5- Haemopoiesis, Spleen & Bone Marrow

Question 1

• define haemopoiesis, give the distribution of it in the body
• describe haematopoetic stem cells and give some sources of them.
• how is a bone marrow sample obtained?
• name the main 5 blood cell groups and give the growth factors for each.

Answer 1

• production of blood cells in the bone marrow from haematopoetic stem cells (HPSCs), more in midline of body ie skull ribs, spine, pelvis, NOT in long bones
• these are capable of self renewal, can differentiate, in disease states they can mobilise into circulating blood to colonise other tissues (called extramedullary haematopoeisis). Found in bone marrow, peripheral blood stem cells, umbilical cord.
• trephine biopsy into spongy bone
• 1)erythrocytes =erythropoietin secreted by kidney, 2) Lymphocytes= interleukins, 3)Granulocytes (neutrophils, eosinophils, basophils)= G-CSF, 4)monocytes, 5)platelets= thrombopoietin

Question 2

• what is the reticuloendothelial system? What are the main organs and what is its function?
• functions of the spleen in adults?
• how does blood flow to the spleen?
• what causes splenomegaly and where is it felt on examination? What’s the risks?

Answer 2

• part of the immune system, made up of monocytes in blood and a network of tissues containing macrophages eg in skin= langerhans, in cns=microglia
• main role is to remove dead or damaged cells and identify & destroy foreign antigens, dispose of old blood cells, main organs are liver and spleen (red pulp-sinuses are lines w endothelial macrophages, white pulp-similar to lymph follicles)
• F= sequestration and phagocytosis of old erythrocytes >120 days old, blood pooling platelets and RBCs rapidly used if there’s a bleed, extramedullary haematopoeisis (when spleen takes over bone marrow duties), immune functions
• blood flows to the spleen via the splenic artery.
• splenomegaly bc portal hypertension in liver disease, overworked red or white pulp, extramedullary haematopoeisis, expansion during huge infection as WBCs pool in white pulp, patient breathes in and can feel spleen moving towards hand at right iliac fossa.
• high risk of rupture, low blood counts in body as blood is pooled at spleen.

Question 3

• what is hyposplenism, name some causes, what is a huge risk for patients?
• describe the structure of erythrocytes and give their functions.
• what is the structure of the red blood cell membrane?
• explain how haem is degraded and how this could lead to jaundice.

Answer 3

• lack of functioning spleen, could be due to a splenectomy ie removal, sickle cell disease, some GI diseases, some autoimmune disorders. Patients are at high risk of encapsulated bacteria (thiccer cell wall) therefore should be immunised to prevent serious infection eg strep pneumoniae, meningococcus.
• biconcave cells containing Hb, 4 globin chains, each w a haem group, exists as HbO2 or deO2 Hb
• RBC membrane= contains 4 proteins, 1)spectrin=peripheral, links pm to actin cytoskeleton 2)ankyrin=peripheral, links integral proteins to the spectrin-actin cytoskeleton 3)band 3=integral, facilitates Cl- and HCO3- exchange across membrane, also physically links membrane to cytoskeleton 4)protein 4.2= ATP binding protein regulated ass. of band 3 w ankyrin. Changes to plasma membrane deform cells and make them more fragile, spleen removes these ‘abnormal’ cells and haemolytic anaemia can result
• old aged erythrocytes are engulfed by macrophages in reticuloendothelial system, the haem group is removed and Fe2+ is recycled, unconjugated bilirubin forms, travels to liver, becomes conjugated w glucuronic acid, secretes in bile into SI, bacteria remove the glucuronic acid and the bilirubin is converted to urobilinogen which is oxidised to a substance that colours faeces, and a substance that colours urine. Problem arises when there is excess unconjugated bilirubin in blood bc liver is overwhelmed(haemolytic anaemia) or not working and colours sclera and skin yellow jaundice

Question 4

What do the terms -cytosis and -philia mean? Define cytopenia

• what are neutrophils? What is recombinant g-csf used for? What causes neutrophilia?
• what causes neutropenia and what are some consequences?
• what are monocytes and what are some causes of monocytosis

Answer 4

• they mean an increase in number of blood cells, cytopenia= reduction in number of blood cells
• first responder phagocyte, most common WBC, essential in innate IS, invade tissues, matured by G-CSF which enhances chemotaxis and phagocytosis
• it’s given when more neutrophils are needed eg a patient is undergoing chemotherapy
• neutrophilia= increased neutrophils, due to infection, tissue damage, myeloproliferative diseases
• neutropenia=decrease in circulating neutrophils, severe bacterial infection, neutropenic sepsis, B12/folate deficiency so insufficient DNA synthesis, drugs like chemo
• monocytes are the largest cells in blood, circulate for 1-3 days before differentiating into macrophages or dendritic cells, APCs, important for chronic bacterial infections eg TB. Causes of monocytosis= chronic bacterial infection, inflammatory conditions eg UC, leukaemias

Question 5

• what are eosinophils? Give causes of eosinophilia.
• what are basophils? Give causes of basophilia
• what are lymphocytes? Give causes of lymphocytosis.

Answer 5

• lifespan of 8-12 days, immune response against parasites, mediate allergic responses, inappropriate activation is responsible for tissue damage eg asthma. Eosinophilia= allergic reactions, parasitic infection, skin diseases, hodgkins lymphoma
• basophils=least common, large, rarely seen, active in allergic and inflammatory conditions, dense granules containing histamines. Basophilia= caused by immediate hypersensitivity reactions, ulcerative colitis, myeloproliferative reactions
• lymphocytes= originate in bone marrow, B cells made to order, form plasma cells then antibodies, T cells then travel to thymus to mature, CD8+ (MHC 1) and CD4+ (MHC 2), NK cells, Lymphocytosis= viral infections, bacterial infections, leukaemia, lymphoma.