THE SPLENOMEGALY

The splenomegaly is a quite common finding in acute or chronic illnesses. It is rarely isolated, in most cases being accompanied by hepatomegaly, the hepatosplenomegalic syndrome, in which, either spleen or liver enlargement may be most evident.

 Structure of the spleen. The spleen is a parenchymal organ, situated in the left hypocondrium. The spleen weights about 200g and is enveloped by a fibrous capsule, which is the origin for fibrous extension ( Sept ) that divide the organ into several lobules. The functional tissue has two divisions : -the white pulp, organised in lymph nodes ( Malpyghis corpuscles ) and lymphoid sheaths that that surround the small arteries. The spleen corpuscles contain type B lymphocytes the thymus dependent zone, while the lymphoid sheaths contain type T lymphocytes the independent zone. -the red pulp is situated among the lymphoid structures and it consists of spleen sinuses and spelling cords ( the Billroths cords ) suspended in a reticulo-histiocitar tissue.

 The functions of the spleen should be understood in terms of the cumulated functions of the reticulo-histiocitar system and the lymphatic system. In addition, the spleen has a tight relationship with the other two important conglomerations of the reticulo-histiocitar system : the liver and the bone marrow, a continuous neuro-hormonal communication taking place between them. Originality of the spleen consists of its unique vascular system, made of capillaries and sinuses with discontinuous walls, that have the capacity of a filter. The situation of the spleen between the systemic and portal blood circulation, and its capacity to increase its volume explain the important role the spleen plays in the hemodynamic regulation of these territories.

 The spleen has several functions : 1). The hemodynamic function : a).Storage site for the blood : of small importance in the healthy individual, it becomes important in case of hypertrophy when up to 20% of the total erythrocytes can be stored inside the spleen. Although hemolysis does not occur to a big extent in this pool, a prolonged sequestration may lead to a brittleness of the erythrocyte walls even in normal cells. During a loss of blood or a hypoxic state, the spleen is able to contract in order to release erythrocytes, leukocytes and platelets in the circulating blood.

b).Being an extensible vascular sponge connected with the portal circulation, the spleen regulates the level of the portal pressure, thus preventing the acute portal hypertension and the tendency to haemorrhages.

 2). Haematological functions: a).Site of hematopoyesis: -Through the red pulp it produces and releases monocites. -Through the white pulp it produces lymphocytes and plasma cells. During the intrauterine period the spleen plays an important role in hematopoyesis. This situation ends at birth, but may pathologically reappear as extramedulary hematopoyesis in haemolytic anaemia, Rh incompatibility or chronic myeloid leukaemia. b).Site for hemolysis: nowadays the spleen is not seen as a cemetery for old red cells any more. Normal hemolysis takes place 50% in bone marrow and 50% in the liver and spleen (25% each). The spleen seems to play a role in controlling the finishing of the erythrocytes, thats probably why in the spleen agenesy or after splenectomy, various abnormalities of the erythrocytes are found: the Jolly corpuscles (nuclear remains), siderocytes (erythrocytes containing hemosiderine granules), Heinzs corpuscles (degraded Hb), etc.

c).The spleen and the Platelets: after about 10 days in circulation, the thrombocytes are destroyed inside the spleen. The spleen normally contains one third of the total platelets, but this proportion may increase up to 90% during a hypersplenic state. That explains why after splenectomy an increased platelet number is found in the circulating blood. d).The spleen and blood clotting: -Storage of platelets and of the VIII clotting factor -Clearance of the tromboplastine and fibrin complexes

 3). The spleen and the Immune Defences: The spleens role in immunity is proved by the increased vulnerability to infections during the first year after splenectomy or after splenectomy performed under 5 years of age. a)Fagocytosis: is based on the spleens richness in R-H tissue. The spleen phagocytes are the endothelial cells from the walls of the sinuses and the reticular cells from the Billroths cords, either fixed or mobile. Thus, the spleen tissue becomes a filter able to filtrate bacteria, parasites, cancerous cells, abnormal erythrocytes, colloidal and lipidic substances. It seems that during the first month of life the spleen R-H tissue is likely to be only tissue able to fagocitate foreign particles, since no natural antibodies is yet present.

