Mario Brown Arnold

It is accepted that the spleen, in addition to being the seat of numerous diseases, also fulfills a wide range of functions.

Anatomy and physiology

The spleen is a solid organ of 7.5 cm wide x 12 cm long, with an average weight of 150-180 g. It is located in the abdomen, in the left subphrenic cell, and located in such a way that it is difficult to palpate it under normal semiological conditions. That is why any frank palpation of the spleen suggests an increase in size with a probable pathology. This organ is only evident when its volume increases around 40% above normal size.

From the histological point of view it consists of a capsule, a diffuse conjunctiva, and a framework of trabeculae that enter the organ's hilum. The interior is made up of lymphoid follicles that are lymphoblasts in its center and lymphocytes on the periphery, forming the white pulp in opposition to the rest, which due to its viscous red color is called red pulp. The latter integrates most of the splenic parenchyma and is made up of the Billroth cords and the venous sinuses that limit them. The mononuclear cells in Billroth's cords are called splenocytes and are histiocytic reticular cells. Arterial circulation is given by the splenic artery, which branches to feed the venous sinuses and Billroth's cords  then draining into the splenic vein and flowing into the portal circulation.

It is a lymphoid organ that participates in the formation of antibodies. This function seems to be more important in children than in adults, since splenectomy increases the incidence of bacterial infections in the former. The destruction of aged red blood cells takes place in the spleen and is called hemocatheresis.

A third of the circulating platelets, the youngest, are retained in the splenic circulation; This will only have repercussions in cases of splenomegaly, clinically manifesting as thrombocytopenia because the greater the splenic size, the greater the volume of trapped platelets.

During embryonic life, the spleen has a hematopoietic function, which only "potentially" persists in adulthood and may become apparent in functional disturbances of the bone marrow. In these circumstances, the spleen can resume its blood cell-forming function in an intense supplement called extramedullary hematopoiesis.

Pathophysiology

Spleen conditions are evidenced by an increase in size called splenomegaly.

Any cause that causes congestion of the splenic circulation and any stimulus that produces proliferation, replacement or infiltration of the lymphoreticular elements of the white pulp and of the Billroth cords will be the cause of splenomegaly. Splenomegaly can be originated byseveral mechanisms:

1. Congestive splenomegaly. They are observed whenever there is an increase in pressure in the portal circulation, as in Banti syndrome (congestive heart failure, liver cirrhosis, portal or splenic thrombosis, etc.).
2. Parenchymal splenomegaly. They result from the proliferation of normal, neoplastic, or hemopoietic cellular elements. The proliferation of normal cellular elements is seen in inflammatory processes: acute infections (typhoid fever, sepsis, bacterial endocarditis, mononucleosis), chronic infections (tuberculosis, syphilis, brucellosis, histoplasmosis, malaria, Chagas) and other non-infectious diseases such as collagen diseases (lupus erythematosus, rheumatoid arthritis, sarcoidosis), hemolytic anemias and in thrombocytopenic and idiopathic purples. Neoplasms produce proliferation and infiltration of atypical cellular elements; the most frequent are lymphomas and leukemias.
3. Infiltrative splenomegalies. They are caused by excessive storage of normal and abnormal metabolic products: Gaucher disease, Niemann-Pick disease, hemosiderosis and amyloidosis.

Interrogation

Splenomegalies of possible congestive cause should guide the hierarchy of all portal hypertension etiologies. It will then be necessary to search for a history of chronic alcohol intake, hepatotoxic drugs, viral liver infections (hepatitis), symptoms of congestive heart failure (dyspnea, generalized edema).

More numerous are the diseases capable of producing parenchymal splenomegaly, either due to the proliferation of its normal cellular elements, or to the replacement of these by neoplastic cells or hemoproliferative cells.

The proliferation of normal cellular elements is generally due to inflammatory processes, whether infectious or not, such as collagenopathies. The search for infections should be directed first to determine if they are acute or chronic. In the first case, a history of ingesting non-potable water, and the presence of gastrointestinal, cardiac, and neurological symptoms, will be important data for thinking about typhoid fever. An evolution with prolonged fever or the knowledge of having carried out invasive angiological studies because of valve disease, drug addiction, valve replacement surgery, suggest a bacterial endocarditis. A feverish condition with generalized cramping, impairment of general condition, and a close history of gynecological or abdominal surgery may suggest anaerobic or gram negative sepsis.

