastic and smooth muscle fibers, a network of fibromuscular trabeculae, and the parenchyma, which is located between the capsule and trabeculae and consists of red and white splenic pulp [1]. The white pulp contains diffuse and nodular lymphoreticular tissue and the red pulp is primarily made of venous sinuses and cords of reticular cells [1]. Whereas the canine spleen is considered sinusoidal, the feline spleen has a poorly developed sinusoid system and is often referred to as nonsinusoidal. As whole blood filters through the trabecular meshwork of the spleen, plasma is skimmed off into the white pulp while red blood cells move toward the red pulp [8]. In dogs, a small portion of the blood that enters the spleen is delivered directly into the venous sinuses of the red pulp, bypassing the splenic cords and travelling rapidly through the spleen; this is known as a closed circulation. A larger portion of the blood that enters the spleen empties into the red pulp and circulates slowly through the fine trabecular meshwork of the splenic cords; this is known as the open circulation. Within the cords, red blood cells distort themselves to squeeze through small pores between the reticuloendothelial cells lining the sinus walls to be released into the venous circulation. This process slows the flow of red blood cells through the spleen and results in increased blood viscosity, low blood pH, and decreased blood concentrations of glucose and oxygen. These conditions cause increased mechanical and metabolic stress to older or damaged red blood cells. During their slow passage through the red pulp of the spleen, abnormal red blood cells, therefore, are culled or pitted as required and bacteria or unwanted debris are phagocytosed by the macrophages that line the trabeculae and venous sinuses.

Physiology – Normal Splenic Functions

Red Blood Cell Storage

The slow passage of red blood cells from the splenic cords to the splenic sinuses essentially traps red blood cells within the trabeculae and makes the red pulp of the spleen a reservoir for red cells. It has been shown that 10 to 20% of a dog’s red blood cells may be sequestered in the spleen at any one time.9 Smooth muscle fibers of the spleen contract in response to endogenous or exogenous catecholamines in order to rapidly release the stored red blood cells into the general circulation [9]. In fact, blood loss equal to 40% of the circulatory volume is fatal in splenectomized dogs.10 In addition, approximately 30% of circulating platelets can be found within the normal spleen at any given time [9,11].

Hematopoiesis

Although the spleen actively participates in red blood cell production during fetal development, hematopoeisis within the spleen stops at birth when the bone marrow takes over this task almost exclusively. In times of high demand, when the bone marrow is unable to produce enough red blood cells, foci of extramedullary hematopoiesis can develop within the spleen [11,12]. These foci are thought to be derived from pluripotent hematopoeitic stem cells present within the spleen. Extramedullary hematopoeisis is a common cytologic and histologic diagnosis in dogs and cats [3,13].

Red Blood Cell Maturation

Reticulocytes released into circulation by the bone marrow become trapped within the spleen where they spend a few days in order to complete their maturation. While in the spleen, remaining intracellular material and excessive cell membrane are removed. By this process, immature cells entering the spleen leave as mature, biconcave cells [8].

Removal of Abnormal or Senescent Red Blood Cells

Red blood cells live approximatly 4 months, after which time they are no longer pliable enough to squeeze through the pores of the splenic sinuses. Older red blood cells either rupture as they attempt to pass through sinus pores or they simply become trapped within the spleen and are removed by the reticuloendothelial system; this is also known as culling [8]. During phagocytosis, the iron present in the red cells is recycled and released into circulation as plasma transferrin to be used by the bone marrow to produce new erythrocytes, or it is retained in the spleen and stored by the phagocyte as ferritin and hemosiderin [14]. Whereas normal red blood cells deform to pass through the fenestrations in the splenic sinuses, the passage of more rigid cells containing inclusion bodies is delayed. The increased contact time with the perisinusoidal phagocytic cells allows removal of inclusion bodies such as Heinz bodies and Howell-Jolly bodies; this process is known as pitting [8].

Immune Function

Because of its architecture and sluggish blood flow, the spleen provides an excellent environment for phagocytosis and immune function. For this reason, the spleen is more effective at removing poorly opsonized bacteria than is the liver [11]. The pulp of the spleen contains large reticuloendothelial cells that phagocytose circulating debris, microorganisms (bacteria and parasites), and antibody-coated cells. Removal of antibodies that coat the red blood cell surface (pitting) results in the formation of a smaller cell, a spherocyte. Because spherocytes are less pliable, they tend to get trapped within the spleen and are destroyed by phagocytosis [8]. The spleen is also thought to play a role in the complement pathways and in the the production of B and T lymphocytes, plasma cells, and antibodies (especially IgM) [8].

