Enlargement of spleen, ascites, jaundice, and the result of destruction of various blood cells by spleen – anemia, leukopenia, thrombocytopenia, gastrointestinal bleeding – may constitute the presenting symptoms.

The basic pathology is some kind of obstructive pathology in the portal, hepatic or splenic vein that causes obstruction of venous blood flow from the spleen towards the heart. The cause of such obstruction may be abnormalities present at birth (congenital) of certain veins, blood clots, or various underlying disorders causing inflammation and obstruction of veins (vascular obstruction) of the liver.

The standard system for classifying splenomegaly on radiography is:

- Normal (not splenomegaly): the largest dimension is less than 11 cm

- Moderate splenomegaly: the largest dimension is between 11–20 cm

- Severe splenomegaly: the largest dimension is greater than 20 cm

Also, a cutoff of a craniocaudal height of 13 cm is also used to define splenomegaly.

Splenomegaly refers strictly to spleen enlargement, and is distinct from hypersplenism, which connotes overactive function by a spleen of any size. Splenomegaly and hypersplenism should not be confused. Each may be found separately, or they may coexist. Clinically if a spleen is palpable, it means it is enlarged as it has to undergo at least twofold enlargement to become palpable. However, the tip of the spleen may be palpable in a newborn baby up to 3 months of age.

For children, the cutoffs for splenomegaly are given in this table, when measuring the greatest length of the spleen between its dome and its tip, in the coronal plane through its hilum while breathing quietly.

Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of "hypersplenism" which include; some reduction in the number of circulating blood cells affecting granulocytes, erythrocytes or platelets in any combination, a compensatory proliferative response in the bone marrow, and the potential for correction of these abnormalities by splenectomy. Splenomegaly is usually associated with increased workload (such as in hemolytic anemias), which suggests that it is a response to hyperfunction. It is therefore not surprising that splenomegaly is associated with any disease process that involves abnormal red blood cells being destroyed in the spleen. Other common causes include congestion due to portal hypertension and infiltration by leukemias and lymphomas. Thus, the finding of an enlarged spleen, along with caput medusa, is an important sign of portal hypertension.

Enlargement of the spleen is known as splenomegaly. It may be caused by sickle cell anemia, sarcoidosis, malaria, bacterial endocarditis, leukemia, pernicious anemia, Gaucher's disease, leishmaniasis, Hodgkin's disease, Banti's disease, hereditary spherocytosis, cysts, glandular fever (mononucleosis or 'Mono' caused by the Epstein-Barr Virus), and tumours. Primary tumors of the spleen include hemangiomas and hemangiosarcomas. Marked splenomegaly may result in the spleen occupying a large portion of the left side of the abdomen.

The spleen is the largest collection of lymphoid tissue in the body. It is normally palpable in preterm infants, in 30% of normal, full-term neonates, and in 5% to 10% of infants and toddlers. A spleen easily palpable below the costal margin in any child over the age of 3–4 years should be considered abnormal until proven otherwise.

Splenomegaly can result from antigenic stimulation (e.g., infection), obstruction of blood flow (e.g., portal vein obstruction), underlying functional abnormality (e.g., hemolytic anemia), or infiltration (e.g., leukemia or storage disease, such as Gaucher's disease). The most common cause of acute splenomegaly in children is viral infection, which is transient and usually moderate. Basic work-up for acute splenomegaly includes a complete blood count with differential, platelet count, and reticulocyte and atypical lymphocyte counts to exclude hemolytic anemia and leukemia. Assessment of IgM antibodies to viral capsid antigen (a rising titer) is indicated to confirm Epstein-Barr virus or cytomegalovirus. Other infections should be excluded if these tests are negative.

Splenic diseases include splenomegaly, where the spleen is enlarged for various reasons. On the other hand, a lack of normal spleen function is called asplenia.

Hepatosplenomegaly (commonly abbreviated HSM) is the simultaneous enlargement of both the liver (hepatomegaly) and the spleen (splenomegaly). Hepatosplenomegaly can occur as the result of acute viral hepatitis, infectious mononucleosis, and histoplasmosis or it can be the sign of a serious and life-threatening lysosomal storage disease. Systemic venous hypertension can also increase the risk for developing hepatosplenomegaly, which may be seen in those patients with right-sided heart failure.

