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The Indications for Medical and Surgical Management of Splenic Disease.

The spleen is a relatively large organ with wide-ranging and various functions.  In general, the spleen is tongue shaped, has a mottled reddish brown color and occupies the left cranial quadrant of the abdomen.  While the spleen is not essential for life, its contributions to maintaining bodily homeostasis are beginning to be better understood as research has begun to shed more light upon the pathophysiology of other disease processes which may affect splenic function.  The four basic tenets of splenic function include erythrocyte conditioning and maintenance, erythrocyte and platelet storage, extramedullary hematopoiesis, and plasma filtration for the presence of antigens.  Thus, removing the spleen should not be considered as a procedure without consequence. 

As an organ of erythrocyte maintenance, the spleen processes the final stages of erythrocyte maturation, detects and removes abnormal intracellular particulate matter during the process of pitting, and helps cull aged erythrocytes out of circulation.  Newly developed immature erythrocytes spend several days in the spleen where remaining intracellular material is removed, the cell membrane is reshaped into the typical disc, and the cell is reduced in size before joining the circulating blood pool.  During the process of pitting the macrophages detect and remove abnormal intracellular materials.  The pitted materials removed include but are not limited to intracellular parasites, remnants of nuclear material (Howell-Jolly bodies), denatured hemoglobin (Heintz bodies), and other types of intracellular debris.  The relatively large population of erythrocytes and leukocytes circulating within the spleen creates an anaerobic environment; this relatively anaerobic environment results in the cell membrane of damaged, abnormal and older erythrocytes to become less pliable.  These cells become too stiff and are therefore unable to undergo the deformation required to pass into the splenic sinuses.  Macrophages then cull these cells out of circulation to recycle the iron back to the bone marrow. 

While the reservoir capacity of the spleen for erythrocytes may vary from one species to the next, the canine and feline spleen have a large storage capacity estimated to fall between 10 to 20% of the circulating red blood cell mass.  In addition, the spleen can store up to 30% of the entire platelet mass.  Within the spleen there are three pools in which the red blood cells circulate.  The majority (~90%) of the circulating blood enters the rapid pool and traverses through the organ in about 30 seconds.  Approximately 9% of the red blood cells enters the intermediate pool and circulates through within eight minutes.  The remaining 1% traverses through the slow pool, which can take nearly an hour to complete its circulation through the spleen.  Under conditions of stress, hypoxemia, heavy exercise and excessive blood loss, up to 98% of the blood volume is shifted to the rapid pool through splenic contraction to significantly increase the blood volume.

During fetal development, the spleen functions as an organ of hematopoiesis.  Normally, these hematopoietic abilities cease at birth as the bone marrow assumes this role.  A limited capacity for hematopoiesis, however, is preserved in the adult animal.  While splenic extramedullary hematopoiesis is uncommon in the cat, in dogs splenic hematopoiesis can occur with any one of a number of disease processes in which the numbers of erythrocytes become compromised.  These processes include infiltrative myeloproliferative diseases, immune-mediated hemolysis, chronic inflammatory conditions, infectious diseases and malignant disease processes. 

As an organ of filtration the spleen is the single largest reticuloendothelial system in the body.  It plays a major role in filtering and clearing blood borne microorganisms as well as initiating an immunologic response to offensive circulating antigens.  In addition to phagocytosis and IgM production, other mediators of immunity are synthesized which enhance both neutrophilic phagocytosis and the activation of the complement pathway. While both the liver and spleen filter microorganisms, the splenic filtration is more effective in removing poorly opsonized bacteria. 

The processes that lead to splenic enlargement (splenomegaly) are varied. Splenic enlargement may be diffuse and generalized encompassing the whole spleen, or localized involving only portions of the spleen at one time.  It should be mentioned, however, that the mere presence of splenomegaly does not necessarily result from disease processes which require medical intervention.  Several different mechanisms which affect the splenic parenchyma may result in generalized splenomegaly.  These mechanisms include inflammation, cellular hyperplasia, congestive enlargement, or cellular infiltration.  The process which leads to inflammatory splenomegaly depends on the type of cells predominantly found in the enlarged spleen. Infectious splenitis is commonly associated with neutrophilia secondary to bacterial infections from various sources including but not limited to penetrating abdominal wounds, migrating foreign bodies, and by hematogenous means.  Protozoal, viral, and mycotic infectious organisms can also lead to infiltrations with various other inflammatory cells. As part of the reticuloendothelial system, the spleen may become hypertrophic and/or hyperplastic in response to blood-borne antigens, or through the destruction of erythrocytes.  This is the result of an increase in the lymphoreticular populations.  Common subacute and chronic disease processes which lead to hyperplastic splenomegaly include immune-mediated hemolytic anemia, immune-medicated thrombocytopenia, drug induced hemolytic anemia and hemobartonellosis.

