Splenomegaly- Causes, Investigations and Treatment

Splenomegaly is an enlargement of the spleen due to any cause.

The spleen is an important organ located in the left upper quadrant of the abdomen, just below the diaphragm and next to the stomach.

It lies underneath the ninth, tenth, and eleventh ribs.

In a normal person, the spleen is not palpable. Not only this, the spleen has to be two and a half times its normal size to become palpable.

Therefore, a mildly enlarged spleen could be easily missed on routine clinical examination.

On exception is the ptosis of spleen or wandering spleen (caused by the loss or weakening of the ligaments that help to hold the spleen stationary), the spleen is palpable, though not enlarged.

Structure and Functions of Spleen

Spleen, in healthy adult humans, is about 7 cm (2.8 in) to 14 cm (5.5 in) in length. It usually weighs between 150 grams (5.3 oz) and 200 grams (7.1 oz). Normally, it is the size of an orange or a small fist.

An easy way to remember the anatomy of the spleen is the 1×3×5×7×9×11 rule.

The spleen is 1 by 3 by 5 inches (3 by 8 by 13 cm), weighs approximately 7 oz (200 g), and lies between the 9th and 11th ribs on the left-hand side.

The spleen contains two main regions of tissue called white pulp and red pulp.

• Red pulp: Contains venous sinuses (cavities filled with blood), and splenic cords (connective tissues containing red blood cells and white blood cells). It is responsible for filtering blood.
• White pulp: Mostly consists of immune cells (T cells and B cells) and is responsible for immune function.

Spleen performs various functions.

• It filters blood by removing old and damaged red blood cells. When blood flows into the spleen, red blood cells have to pass through narrow passages within the organ. Healthy blood cells can easily pass, however old or damaged red blood cells are broken down. The spleen also saves any useful components from the old blood cells such as iron, so as to reuse it in new red cell formation.
• It is a part of the lymphatic system and produces lymphocytes. Lymphocytes produce antibodies and help to prevent and fight infection.
• It acts as a reservoir for red blood cells and platelets, should the body need them.

Causes of Splenomegaly

Infective

Infections result in an increase in the defense activities of the spleen. There is an increased demand for clearing the antigens (of infectious organisms) from the blood leading to an increased number of reticuloendothelial cells. Infection also stimulates antibody production, causing lymphoid hyperplasia. These increased immune functions result in splenic hyperplasia and enlargement.

• Bacteria
  • Septicemia
  • Subacute bacterial endocarditis
  • Typhoid
  • Syphilis
• Viral
  • Infective hepatitis
  • infectious mononucleosis
• Protozoal
  • Malaria
  • kala-azar
  • Trypanosomiasis
• Fungal
  • Histoplasmosis

Congestive

In this, the spleen becomes engorged with blood because of impaired flow through the splenic vein, which empties into the portal vein.

• Congestive cardiac failure
• Constrictive pericarditis
• Budd Chiari syndrome
• Cirrhosis
• Schistosomiasis
• Sarcoidosis
• Congenital hepatic fibrosis
• Portal vein thrombosis

Blood Diseases

In hemolytic anemias, there is early and increased destruction of red blood cells. This increases the workload of spleen resulting in hyperfunctioning and splenomegaly.

Malignancies involving the bone marrow result in suppression of normal bone marrow activity causing decreased hematopoiesis. To compensate for this, compensatory extramedullary hematopoiesis (cell production outside the marrow) occurs within the spleen resulting in increased splenic activity causing splenomegaly.

Some malignancies also lead to infiltration of the spleen with tumor tissue. The tumor may arise from the cells present in the spleen or may metastasize to spleen from cancer originating elsewhere.  In either case, the end result is an enlarged spleen.

• Hemolytic anemia
  • Thalassemia
  • Spherocytic anemia
  • Sickle cell anemia
• Leukemias
• Lymphomas
• Myeloproliferative disorders
  • Myelofibrosis
  • Polycythemia rubra vera
  • Chronic myeloid leukemia

Infiltrative and Degenerative disorders

Accumulation of an abnormal substance within the spleen due to deficiency of certain enzymes or inability of the body to metabolize certain cellular constituents results in splenomegaly.

