Splenic physiology

The spleen



§   Site of haemopoiesis from the third month until birth

§   Bone marrow becomes a site of haemopoiesis from about 20 weeks becoming the dominant site of haemopoiesis around birth

§   Remains a potential site for haemopoiesis throughout life


Structure and Function

§        Normal length 8-13cm (>14cm usually palpable); weight 250g (can be up to 2kg)

§        5% cardiac output enters the spleen

§        Blood brought into the spleen via the splenic artery that then divides into the trabecular arteries which then branch into the central arteries, which are sited in the white pulp

§        The central arteries run in the central axis of the periarteriolar lymphatic sheaths

§        These give off many arterioles and capillaries some of which terminate in the white pulp whilst others enter the red pulp

§        Blood enters sinuses in the red pulp which are lined by endothelial cells and adventitial cells with a basement membrane

§        The sinuses are connected by cords (Bilroth cords) which consist of a fibroblast-like reticular meshwork containing numerous macrophages and erythrocytes.

§        A few arteries enter the sinuses directly and connect via the collecting vein to the trabecular system

§        Thus there is both rapid transit (1-2min) and slow transit (particularly when there is splenomegaly (30-60min – or longer)

§        Plasma skimming occurs by which the plasma and leukocytes pass preferentially into the white pulp while the red cells remain in the axial stream of the central artery

§        Passage of cells into the sinuses is assisted by the contraction of the reticular cells

§        Red cells that are inflexible or have inclusions remain in the cords and are either destroyed or conditioned for delayed transit

§        Spleen has 3 actions:

§        Sequestration – cells temporarily trapped by adhesion to the reticular meshwork of the cords on their passage th

§        Phagocytosis – irreversible uptake of damaged or antibody coated cells as well as particulate matter

§        Pooling

§        Increased amount of blood in the spleen in continuous exchange with the circulation

§        Since plasma passes freely through the spleen there is an increase in intrasplenic heamatocrit

§        The presence of metabolically active macrophages and densely packed red cells leads to reduced oxygen and glucose, which increased red cell rigidity

§        Siderotic granules, Howell-Jolly bodies, nuclear remnants and Heinz bodies are removed during temporary sequestration and the red cells are then returned to the circulation

§        Reticulocytes can be retained in the spleen for up to 3 days while they lose their intracellular inclusion bodies, alter the lipid composition of their membrane and reduce in size.

§        Antibody coated red cells loose pieces of their membrane becoming more spherical and less flexible each time they traverse the spleen.

§        It is not clear that the spleen has any special role in the removal of senescent red cells (more likely that the general reticuloendothelial system does this – especially the bone marrow).


Blood pooling

§   Normal red cell content of the spleen is around 70mL (5% of circulating red cells)

§   When the spleen enlarges up to 40% of the red cell mass may be pooled in the spleen

§   This functionally excludes a large volume of red cells from the circulation and results in functional anaemia (will give a falsely normal red cell mass result)

§   Important in myelofibrosis and hairy cell as well as portal hypertension

§   In splenomegaly due to cellular infiltration the pool is less prominent


Granulocyte pooling

§   30-50% of the bodies circulating granulocytes are stored in the spleen, with a mean transit time of around 10min

§   Neutropenia may occur with hypersplenism

§   Up to 40% of platelets are also pooled in the spleen and the pool increases when the spleen is enlarged


Immunological functions

§   White pulp is the largest single accumulation of lymphoid tissue in the body.

§   Contains 25% of T cells (in the periarteriolar sheaths) and 10% of B cells (in germinal centres in the white pulp)

§   During the primary immune response CD8+ T cells act in association with macrophages to stimulate removal by phagocytosis of blood-borne bacteria

§   Circulating immune complexes are removed by macrophage phagocytosis if they are large and B cells if they are small

§   These are important mechanisms for protection against N. meningitides, H. influenzae B, and strep pneumoniae

§   Also important in protection against viral infection and parasites such as plasmodium


Coagulation factors

§   Spleen can make VIII

§   Also functions as a reserve pool for platelets


Extramedullary haemopoiesis

Two possible circumstances when the spleen can regain haemopoiesis

1.      Severe anaemia as in chronic haemolysis, megaloblastic anaemia or thalassaemia

2.      Myelofibrosis and occasionally secondary carcinomatosis when there is myeloid metaplasia

Mechanism not entirely clear

§   Growth factors

§   Entrapment of circulating stem cells in the red pulp when they have escaped the bone marrow when the marrow expands (as in severe anaemia)