Generalized splenomegaly can also be caused by various vascular changes which occur through both normal and abnormal physiological conditions.  Vascular distention secondary to smooth muscle cell relaxation in the splenic capsule is associated with certain sedatives and can lead to pooling of as much as 30% of the circulating blood volume. Congestion of the spleen is a common consequence of vascular outflow obstruction as seen in cases of torsion of the splenic vascular pedicle and in splenic and portal vein thrombosis.  Regardless, any pathologic process which lead to portal vein/caudal vena cava hypertension and any lesion which restricts venous blood flow away from the spleen will lead to generalized splenomegaly. 

Infiltration of the spleen by nonsplenic cells may also lead to generalized splenomegaly.  Extramedullary hematopoesis in the spleen commonly occurs when a pathologic process undermines the ability of the bone marrow to function normally or through any other various stimuli which requires the body to increase the red blood cell population.  Neoplastic cells of various lineages may infiltrate the spleen as either a primary tumor or as a metastatic disease.  Common neoplastic processes which typically produce generalized splenomegaly include myeloproliferative disease, lymphosarcoma, and mastocytosis.  In the cat, mastocytoma and lymphosarcoma are the most commonly observed neoplastic processes of the spleen. 

In contrast to generalized splenomegaly, localized splenic enlargement is a much more common occurrence in dogs than in cats.  In dogs, 51% of localized lesions are classified as non-neoplastic, whereas 48% are neoplastic.  While non-neoplastic masses are slightly more common than neoplastic masses, they are indistinguishable at the time of surgery.  As observed with any other neoplastic process, splenic neoplastic masses can be either benign or malignant and primary or metastatic.  The most commonly seen non-neoplastic splenic masses are hematomas and nodular hyperplasia.  Other causes of non-neoplastic causes of a splenic mass include abscesses, cysts and infarctions, but these lesions are very uncommon. 

Although splenic hematoma and nodular hyperplasia are categorized as separate entities, recent histopathologic evaluation of the two masses suggests that they are linked and represent a continuum.  A high percentage of non-neoplastic lesions contain elements compatible with both diagnoses.  Hyperplastic nodules in the spleen are composed of various cellular components including lymphoid, hematopoietic, and plasmacytic cell populations, whereas the splenic hematoma consists of hemorrhage, organizing fibrin, and degenerative erythrocytes.  The failure of marginal zone circulation secondary to nodular hyperplasia results in an accumulation of blood within the hyperplastic nodule, and may eventually lead to hematoma formation. 

The most commonly observed neoplastic lesion in the dog is hemangiosarcoma.  This malignant disease process carries a poor long term prognosis. Metastasis at the time of surgery is present in as many as 65% of the dogs.  Many other histologic types of cancer constitute the remaining canine splenic neoplasms, including leiomyosarcoma, undifferentiated sarcomas, fibrosarcoma, osteosarcoma, liposarcoma, myxosarcoma, chondrosarcoma, rhabdomyosarcoma, and malignant fibrous histiocytoma.  Cats develop different types of splenic tumors; lymphosarcoma, mast cell tumor, and myeloproliferative diseases accounted for 30% of neoplastic diagnoses, whereas hemangiosarcoma accounted for only 3%. 