An autosplenectomy (from" 'auto-' "self," '-splen-' "spleen," '-ectomy' "removal) is a negative outcome of disease and occurs when a disease damages the spleen to such an extent that it becomes shrunken and non-functional. The spleen is an important immunological organ that acts as a filter for red blood cells, triggers phagocytosis of invaders, and mounts an immunological response when necessary. Lack of a spleen, called asplenia, can occur by autosplenectomy or the surgical counterpart, splenectomy. Asplenia can increase susceptibility to infection. Autosplenectomy can occur in cases of sickle-cell disease where the misshapen cells block blood flow to the spleen, causing fibrosis and eventual atrophy of the organ. Autosplenectomy is a rare condition that is linked to certain diseases but is not a common occurrence.

The most frequent cause of autosplenectomy is sickle cell anemia which causes progressive splenic hypofunction over time. Increased deoxygenation causes sickling of red blood cells, which adhere to the spleen wall and splenic macrophages causing ischemia. This ischemia can result in splenic sequestration, where large amounts of blood pool in the spleen but do not flow within vasculature. This lack of blood flow can cause atrophy in the spleen and can lead to autosplenectomy.

Peliosis hepatis is an uncommon vascular condition characterised by multiple, randomly distributed, blood-filled cavities throughout the liver. The size of the cavities usually ranges between a few millimetres and 3 cm in diameter. In the past, it was a mere histological curiosity occasionally found at autopsies, but has been increasingly recognised with wide-ranging conditions from AIDS to the use of anabolic steroids. It also occasionally affects spleen, lymph nodes, lungs, kidneys, adrenal glands, bone marrow, and other parts of gastrointestinal tract.

Peliosis hepatis is often erroneously written "peliosis hepati"ti"s", despite its not being one of the hepatitides. The correct term arises from the Greek "pelios", i.e. discoloured by extravasated blood, livid, and the Latinized genitive case (hepatis) of the Greek "hepar", liver.

As the disease progresses, complications may develop. In some people, these may be the first signs of the disease.

- Bruising and bleeding resulting from decreased production of coagulation factors.

- Hepatic encephalopathy – the liver does not clear ammonia and related nitrogenous substances from the blood, which are carried to the brain, affecting cerebral functioning: neglect of personal appearance, unresponsiveness, forgetfulness, trouble concentrating, changes in sleep habits or psychosis may result. This can be seen on exam by asterixis, which is bilateral asynchronous flapping of outstretched, dorsiflexed hands seen in patients with hepatic encephalopathy.

- Sensitivity to medication caused by decreased metabolism of the active compounds.

- Acute kidney injury (particularly hepatorenal syndrome)

There are some changes seen in cirrhosis whose causes are not clearly known. They may also be a sign of other non-liver related causes.

- Nail changes.

- Muehrcke's lines – paired horizontal bands separated by normal color resulting from hypoalbuminemia (inadequate production of albumin). It is not specific for cirrhosis.

- Terry's nails (double nails) – proximal two-thirds of the nail plate appears white with distal one-third red, also due to hypoalbuminemia

- Clubbing – angle between the nail plate and proximal nail fold > 180 degrees. It is not specific for cirrhosis and can therefore can be due to a number of conditions

- Hypertrophic osteoarthropathy. Chronic proliferative periostitis of the long bones that can cause considerable pain. It is not specific for cirrhosis.

- Dupuytren's contracture. Thickening and shortening of palmar fascia (tissue on the palm of the hands) that leads to flexion deformities of the fingers. Caused by fibroblastic proliferation (increased growth) and disorderly collagen deposition. It is relatively common (33% of patients).

- Other. Weakness, fatigue, anorexia, weight loss.

A splenic injury, which includes a ruptured spleen, is any injury to the spleen. The rupture of a normal spleen can be caused by trauma, such as a traffic collision.