• Gaucher’s disease (accumulation of glucocerebroside)
• Niemann Picks disease ( accumulation of cholesterol and lipids)
• Amyloidosis ( accumulation of amyloid fibrils)

Neoplastic

• Hemangiomas
• Sarcomas
• Cysts
• Metastasis

Miscellaneous

• Connective tissue disorders
  • Systemic lupus erythematosus (SLE)
• Rupture of spleen and hematoma

Splenomegaly Associated with Other Conditions

Enlargement of spleen can be associated with many other conditions and presentations. for example, an enlarged liver could be associated with enlarged spleen.

Hepatosplenomegaly

Many conditions lead enlargement of liver as well as spleen. the causes are

• Infective: Malaria, kala-azar, infective hepatitis, Subacute bacterial endocarditis, infectious mononucleosis, disseminated tuberculosis
• Hematological conditions: Leukemias, lymphomas, chronic hemolytic anemias
• Congestive: Congestive cardiac failure, pericarditis, Budd-Chiari’s syndrome, portal hypertension
• Storage disorders: Glycogen storage disorders, amyloidosis
• Sarcoidosis

Splenomegaly with Jaundice

• Hemolytic anemia
• Cirrhosis of liver with portal hypertension

 Splenomegaly with Petechiae and Ecchymosis:

• Acute Leukemia, blast crisis in CML and CLL stage IV
• Subacute bacterial endocarditis
• SLE

Classification of Splenomegaly

Based on the extent of enlargement, splenomegaly can be divided into massive, moderate and mild.

Massive Splenomegaly

Spleen crosses umbilicus and midline (>8cm below the costal margin). Weight of the spleen is more than 1000 g.

Causes of massive splenomegaly include:

• Malaria, kala-azar
• Chronic myeloid leukemia
• Extrahepatic portal hypertension
• Myelofibrosis

Moderate Splenomegaly

Spleen extends between the costal margin and umbilicus (4-8 cm below the costal margin).

Causes of moderate splenomegaly include:

• All the above as in massive splenomegaly
• Hodgkin’s disease, leukemias, lymphomas, polycythemia rubra vera
• Hemolytic anemias
• Biliary cirrhosis
• Hemochromatosis
• Tumors and cysts
• Tuberculosis

Mild Splenomegaly

Spleen is just palpable (1-3cm below the costal margin).

Causes of mild splenomegaly include:

• All the above as in massive and moderate splenomegaly
• Acute infections: Typhoid, septicemia, Subacute bacterial endocarditis

What is Hypersplenism?

The term hypersplenism describes some of the sequelae that are often observed with splenomegaly.

Criteria for a diagnosis of hypersplenism include

• Anemia, leukopenia, thrombocytopenia, either singly or in combination.
• Normal or hypercellular bone marrow.
• Splenomegaly.
• Improvement in peripheral blood picture after splenectomy.

Symptoms of Splenomegaly

An enlarged spleen may cause:

• No symptoms in some cases
• Mild and vague abdominal discomfort. Pain or fullness in the left upper abdomen. The enlarged spleen can cause irritation of the diaphragm, resulting in pain radiating to the back and left shoulder blade.
• Hiccups can occur because of irritation of the diaphragm.
• Feeling of fullness even after eating a small amount and inability to eat large meals. This occurs because the enlarged spleen compresses the stomach.

Certain signs and symptoms can be caused due to the underlying diseases which result in an enlarged spleen. These include

• Fever (infection)
• Pallor, shortness of breath, bruising, and/or petechiae (blood diseases-hemolytic process)
• Weakness and weight loss (cancer)
• Nausea, vomiting, jaundice (liver disease)

Signs Suggestive of Enlarged Spleen

• Predominant left sided abdominal distension
• Splenic mass which moves downwards on inspiration
• A notch felt on the anterior border of the spleen

Diagnosis and Investigations of Splenomegaly

Physical Examination

By palpating or pressing the abdomen under the left ribcage, an enlarged spleen can be felt. Depending upon the size and extent of enlargement, various causes can be excluded or included. The doctor can also look for an enlarged liver by palpating on the right side of the abdomen or look for other signs of illnesses that cause splenomegaly.