Other Functions

Other reported functions include the production of the tetrapeptide tuftsin, a potent stimulator of neutrophil and macrophage phagocytic activity in man; storage and activation of Factor VIII; regulation of the formation and degradation of angiotensin-converting enzyme; and modulation of plasma norepinephrine levels and/or prostaglandin E2 activity [8].

Diseases of the Spleen

Dogs and cats with splenic diseases have clinical signs and hematobiochemical changes that vary considerably depending on the underlying pathology [15,16]. Ventricular tachyarrhythmias are prevalent in dogs with splenic masses, particularly if the mass has ruptured [17,18]. Arrhythmias have also been described in dogs with splenic torsion [19,20] and have been commonly reported during and after splenectomy [16,20]. The mechanism of arrhythmias secondary to splenic disease is not well understood but may result from transient ischemic coronary episodes, shock, reduced cardiac output, acidosis, or toxemia [20].

A study evaluating hematologic parameters in dogs with malignant and benign splenic lesions revealed that dogs with sarcomas have significantly higher total white blood cell counts compared with dogs with benign disease, and significantly higher neutrophil counts than do dogs with round cell tumors or benign disease [21]. Dogs with round cell tumors have significantly lower platelet counts than do dogs with benign disease and lower monocyte counts than do dogs with sarcomas or benign disease [21]. Although the degree of anemia and presence of schistocytes was not shown to vary with the disease process in one study [21], another reported that anemia, nucleated red blood cells and abnormal cell morphology were associated with splenic neoplasia [22].

Treatment for most splenic disorders (splenic abscess, torsion, neoplasia, and trauma) involves splenectomy. Splenectomy is also indicated when medical management of immune-mediated diseases (immune-mediated hemolytic anemia [IMHA] and immune-mediated thrombocytopenia) has failed and for the detection of occult carriers of Ehrlichia, Babesia, or Hemobartonella in blood donors [23]. The effects of splenectomy are not completely understood but it is generally accepted that the spleen is not essential to life in dogs and cats. Following splenectomy, the functions of the spleen are carried out by the liver, lymph nodes, and bone marrow. However, since the spleen takes over hematopoeisis when the bone marrow is unable to do so, splenectomy is contraindicated in cases of bone marrow hypoplasia.

A study evaluating hematologic and biochemical changes at 3 and 10 days post splenectomy in dogs with splenic disease revealed no consistent changes in RBC, WBC, and platelet counts, or bone marrow samples or biochemical profiles.16 Although not significant, thrombocytosis (platelet count greater than 500,000/μl) was reported in 50% of patients 10 days after surgery [16]. Serum iron, transferrin, and IgM concentrations also remained normal after splenectomy [16]. These findings differ slightly from those previously reported for normal dogs, which included significant increases in platelet counts, minimal elevation in WBC count, and reduction in hematocrit, red cell volume, plasma volume, and iron turnover [24]. The exact cause for postsplenectomy thrombocytosis is unknown but it has been reported to resolve after 40 days in normal dogs [25]. Although postsplenectomy sepsis is commonly reported in people [8,26], and a few cases have been reported in small animals [9,27], this does not appear to be a common complication. A study reports that approximately 20% of patients undergoing splenectomy developed pyrexia in the postoperative period, but no correlation was found between pyrexia and positive bacterial culture of the splenic tissue [16].

Because the spleen is no longer present to filter the blood, red blood cell inclusions such as Howell-Jolly bodies are more commonly seen and small animal patients are at higher risk for developing parasitic blood infections [28,29]. Other reported consequences of splenectomy include decreased exercise tolerance and response to shock or hemorrhage [30,31]. Retrospective evaluations of patients undergoing splenectomy for various conditions have identified no complications related to the procedure itself or to asplenism [15].

Prevalence of Splenic Diseases

Significant discrepancy exists with regard to the incidence of neoplastic versus nonneoplastic splenic lesions in dogs and cats. Some studies report that benign splenic masses such as hematoma and nodular hyperplasia are most commonly diagnosed in dogs undergoing splenectomy [3,9,15,32], whereas others describe neoplastic lesions, especially hemangiosarcoma as being most common [22,33,34]. Neoplastic splenic pathology, especially mastocytosis, is reported most commonly in cats [4].

Splenomegaly

Splenomegaly is the term used to describe a uniformly enlarged spleen regardless of the cause. Splenic mass is the terminology used when an asymmetric enlargement of the spleen is noted. Dogs appear to develop splenic masses more commonly than diffuse splenic enlargement, whereas cats most commonly develop diffuse splenomegaly [3,4,22].