In minor injuries with little bleeding, there may be abdominal pain, tenderness in the epigastrium and pain in the left flank. Often there is a sharp pain in the left shoulder, known as Kehr's sign. In larger injuries with more extensive bleeding, signs of hypovolemic shock are most prominent. This might include a rapid pulse, low blood pressure, rapid breathing, paleness, and anxiety.

The symptoms of Felty's syndrome are similar to those of rheumatoid arthritis. Patients suffer from painful, stiff, and swollen joints, most commonly in the joints of the hands, feet, and arms. In some affected individuals, Felty's syndrome may develop during a period when the symptoms and physical findings associated with rheumatoid arthritis have subsided or are not present; in this case, Felty's syndrome may remain undiagnosed. In more rare instances, the development of Felty's syndrome may precede the development of the symptoms and physical findings associated with rheumatoid arthritis.

Felty's syndrome is also characterized by an abnormally enlarged spleen (splenomegaly) and abnormally low levels of certain white blood cells (neutropenia). As a result of neutropenia, affected individuals are increasingly susceptible to certain infections. Keratoconjunctivitis sicca may occur due to secondary Sjorgen's syndrome. Individuals with Felty's syndrome may also experience fever, weight loss, and/or fatigue. In some cases, affected individuals may have discoloration (abnormal brown pigmentation) of the skin, particularly of the leg, sores (ulcers) on the lower leg, and/or an abnormally large liver (hepatomegaly). In addition, affected individuals may have abnormally low levels of circulating red blood cells (anemia), a decrease in circulating blood platelets that assist in blood clotting functions (thrombocytopenia), abnormal liver function tests and/or inflammation of the blood vessels (vasculitis).

An accessory spleen ("supernumerary spleen", "splenule", or "splenunculus") is a small nodule of splenic tissue found apart from the main body of the spleen. Accessory spleens are found in approximately 10 percent of the population and are typically around 1 centimeter in diameter. They may resemble a lymph node or a small spleen. They form either by the result of developmental anomalies or trauma. They are medically significant in that they may result in interpretation errors in diagnostic imaging or continued symptoms after therapeutic splenectomy.

The primary symptom, hemorrhage, presents differently depending on the degree of injury, with the symptoms of major hemorrhage, shock, abdominal pain, and distention being clinically obvious. Minor hemorrhage often presents as upper left quadrant pain. Patients with unexplained left upper quadrant pain, particularly if there is evidence of hypovolemia or shock, are generally inquired regarding any recent trauma.

This condition affects less than 1% of patients with rheumatoid arthritis. The presence of three conditions: rheumatoid arthritis, an enlarged spleen (splenomegaly), and an abnormally low white blood cell count are indications that Felty's syndrome is possibly occurring. This condition as a whole is difficult to diagnose due to its complexity given a combination of disorders. It is commonly overlooked or misdiagnosed as other conditions (e.g., leukemia, systemic lupus erythrematosus) because of the rarity and lack of good understanding about it. An acronym can be used to make recognizing this disease somewhat easier:

S: Splenomegaly

A: Anemia

N: Neutropenia

T: Thrombocytopenia

A: Arthritis (rheumatoid)

The primary concern in any splenic trauma is internal hemorrhage, though the exact amount of hemorrhage may be small or large, depending on the nature and degree of injury. Small or minor injuries often heal spontaneously, especially in children. Larger injuries hemorrhage extensively, often causing hemorrhagic shock. A splenic hematoma sometimes ruptures, usually in the first few days, although rupture can occur from hours to even months after injury.

Hemolytic anemia or haemolytic anaemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular, but usually in the spleen). It has numerous possible consequences, ranging from relatively harmless to life-threatening. The general classification of hemolytic anemia is either inherited or acquired. Treatment depends on the cause and nature of the breakdown.

Symptoms of hemolytic anemia are similar to other forms of anemia (fatigue and shortness of breath), but in addition, the breakdown of red cells leads to jaundice and increases the risk of particular long-term complications, such as gallstones and pulmonary hypertension.