If chronic infections are suspected, contact with tuberculosis patients should be ranked (notion of focus), and in these circumstances promiscuity and low socioeconomic status are predisposing factors. Multiple and heterogeneous sexual contacts are important factors in syphilis, while rural and refrigerator jobs are common antecedents in brucellosis patients. The house and the geographical area where it is inhabited are important antecedents for Chagas disease and malaria.

Evidence of fever with multiple affected organs: arthritis, polyserositis, skin lesions, cough, Raynaud's syndrome, suggests a disease of collagen (systemic lupus erythematosus, rheumatoid arthritis). Anemia and jaundice with splenomegaly are characteristic of hemolysis. The presence of polyadenopathies with hypertemia, weight loss, itching without skin lesions, night sweats, anemia and hemorrhagic diathesis is typical of lymphomas and leukemias.

Benign splenic cysts and tumors are not accompanied by systemic manifestations, since if they present symptoms they will be a consequence of local growth (true or false cysts, hemangiomas). Metastases from malignant tumors of the spleen are  rare, most often from adjacent organs such as the stomach.

Splenomegaly accompanied by anemia or bleeding manifestations is observed in those cases in which the splenic parenchyma is replaced by hemopoietic cells, as in myeloproliferative syndromes (myelofibrosis, polycythemia vera, chronic myeloid leukemia).

An unexplained or concomitant enlargement of the spleen with bone pain, mainly in the long bones and with difficulty in walking, should lead to the suspicion of Gaucher disease, a metabolic disorder characterized by deposits and infiltration of glucocerebrides in the spleen and characteristic bone lesions. Young children with hepatosplenomegaly and a history of repeated episodes of bronchopulmonary infection may be carriers of Niemann-Pick disease. This, like Gaucher disease, is a disorder of the metabolism of glucocerebrósis. The spleen can be enlarged by infiltration in other systemic diseases such as amyloidosis, histiocytosis, and hemosiderosis.

Splenomegaly as the only finding

1. Chronic infection
   • Chagas disease
   • Malaria
2. Neoplasms
   • Lymphomas
   • Chronic myeloid leukemia
   • Metastatic carcinomas (rarely)
3. Benign tumors
   • Cysts
   • Vascular tumors (hemangiomas)
4. Metabolic
   • Gaucher disease
   • Niemann-Pick disease
   • Amyloidosis
   • Hemosiderosis

Splenomegaly associated with different clinical syndromes

1. Fever
   • Infection:
     • Bacterial: bacterial endocarditis, tuberculosis, syphilis, brucellosis, salmonellosis, sepsis
     • Virotic: infectious mononucleosis, hepatitis, rubella.VIH infection.
     • Parasitic: malaria, Chagas disease, toxoplasmosis
     • Fungal:: candidiasis, etc.
   • Collagenopathies:
     • Systemic lupus erythematosus
     • Rheumatoid arthritis and its variants
   • Neoplasms.
     • Hodgkin and non-Hodgkin lymphoma
     • Acute and chronic leukemias.
2. Adenopatías
   • Malignant blood diseases: acute lymphoblastic leukemia, chronic myeloid leukemia, chronic lymphoid leukemia, lymphomas
   • Acute viruses: infectious mononucleosis, rubella.VIH is mainly sub acute to chronic.
   • Parasitosis: toxoplasmosis
   • Ingestion of drugs: diphenylhydantoin
   • Granulomatous diseases: sarcoidosis
3. Anemia
   • Malignant blood diseases: lymphomas, chronic myeloid leukemia, acute lymphoid leukemia
   • Myelodysplastic syndromes: polycythemia
   • Hemolytic anemias (thalassemia)
   • Chronic infection
   • Bacterial endocarditis
   • Collagenopathies (systemic lupus erythematosus)
   • Idiopathic thrombocytopenic purpura
4. Hepatomegalia
   • Chronic liver disease: cirrhosis, Budd-Chiari syndrome, chronic active hepatitis
   • Infections: sepsis from any cause
   • Malignant blood diseases: lymphomas, chronic myeloid leukemia
   • Metabolic diseases: hemochromatosis, Gaucher, etc.
5. Jaundice
   • Chronic liver disease
   • Hemolytic anemia
6. Edema
   • Ascites-edematous syndrome (liver cirrhosis)
   • Budd-Chiari syndrome
   • Congestive heart failure

Study methodology

In all patients it is necessary to carry out a series of so-called routine studies.