The diagnostic evaluation of animals with suspected splenic disease begins with routine abdominal radiography.  The spleen is normally well visualized on plain abdominal radiographs, but there is a wide variation in its appearance.  On the ventrodorsal view the spleen is normally a triangular structure on the left side of the abdomen between the gastric fundus and the left kidney.  The size and location of the spleen are more variable on the lateral view; however, in general it has a triangular, oval, or rounded appearance and is caudal to the liver.  Radiographic splenomegaly can be secondary to generalized splenic enlargement or to a localized mass.  Splenic masses are the primary differential diagnosis for mid-abdominal masses in dogs and cats, however, other considerations are masses associated with the liver, intestinal tract, mesentery, adrenal glands, mesenteric lymph nodes, kidneys, or reproductive structures.  Ultrasonography constitutes the noninvasive procedure of choice to evaluate splenomegaly and to characterize the lesion and potential causes of splenic enlargement.  Abdominal ultrasonography can reveal diffuse splenomegaly, localized splenic masses, splenic congestion, and evaluate the abdomen for metastatic disease.  Color-flow Doppler ultrasound can detect vascular compromise with torsion of the splenic pedicle or portal vein congestion, as well as congestion secondary to cardiac or liver disease. Percutaneous sampling of the spleen is possible by fine needle aspiration with a low risk of significant complications.  Abdominal ultrasound can be used to guide the aspiration if the localized splenomegaly is not easily palpated.  Cytologic evaluation can be used to determine the need for surgery, further diagnostics, or therapy.  Although the ultrasound represents a major advance in evaluation of the spleen, it is not infallible. In some situations, the extent of the lesion or adhesions between the diseased spleen and adjacent organs can limit the diagnostic accuracy of ultrasonagraphy.  Both computed tomography and magnetic resonance imaging are useful for the evaluation of splenomegaly and concurrent underlying disease processes. Neither modality is commonly used in the diagnosis of splenic disorders because of the time and financial commitments involved in utilizing either one. 

The majority of the clinical signs of dogs and cats associated with disorders of the spleen are related to the underlying disease process.  These clinical signs may be vague and nonspecific and include anorexia, weight loss, abdominal discomfort and/or distention, vomiting, weakness/collapse and polyuria/polydipsia (PU/PD).  PU/PD is relatively common in dogs with marked splenomegaly, particularly in those with splenic torsions.  The mechanisms of PU/PD are not well understood, however, clinical signs usually resolve after splenectomy.

The most common splenic conditions which require surgical intervention include splenic laceration/trauma, torsion and the removal of splenic masses.  Splenic torsions occur most commonly in large/giant breed dogs with a deep chested confirmation.  The spleen rotates around its vascular pedicle and results in venous obstruction and eventually splenomegaly.  It is a condition commonly associated with gastric dilation-volvulus syndrome; however, it can occur as an isolated condition as well.  Splenic torsion can present either as an acute or a chronic condition.  Dogs experiencing the acute condition can exhibit significant abdominal pain and discomfort, excessive salivation and signs of cardiovascular failure which can lead to shock and collapse within several hours.  Patients experiencing the more chronic condition may present with non-specific signs of vomiting, anorexia, intermittent abdominal pain, abdominal distension, weight loss, and polyuria and polydipsia.  In general, laboratory findings usually do not contribute tremendously to the diagnosis. Packed cell volume may be in the low to normal range and concurrent thrombocytopenia may be present.  In addition, leukocytosis with neutrophilia may be present.  Anemia may be secondary to red blood cell destruction or splenic sequestration, whereas thrombocytopenia may be secondary to platelet sequestration or associated with the development of disseminated intravascular coagulopathy.  Hemoglobinuria is a common finding and pale mucous membranes are observed with both acute and chronic splenic torsions.  Regardless of the duration of the splenic torsion, surgical removal of the spleen is indicated. 

Substantial splenic trauma must be considered as a differential diagnosis for animals with hemoabdomen and a history of either blunt or penetrating abdominal injuries. While blunt abdominal trauma is thought to be the most common cause of splenic trauma, lacerations of the spleen can occur but with less frequency relative to blunt force. Whereas hemorrhage secondary to lacerations and blunt parenchymal lesions is not a major cause of morbidity in dogs and cats, trauma or lacerations involving the major splenic arteries and veins can be fatal, especially in the absence of medical support and surgical intervention.  The true impact of splenic hemorrhage secondary to laceration or blunt trauma remains to be seen and is underappreciated because a large portion of dogs and cats receiving fatal abdominal trauma may not present to a veterinary facility in a timely manner.  The presenting signs and laboratory and radiographic findings depend on the rate and amount of blood loss before presentation as well as the presence of concomitant injuries.  Supportive medical treatment including intravenous fluid administration, abdominal compression bandaging, and serial monitoring of the animal’s packed cell volume and circulatory status is the first line of stabilization.  Failing parameters are further treated by transfusion of appropriate blood products, and surgical intervention is considered when appropriate medical therapy fails to sustain stability of the patient.