Causes of splenomegaly


§   Acute leukaemia

§   CML

§   CLL

§   Lymphoma

§   Myelofibrosis (chronic)

§   PV / ET

§   Hairy cell leukaemia

§   Gaucher’s disease, Niemann-Pick disease

§   Thalassaemia / Sickle cell / HbSC

§   Haemolytic anaemia

§   Megaloblastic anaemia



§   Viral (EBV, CMV, HIV)

§   Bacterial (TB, typhoid, SBE)

§   Parasitic (Malaria, leishmaniasis, schistosomiasis, trypanosomiasis)

§   Autoimmune (SLE, Rheumatoid)

§   Amyloidosis

§   Sarcoidosis



§   Portal hypertension

§   Cardiac failure

§   Splenic / portal / hepatic vein obstruction






Causes of hyposplenism

§        Ageing

§        Haematological

§        HbSS

§        Thombocythaemia

§        Myelofibrosis

§        Lymphomas

§        Infection

§        Malaria

§        Auto-immune disease

§        SLE, Rheumatoid, Sarcoid

§        Hyperthyroidism

§        GI

§        Gluten enteropathy (dermatitis herpetiformis), Crohn’s, Ulcerative colitis

§        Infiltration

§        Amyloid

§        Cysts (eg hydatid)

§        Nephrotic syndrome

§        Drugs (IVIg, corticosteroids, methyldopa)

§        Splenectomy / irradiation



Red cell changes

§   Howell-Jolly bodies

§   Siderotic granules

§   Reticulocytosis

§   Target cells

§   Contracted cells


Immunoglobulin production

§   IgM decreases post splenectomy

§   IgG remains normal

§   IgA and IgE increase


Asplenic patients



1.      All splenectomised/ hyposplenic patients should receive pneumococcal immunisation

2.      All not previously immunised should receive

a.      HIB

b.      Meningococcal C conjugate vaccine

3.      Influenza immunisation

4.      life-long antibiotics

5.      patients developing infection, must be admiited and given systemic antibiotics

6.      patients should be given written information and carry a health card to alert health professionals of risk of overwhelming infection

7.      patient education , esp to risks of overseas travel incl malaria




§        Live vaccines can be safely given

§        Pneumococcal vaccination

§        Polyvalent

§        High degree of immunity in normal subjects

§        Documented failures in hyposplenic patients

§        Break through infection may occur

§        Children <2years have a reduced ability to mount an antibody response to polysaccharide antigens, and therefore are at particular risk of vaccine failure

§        a conjugate vaccine provides a more reliable serological response

§        Conjugate seven valent vaccine

§        More immunogenic

§        More limited repertoire in terms of sero-types

§        Timing

§        At least 2 weeks before splenectomy

§        If after, functional antibody responses are better with delayed (14 days) vaccination

§        Delay until 3 months after immunosuppressive chemotherapy or radiotherapy

§        Re-immunisation is recommended every 5 years

§        Antibody levels may decline more quickly especially in patients with SCD or LPD

§        Decisions on reimmunisation may be made on basis of antibody levels

§        Haemophilus influenzae B

§        No data to support reimmunisation

§        Meningococcal

§        Group A rare in UK (<2%)

§        Epidemic in other areas of the world

§        Group B 60%

§        Group C 40%

§        Meningococcal C conjugate vaccine

§        Part of routine childhood immunisation

§        Immunogenic even in children <2 years

§        3 doses to infants and 2 doses to previously non-immunised children between 4-12 months of age

§        In non-immunised older children/ adults a single dose is recommended

§        Should be given pre-splenectomy if not already had

§        Travellers should also receive a vaccine which protects against strain A

§        Meningococcal plain polysaccharide A and C vaccine

§        Protection is short lived

§        Hyposplenic individuals who have received this, should also receive meningococcal C conjugate vaccine

§        Influenza

§        Annual vaccine recommended


§        Antibiotic prophylaxis

§        Life long antibiotics recommended

§        Very little pneumococcal resistance to penicillin in the UK