The clinical doctor has three instruments to guide the diagnosis of a disease: the laboratory, imaging methods and histopathology. With them a pathway  must be followed that generally culminates in the biopsy study.

Data to be obtained initially in all patients with splenomegaly

• CBC
• Erythrosedimentation
• Glucemia
• Uremia
• Uricemia
• Cholesterolemia
• Proteinogram electrophoretically
• transaminases (glutamic oxaloacetic and glutamic pyruvic)
• Alkaline Phosphatase
• Bilirubinemia
• Prothrombin
• Urine full
• chest X-ray (front and profile)

Infections. The bacteriology laboratory, through the multiple cultures that can be performed, is the key in most cases. In certain infections whose etiologic agent is difficult to isolate due to various causes, the search for circulating antibodies and specific serological tests may give clues about the disease-producing agent (Chagas disease, hepatitis A and B,and also VIH). Imaging methods do not establish a cause or etiological diagnosis; they only provide information such as size, density, location, involved organs (chest radiograph in tuberculosis, echocardiography in bacterial endocarditis, computed axial tomography in liver abscesses, etc.).

Histopathology is not an essential element in these cases, and its use is limited in practice to the diagnosis of certain infections by opportunistic microorganisms or in cases of infections resistant to antibiotic treatment in which the producing agent is unknown. Other times a surgical biopsy will unexpectedly show a chronic tuberculous or fungal infection that had not been suspected.

Collagenopathies. Antinuclear antibodies (antinucleus factor, anti DNA, LE cells) and rheumatoid factor are important in systemic lupus erythematosus and rheumatoid arthritis. The decrease in complement (total and fractions) is observed in patients with systemic lupus erythematosus and active nephritis.

Among the diagnostic imaging methods, bone radiography, which shows typical injuries to the extremities and large joints in patients with rheumatoid arthritis, is useful.

The biopsy study will confirm, in systemic lupus erythematosus, the presence of vasculitis in the skin and muscle and the characteristic glomerular lesions at the kidney level. In the case of joint conditions, the biopsy will clarify the etiology if it demonstrates the classic inflammatory phenomenon called "pannus", typical of rheumatoid arthritis.

Neoplasms. Imaging methods are useful because they detect lesions that take up space, and allow us to know their existence, limits and size, along with other probable locations that are asymptomatic. The scintigraphy is suitable for studying neoplastic lesions of the skeleton. Computed axial tomography is useful to detect intracranial lesions, in the mediastinum and the abdominal cavity. images of the entire body between. Abdominal ultrasound performs similar functions as computed axial tomography, with lower image resolution but at a considerably lower cost. Conventional radiology provides reasonable resolving power to the lung fields and is useful in the study of abdominal lymph nodes using lymphography but thie method has been completely replaced by CT Scan and PET-CT.

Tissue biopsy is the only way to confirm the presence of a neoplasm, since no other study can replace it in the diagnosis of these diseases.

Blood diseases. The role of the laboratory is fundamental since the diagnosis of many hematological diseases, mainly anemias, depends on a morphological study given by direct examination under a microscope. Other tests such as measurement of serum iron, hemoglobin electrophoresis, determination of hemosiderin in urine and serum haptoglobins, and deficiencies of vitamins B12 and folic acid serve to diagnose iron deficiency, thalassemia, hemolytic anemia and anemia. megaloblastic. Bone marrow biopsy is important since most of the alterations capable of producing abnormalities in some of the blood series originate from or affect it.