Drug-induced splenomegaly is reported with the administration of phenothiazine barbiturates such as acepromazine and ultra-short-acting barbiturates such as thiopental [35]. These drugs result in significant pooling of blood within the spleen secondary to smooth muscle relaxation of the splenic capsule [9]. In fact, as much as 5 to 40% of a dog’s red blood cells may become sequestered in the spleen during anesthesia [36,37]. One study revealed that induction protocols containing thiopental and a combination of ketamine-diazepam caused significant splenic enlargement compared with induction protocols that used propofol [38]. Drug-induced splenomegaly has been shown to last more than 2 hours [35,38]. Other causes of congestive splenomegaly include portal hypertension, right-sided heart failure, and splenic torsion [30].

Splenic Torsion

Splenic torsion is a rare condition that affects large, deep chested dogs and may occur as a primary entity or secondary to gastric dilation volvulus (GDV) [19,20]. Great Danes and German shepherd dogs have been identified as breeds that are predisposed to splenic torsion; males are affected more frequently than females [19]. Although the etiology of spontaneous splenic torsion is uncertain, it has been suggested that the spleen retains a rotated position after spontaneous resolution of a GDV or that repeated gastric dilation stretches the gastrosplenic ligament, making the spleen more prone to torsion [39,40]. Torsion of the splenic vascular pedicle and obstruction of the venous outflow causes blood to accumulate in the sinusoids, eventually leading to thrombosis of splenic vessels. Clinical signs vary, depending on whether the torsion is acute or chronic, and include shock and abdominal pain in acute cases and anorexia, lethargy, vomiting, discolored urine, and polyuria/polydypsia in chronic cases [19,20]. A diagnosis of splenic enlargement is usually made by palpation and radiography [19,41]. Specific radiographic (C-shaped spleen) and ultrasonographic (generalized splenomegaly, hypoechoic pattern consistent with congestion and abnormal flow through the hilar splenic vessels) abnormalities have also been reported [19,40-42]. Splenectomy is the treatment of choice. Most surgeons recommend removal of the spleen without derotating the pedicle to prevent the release of thrombi, endotoxins, and free radicals [19,20,43], although one report describes an acute case in which the pedicle was derotated in order to salvage the spleen of a racing greyhound [44]. A previous case report described a 180-degree splenic torsion that was initially untwisted but required complete splenectomy four days later owing to complete torsion of the splenic pedicle [20]. Montgomery suggested that splenopexy should be performed if the surgeon elects to preserve the spleen but a technique was not described [45]. Gastropexy is recommended following splenectomy for splenic torsion, to decrease the risk of gastric torsion in the future [19,46]. Although the prognosis is not always good, one study reported 100% survival in 19 cases of splenic torsion [19].

Splenic Hyperplasia

Splenic hyperplasia represents a more physiologic form of diffuse splenic enlargement that typically remains asymptomatic. Hyperplasia can occur owing to immune stimulation, secondary to infection or septicemia (splenitis), or with splenic hyperactivity related to the active removal of abnormal red blood cells in patients with IMHA or blood parasites. Passive congestion secondary to portal hypertension caused by hepatic disease or right-sided heart failure are other potential causes. Nodular hyperplasia is common in older dogs and is characterized by single or multiple subcapsular nodules of various size. Nodular hyperplasia is of no clinical significance but must be differentiated from other less benign splenic masses.

Splenic Hematoma

Splenic hematoma can develop secondary to an underlying splenic pathology such as neoplasia, secondary to trauma, or as a spontaneous lesion [5,34,47]. An association has been made between splenic hematomas and nodular hyperplasia in the dog. Nodular hyperplasia results in distortion of the marginal splenic blood flow, causing an accumulation of blood within and around the hyperplastic nodules leading to the formation of a hematoma [3]. Splenic hematomas can present as multiple smaller masses or as a single mass that might be as large as 20 cm in diameter [33]. Splenic hematomas cannot be grossly differentiated from hemangiosarcomas but are often larger, firmer, and more organized than hemangiosarcoma lesions [3]. Splenic hematoma is treated by splenectomy and appears to have a good prognosis, with one study reporting that all dogs died of unrelated disease at a median of 14 months postsplenectomy [47]. A more recent study reported 83% and 64% survival rates at 2 and 12 months, respectively [32].