The approach to treating splenic masses is based on clinical signs, the patient’s immediate medical condition, and the presence or absence of definable metastatic lesions on either thoracic and abdominal radiography and/or ultrasonagraphy. Echocardiography (ultrasound of the heart) is often recommended as up to 15% of dogs with malignant hemangiosarcoma may have tumor spread to the right atrium on initial presentation.  An ECG to look for arrhythmias may also be required especially after surgery.  Up to 24% of dogs with splenic hemangiosarcoma have arrhythmias and these may not be noted until after surgery.  While this may require treatment, most resolve within 24-48 hours. As mentioned previously, a dog with a splenic mass may display a variety of clinical symptoms which depends upon the underlying nature of the mass. Most dogs present initially with acute signs associated with tumor rupture and bleeding into the abdominal cavity.  If the mass is neoplastic, the patient can exhibit more systemic signs because of cachexic changes which can accompany malignancy. Regardless, if the mass is actively bleeding, the patient is considered an immediate surgical candidate as splenic removal is the only way to prevent continued intra-abdominal hemorrhage. Common clinical signs observed include decreased appetite or anorexia, weight loss, vomiting, abdominal distention with or without a fluid wave, abdominal discomfort, cardiac arrhythmias, pale mucous membranes, lethargy, and a palpable mass in 30-62 % of dogs. Whereas some factors, such as anorexia and hemoperitoneum are significantly more common in dogs with hemangiosarcoma, one third of all dogs with hemoabdomen have a benign hematoma; therefore, the presence of internal abdominal bleeding is not necessarily diagnostic of malignant cancer. Complete splenectomy is currently recommended for splenic masses.  A careful and complete abdominal exploratory is indicated to identify any possible metastatic lesions.  Metastasis of splenic tumors to the liver is common, and suspicious liver lesions should be sampled, and if possible, removed.  However, benign liver lesions such as extramedullary hematopoiesis and nodular hyperplasia are also common in dogs with splenic tumors and the surgeon must avoid the temptation to prematurely label a hepatic lesion as metastatic and therefore indicative of a malignant process. Basing immediate therapeutic actions on the presence of gross hepatic lesions can therefore result in an inappropriate diagnosis and prematurely lead to dogs being humanely euthanized when in fact they may have an excellent prognosis. Because more than 50% of splenic masses are benign, complete histopathologic evaluation and confirmation of a malignant process should precede a recommendation for euthanasia.  As the abdominal cavity is the main site of tumor recurrence, most dogs with malignant splenic cancer will die or be euthanized due to complications associated with progressive tumor growth within the abdominal cavity. Current standard treatment for dogs with hemangiosarcoma is surgery and systemic (intravenous) doxorubicin-based chemotherapy. Despite the most effective available treatments for this disease, most dogs will succumb to their tumor, and the average survival is approximately 6 months to one year. Other potential sites of metastasis can include the mesenteric, gastric, sternal and tracheobronchial lymph nodes as well as the prostate, diaphragm, lung, kidney, bladder, bone marrow, and intestines. 

In summary, while many general practitioners will visualize a mass effect involving the spleen and inform the client that their pet has a malignancy requiring euthanasia because of a poor prognosis, the truth is that this statement is accurate in only approximately 50% of the cases. As with any other organ the spleen is susceptible to the development of both benign and malignant disease processes. For this reason, many pets are inappropriately euthanized when in fact they may have a good to excellent prognosis with surgical removal of the affected spleen. As mentioned previously, regardless of histological origin both benign and malignant tumors can rupture without warning, and consequently lead to profuse blood loss, hypovolemia and eventual death. From a client’s perspective, one should understand that while the spleen functions to help maintain homeostasis of various bodily systems it is not necessary for survival. Depending on the stage of the pathologic state present, the splenic problem may or may not be life threatening without urgent care.  Appropriately staged diagnostic, medical and surgical intervention with or without adjunctive follow-up therapy may allow many pets the opportunity to achieve additional quality longevity free from pain or discomfort or to be completely cured.
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Intraoperative view of ruptured spleen

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