Lab Investigations

Complete Blood Count

To evaluate the number of red cells, white cells, and platelets present in the circulation.

Liver Function Tests

To look for underlying liver disorders.

Hepatitis B and C testing

Lactate dehydrogenase (LDH)

Levels are increased in hemolytic anemias.

Erythrocyte sedimentation rate (ESR)

Increased ESR is seen in infections, acute leukemias, sarcoidosis, and other inflammatory disorders. Low ESR is seen in polycythemia vera, sickle cell disease, etc.

Peripheral Blood Film Examination

Peripheral blood film may show features of hemolysis including polychromasia, increased reticulocyte count, fragmented cells, etc. Presence of spherocytes, target cells or sickle cells may help to identify spherocytosis, thalassemia, sickle cell disease, and other hereditary hemolytic anemias. Features of myeloproliferative disorders or underlying bone marrow disorders may also be seen in peripheral smear examination.

Coagulation Profile

An abnormal coagulation profile with increased prothrombin time (PT), international normalized Ratio (INR) and partial thromboplastin time (PTT ) usually indicate an associated liver disorder. Cirrhosis and portal hypertension should be considered as the underlying cause.

Bone Marrow Aspiration and Biopsy

A needle is inserted into the pelvic bone and a sample of bone marrow is taken out. It helps to diagnose infiltrative disorders including cancers involving the bone marrow like leukemia or lymphoma.

Splenic Biopsy

This is not routinely done because of the risk of bleeding. If carried out, it may reveal any specific cause affecting the splenic tissue.

Ultrasound or Computerized tomography (CT) scan

It helps to determine the exact size and extent of the spleen.

Magnetic Resonance Imagining (MRI)

It helps to trace and visualize the blood flow through the spleen

Liver and Spleen Scan

A small amount of radioactive dye is injected into the arm.  The dye moves throughout the body and is collected in both of these organs. It helps to find the size and abnormalities present in these organs.

Treatment of Splenomegaly

Treatment of the Underlying Disorder

In many cases, splenomegaly is not a disease per se, but merely a manifestation of some other underlying disorder. Treating the underlying disease will cure the splenomegaly in such cases. This may involve treating any infection which is causing the spleen to enlarge.  Liver disorders and diseases of the blood need to be treated accordingly.

Watchful Waiting

If a person with enlarged spleen does not have any symptoms and no obvious cause can be found, the patient may be put on regular monitoring to look for the development of any specific signs and symptoms. High-impact sports activities like football, etc., should be avoided to prevent any injury to spleen.

Spleen Removal Surgery

If an enlarged spleen causes serious complications or the cause can’t be identified or treated, surgical removal of the spleen (splenectomy) should be carried out.

Patients with removed spleens can live an active life but are at an increased risk of acquiring infections; some of which may be life-threatening.

The following steps can reduce the risk of infection after splenectomy:

• The patients should be vaccinated both before and after the splenectomy. These include the pneumococcal, meningococcal and Haemophilus influenzae type b (Hib) vaccines, which protect against pneumonia, meningitis, and infections of the blood, bones, and joints. The pneumococcal vaccine needs to be administered every five years after surgery.
• Appropriate and timely antibiotics should be taken after the surgery and in the future whenever there is a possibility of an infection.
• The patient should avoid traveling to those parts of the world where certain infectious diseases are common.

Complications of Splenomegaly

Potential complications of an enlarged spleen are:

• An enlarged spleen traps a large number of blood cells within it. This can reduce the number of healthy white cells, red blood cells, and platelets present in the bloodstream. As a result, the patient may be prone to more frequent infections, anemia and increased bleeding.
• Ruptured spleen: An enlarged spleen is at risk of rupture as it grows beyond the protection of the rib cage. A minor injury may cause it to rupture and bleed into the abdominal cavity resulting in shock and even death.