 b).Production of Antibodies: the spleen is a lymphoid organ. The spleen, like the lymph nodes, are the peripheral lymphoid tissue. Since the spleen is located on the blood circulation, while the lymph nodes are located on the lymph circulation, a difference in quality and quantity in their immune functions is found. -Quantity: the spleen permanently contains a big amount of lymphocites. The lymphopenia found after radiation of the spleen is more important than the one found after drainage of the thoracic duct. -Quality: the spleen does not have afferent lymphatic vessels, so it can be stimulated only by circulating antigens.

 The humoral response may be primary (IgM production) or secondary (IgG production). The increased vulnerability to infections after splenectomy (more evident in children as in adult individuals) may be explained by the long lasting alterations of the primary response to intravenous immunization, by the decreased IgM level during the first 6 month after splenectomy, and also by the loss of an important fagocitating organ. 4). The metabolic functions of the spleen. The spleen participates to the metabolism of water, calcium, potasium, lipides and proteins.

The hypersplenism is a controversial issue. For its understanding several hypotheses are discussed: a).Hyperplasia of histiocitar cells with an increased capability of fagocitation; b).The presence of a spleen hormone which may inhibit the bone-marrow cell production and maturation, leading to medular aplasia. c).Spleen production of specific antibodies directed against blood cells and bone-marrow hematopoyetic cells. In this way, these cells become more fragile and can be retained and destroyed in the spleen much easier. This explanation seems to be the most accepted one. The hypersplenic syndrome associates: -anaemia, neutropenia, thrombocitopenia, isolated or associated; the reticulocyte number is variable; -normal or hypercellular aspects of the bone marrow; -splenomegaly; -the blood formula comes back to normal after splenectomy.

 EXPLORATION OF THE SPLEEN Clinical findings: - Inspection: only a huge spleen enlargement is able to swell the left hemithorax, the left hypocondrium and the middle abdomen; - Palpation is the most important exam. It can be performed either with the patient laying on his back or laying on his right side. Are to be apreciated:sensibility -consistency :-hard: sarcomas, leukemias -soft : infectious disease -surface: normally smooth having front edge winding, may become irregular in tumors, leukemias, hydatidosis -mobility: the spleen normally lowers with inspiration. In newborn and small child, the normal spleen is palpable in up to 10% of the cases.

 Hackett states five degrees of spleen enlargement (accepted by WHO): 1st degree: palpable spleen during a profound inspiration; 2nd degre: the spleen does not pass below a horizontal line drawn at half distance between the umbilicus and the lowest rib edge; 3rd degree: the spleen passes below this line; 4th degree: between the umbilicus and the horizontal line drawn at half distance between the umbilicus and the pubis; 5th degree: it passes below this last line. - Percussion: not suitable for children; - Hearing: a vascular noise may be heard in case of aneurism of one of the spleen arteries;

 The splenomegaly is to be differenciated from: 1.Chest or abdominal walls tumours (such tumours move along with the wall during contraction; 2.A hypertrophic left lobe of the liver; 3.Left kidney hydronephrosis or tumour; 4.Adrenal gland tumour; 5.Tumour of the stomach, of the colon; 6.End of pancreas tumour; 7.Mezentheric tumour; 8.Gigant ovarian tumour.