Splenic Neoplasia

Infiltrative neoplastic diseases such as lymphoma, histiocytosis, and mastocytosis are common causes of splenomegaly [48,49]. Malignant histiocytosis is most commonly reported in Bernese Mountain dogs [49]. Mast cell neoplasia is most frequent in cats and represents the number one splenic condition diagnosed in this species [4]. Hemangioma and its malignant counterpart hemangiosarcoma (HSA) are tumours of endothelial origin that occur commonly in dogs and less commonly in cats.3,4 Hemangiosarcoma has been reported by some as the most common splenic mass diagnosed in dogs [22,33,34], but others have reported higher rates for benign lesions such as hemangioma, hematoma, and nodular hyperplasia [3,9,15,32]. Other neoplastic disorders such as leiomyoma, leiomyosarcoma, fibrosarcoma, lipoma, and liposarcoma as well as other sarcomas are associated with asymmetric splenic enlargement, resulting in a mass effect but these occur less frequently [33,34,50,51].

Hemangiosarcoma has been described as the most common splenic tumor in dogs [3,15,33,34]. The heart, skin, and liver are other common sites of primary HSA [52,53]. Male, large breed dogs, particularly German shepherd dogs, Labrador and golden retrievers are predisposed to HSA [3,15,22,34,52]. Splenic HSA can present as single or multiple masses of variable diameter; these masses can rupture and develop omental attachments [33]. Gross distinction between HSA and splenic hematoma is not possible, although splenic HSA tends to be multifocal with nodules that are individually smaller and more cavitated than those seen in cases of hematoma.3 Metastasis to the liver is most common, followed by the omentum and mesentery [33,52,53]; more than 50% of patients have metastatic lesions at the time of diagnosis [52]. Other commonly reported sites of metastasis include the kidney, regional lymph nodes, heart, and lungs [33,52,53]. When metastasis is not present, splenectomy is the treatment of choice. Lesions of nodular hyperplasia within the liver can easily be confused with metastasis; as such, hepatic nodules should be biopsied to confirm the diagnosis [54]. Partial splenectomy is not recommended even in cases where a localized mass is present.

Histologic differentiation between hematoma, hemangioma, and HSA can be difficult; multiple tissue sections should be examined to reduce the risk of misdiagnosis [3,55]. The interval between diagnosis and death is generally short (3 to 4 months) and does not appear to be affected by the stage of disease (presence or not of visible metastasis) [22,33,52,54]. A large retrospective study reported 31% and 7% survival rates at 2 and 12 months, respectively [32]. In this last study, the presence of a single mass was associated with an increased survival rate (16%) at 12 months.32 Newer chemotherapeutic protocols may hold promise in improving survival [56].

Splenic Trauma

Splenic trauma is most commonly related to blunt abdominal trauma. Trauma commonly results in rupture of the splenic capsule and parenchyma, leading to abdominal hemorrhage. Iatrogenic trauma to the spleen is also possible during abdominal procedures and laparoscopy. Owing to its highly vascular nature, trauma to the spleen can lead to significant abdominal hemorrhage and possibly death. Surgical intervention may be required in cases where conservative treatment (abdominal pressure bandage, intravenous fluids, and blood transfusions) is not successful at controlling hemorrhage. Surgical treatment should aim to control hemorrhage and, if possible, to save the spleen. Hemostasis may be achieved by suturing the ruptured splenic parenchyma and capsule with mattress sutures and applying an omental patch or a hemostatic sponge such as Surgicel or Gelfoam to control residual oozing [57-59]. As in humans, if splenectomy is required, partial splenectomy is preferred in order to retain some splenic function [59-60]. Autotransplantation of resected splenic tissue in an attempt to maintain some splenic function has been studied in dogs as a model for human trauma patients [60-62]. Techniques described include the implantation of avascular "splenic chips" or slices within a pouch of the greater omentum; conflicting results regarding the success of this technique have been reported [60-62]. Although autogenous splenic transplants have been shown to grow and hypertrophy in dogs, the amount of splenic tissue required for normal function is unknown.

Splenic Abscess

Splenic abscessation is rarely reported but can occur as a single abscess [15,33] or as diffuse microabscesses spread throughout the entire organ [4,33,34]. Abscesses have been described secondary to sepsis (bacteremia) and penetrating foreign bodies [4,33,63]. Single splenic abscesses can be removed by partial [15] or complete splenectomy [33]. Diffuse abscessation is best treated by complete splenectomy [33,34].

Splenic Thrombosis and Infarction

Splenic infarction is a condition that is most commonly associated with a coagulopathy and splenomegaly as well as other systemic disorders such as cardiac, liver, or renal disease, neoplasia, hyperadrenocorticism, sepsis, and DIC [3,4,33,42. Splenic infarcts can have a nodular appearance that make them difficult to differentiate from nodular hyperplasia, hematoma, or HSA [42]. Treatment is generally aimed at correcting the primary condition. Splenectomy is reserved for patients with serious splenic complications such as hemoabdomen [42]. Splenic infarction secondary to splenic torsion (with or without GDV) is discussed elsewhere.