Obtaining bone marrow material is extremely necessary to proceed with the study of immunohistochemistry and cytogenetics, absolutely necessary for the differential diagnosis of acute leukemias and to confirm typical cytogenetic alterations (Philadelphian chromosome) in chronic leukemias.

Metabolic diseases. The diagnosis is reached by biopsy. Care should be taken to order a Congo red stain if you want to investigate amyloidosis.

Diseases that cause splenic congestion. Laboratory tests that are of some use are liver function studies, and antigens and antibodies to hepatitis A and B viruses, all aimed at detecting chronic liver disease or hepatitis of viral origin.

Conventional radiology (gastroduodenal series) can show esophageal varices as a manifestation of portocava hypertension. Splenoportography measures capillary pressure in the portal circuit. Ultrasonography, hepatosplenic scintigraphy and axial computed tomography of the abdomen may show liver retraction with areas of different parenchymal density in the case of cirrhosis and splenomegaly.

Computed axial tomography in its multislice mode shows, in 3D reconstruction, the arterial and venous blood vessels with great definition, being useful for defining vascular causes of splenomegaly (thrombosis, embolisms).,making it one of the most useful studies today

Positron emission tomography with image fusion using glucose fluoride makes it possible to use images of uptake of said tracer (only taken up by pathological tissues, neoplasms, inflammation from other causes) and merge them with images obtained by tomography. Approved for diagnosing the spread of Hodgkin's disease and other lymphomas, this method is also very useful in evaluating response to treatment.

In the context of splenomegaly without apparent cause, the appearance of hypermetabolic areas in the spleen are suggestive of neoplastic pathology, possibly lymphoma.

Splenomegaly can be seen as part of a picture of congestive heart failure, but in those cases the diagnosis is eminently clinical.

Drug ingestion: The history of ingestion of certain drugs such as diphenylhydantoin capable of producing changes in the hematopoietic sector should be ranked.

Studies to be requested according to the guidance provided by the clinical examination and initial determinations.

• Infections
  • Cultures: blood, urine, faeces, jaws.. Parasitological examination of fecal matters.
  • Serology: for fungi, viruses, bacteria and parasites. Circulating antibodies.
  • Biopsy: for culture and specific stains.
  • Imaging methods: they allow to locate lesions and help to plan the therapy.
  • Laboratory: antinucleus factor (FAN), anti-DNA, LE cells, complement (C3-C4), latex test, serum and urinary immunoelectrophoresis.
• Collagenopathies
  • Biopsy: detection of typical skin, vessel, kidney, and synovial lesions.
  • Imaging methods: they are of little use.
  • Laboratory: Peripheral blood examination by a hematologist. Proteinogram by electrophoresis (serum and urinary). Immunological evaluation by skin tests: PPD, candidin, dinitrochlorobenzene.
• Neoplasms
  • Biopsy: anatomopathological study, Cytogenetic studies in cultures. Monoclonal antibodies. Immunohistochemical techniques.
  • Imaging methods: they are complementary to each other. They assess the location and extent of the disease.
• Blood diseases
  • Laboratory: blood count by a hematologist. Studies on iron metabolism. Guaiac test. Hemosiderin in urine. Hemoglobin electrophoresis. Folic acid and vitamin B12.
  • Biopsy: to confirm a diagnosis (bone marrow).
  • Imaging methods: radiosotopic study of erythrocyte and platelet half-life.
• Metabolic diseases
  • Biopsy: bone and liver for Gaucher and Niemann-Pick. Mucosa for hemochromatosis and Congo red staining for amyloidosis.
  • Imaging methods: bone radiographs. Ultrasonography. Scintigrams. Computed axial tomography.
  • Laboratory: liver function tests. Virological studies for hepatitis.
• Congestive
  • Biopsy: liver (rule out liver disease).
  • Diagnostic imaging methods: esophagogastroduodenal serial radiography. Esophagogastroduodenoscopy and manometric tests. Splenoportography. Chest x-ray. Radiocardiogram. Cardiac and large vessel ultrasound.
• For drugs
  • Laboratory: liver function tests. Studies for hemolytic anemia (haptoglobins, lacticodehydrogenase 1-2, etc.).
  • Biopsy: liver.