Laboratory findings: 1.Hematologic findings: .erythrocyte counting .leukocyte counting and formula .thrombocyte counting .reticulocyte . Globular osmotic resistance of erythrocites . Electroforesis of Hb . The bone marrow aspect and cellularity . The bilirubin levels: either free or combined . The seric iron level . Erythrocytar G6PD level 2.Blood culture 3.The serology of the blood 4.Hepatic tests 5.Intradermoreactions with tuberculin and other antigenes

 6.Radiology findings: . simple radiography or after insuflation of air in the perithoneal cavity . splenoportography . selective arteriography 7.Ultrasonography 8.CT scan 9.MRI 10.Puncture of the spleen: it normally contains: Ly=60-80% H=20-30% G=10% 11.Limph node, liver and marrow puncture or biopsy 12.Scintigraphy-with radioactive gold 198 -after introduction in circulation of E marqued with radioactive 51 chromium

 Splenomegaly may be: - isolated - associated with: - hepatomegaly - fever - adenomegaly - hematological disorders

Differential Diagnosis of Splenomegaly by Pathophysiology after Susan B. Shurin and Kelly W. Maloney I. Anatomic lesions: - Cysts, pseudocysts - Hemangiomas and lymphangiomas - Hematoma or rupture ( traumatic ) II. Hyperplasia caused by Hematologic Disorders a) Acute and Chronic Hemolysis - Hemoglobinopathies - Erythrocyte membrane disorders - Erythrocyte enzyme deficiences - Immune hemolysis - Paroxysmal nocturnal hemoglobinuria

b) Chronic Iron Deficiency

c) Extramedullary Hematopoiesis - Severe hemolytic anemias - Myeloproliferative diseases: chronic myelogenous leukemia ( CML ), juvenile CML, myelofibrosis with myeloid metaplasia, polycythemia vera - Osteopetrosis

 III. Infections
a) Bacterial - Acute sepsis: Salmonella typhi, Streptoccocus pneumoniae, Haemophilus infl. Type b, Staphyloccocus aureus. - Chronic infections: infective endocarditis, chronic meningococcemia, brucellosis, tularemia, cat-scratch disease - Local infections: splenic abscess, pyogenic liver abscess, cholangitis

b) Viral - Acute viral infections, especially in children - Congenital cytomegalovirus ( CMV ), herpes simplex, rubella - Hepatitis A, B, and C; CMV - Epstein-Barr virus - Psittacosis - Human immunodeficiency virus ( HIV )

c) Spirochetal - Syphilis, especially congenital syphilis - Lyme disease - Leptospirosis d) Rickettsial - Q fever - Typhus e) Fungal / Mycobacterial - Miliary tuberculosis - Disseminated histoplasmosis - Systemic candidiasis ( in immunosuppressed patients )

 f) Parasitic - Malaria - Toxoplasmosis, especially congenital - Toxocara canis, toxocara cati ( Visceral larva migrans ) - Leishmaniasis ( Kala-Azar ) - Schistosomiasis - Trypanosomias - Fascioliasis

 IV. Immunologic and Inflammatory Processes - Colagen vascular diseases - Systemic lupus erythematosus - Rheumatoid arthritis - Mixed connective tissue disease - Systemic vasculitis - Serum sickness - Drug hypersensitivity, especially to phenytoin - Sjgren syndrome - Cryoglobulinemia

- Amyloidosis - Inflammatory bowel disease - Myasthenia gravis - Sarcoidosis - Histiocytosis syndromes - Graves disease - Hashimoto thyroiditis

 V. Malignancies a) Primary - leukemia ( acute, chronic ) - lymphoma - angiosarcoma - Hodgkin disease b) Metastatic

 VI. Storage Diseases - Lipidosis ( Gaucher disease, Niemann-Pick disease ) - Mucopolysaccharidoses ( Hurler, Huntertype ) - Mucolipidosis - Defects in carbohydrate metabolism ( galactosemia, fructose intolerance ) - Sea-blue histiocyte syndrome - Amyloidosis

 VII. Congestive - Congestive heart failure - Intrahepatic cirrhosis - Extrahepatic portal splenic, and hepatic vein obstruction ( thrombosis, Budd-Chiari syndrome ).