Accessory spleens may be formed during embryonic development when some of the cells from the developing spleen are deposited along the path from the midline, where the spleen forms, over to its final location on the left side of the abdomen by the 9th–11th ribs. The most common locations for accessory spleens are the hilum of the spleen and adjacent to the tail of the pancreas. They may be found anywhere along the splenic vessels, in the gastrosplenic ligament, the splenorenal ligament, the walls of the stomach or intestines, the pancreatic tail, the greater omentum, the mesentery or the gonads and their path of descent. The typical size is approximately 1 centimeter, but sizes ranging from a few millimeters up to 2–3 centimeters are not uncommon.

Splenogonadal fusion can result in one or more accessory spleens along a path from the abdomen into the pelvis or scrotum. The developing spleen forms near the urogenital ridge from which the gonads develop. The gonads may pick up some tissue from the spleen, and as they descend through the abdomen during development, they can produce either a continuous or a broken line of deposited splenic tissue.

Splenosis is a condition where foci of splenic tissue undergo autotransplantation, most often following physical trauma or splenectomy. Displaced tissue fragments can implant on well vascularized surfaces in the abdominal cavity, or, if the diaphragmatic barrier is broken, the thorax.

Symptoms include an enlargement in the size of the spleen, or a change from the spleen's original position to another location, usually in either other parts of the abdomen or into the pelvis. This ability to move to other locations is commonly attributed to the spleen's pedicle being abnormally long.

Physical factors may cause ischuria, constipation, as well as numerous spleen-related diseases such as hypersplenism, thrombocytopenia, and lymphoma. Blocking of the arteries and torsion in the spleen can also result in abdominal pain or swelling. However, lack of visible symptoms — except in incidents of abdominal pain — makes the disease difficult for doctors to diagnose, though medical imaging techniques such as medical ultrasonography, magnetic resonance imaging, or computed tomography can be used to confirm its occurrence.

Subphrenic abscess is a disease characterized by an accumulation of infected fluid between the diaphragm, liver, and spleen. This abscess develops after surgical operations like splenectomy.

Presents with cough, increased respiratory rate with shallow respiration, diminished or absent breath sounds, hiccups, dullness in percussion, tenderness over the 8th–11th ribs, fever, chills, anorexia and shoulder tip pain on the affected side. Lack of treatment or misdiagnosis could quickly lead to sepsis, septic shock, and death. It is also associated with peritonitis.

In general, signs of anemia (pallor, fatigue, shortness of breath, and potential for heart failure) are present. In small children, failure to thrive may occur in any form of anemia. Certain aspects of the medical history can suggest a cause for hemolysis, such as drugs, consumption of fava beans due to Favism, the presence of prosthetic heart valve, or other medical illness.

Chronic hemolysis leads to an increased excretion of bilirubin into the biliary tract, which in turn may lead to gallstones. The continuous release of free hemoglobin has been linked with the development of pulmonary hypertension (increased pressure over the pulmonary artery); this, in turn, leads to episodes of syncope (fainting), chest pain, and progressive breathlessness. Pulmonary hypertension eventually causes right ventricular heart failure, the symptoms of which are peripheral edema (fluid accumulation in the skin of the legs) and ascites (fluid accumulation in the abdominal cavity).

Wandering spleen is most commonly diagnosed in young children as well as women between the ages of 20 and 40. Even so, the disease is very rare and fewer than 500 occurrences of the disease have been reported as of 2005, of which around 148 (including both children and adult cases) were documented to have been from between 1960 and 1992. Less than 0.5% of all splenectomies, surgical removal of the spleen, are performed due to having this disorder.

Characteristics of the disorder include the loss, weakening, or malformation of the ligaments that help to keep the spleen located in the upper left part of the abdomen. Though not a genetic disease, wandering spleen is often found at birth. It can occur in adults as the result of injuries and other similar conditions that cause the ligaments to weaken, such as connective tissue disease or pregnancy. Wandering spleen (splenoptosis) predisposes the spleen to complications such as torsion, splenic infarction, pancreatic necrosis and rarely pseudocyst formation.

In 1992, the youngest case of the literature of torsion of wandering spleen at two days of birth was reported in Lebanon, by Dr Edouard Sayad.