S3 Haemopoiesis, the Spleen and Bone Marrow Flashcards
Where does production of blood cells occur? What is the bone marrow distribution in adults and infants?
In the bone marrow
Adults - limited distribution (pelvis, sternum, skull, ribs, vertebrae)
Infants - extensive distribution throughout skeleton
What is differentiation of haemopoietic stem cells determined by?
- hormones - erythropoietin and thrombopoietin
- transcription factors
- interactions with non-haemopoietic cell types e.g. endothelial cells
Where is erythropoietin secreted? What does it stimulate?
In the kidneys
RBC production
Where is thrombopoietin produced? What does it regulate?
The liver and kidney
Production of platelets
What are haemopoietic stem cells (HPSCs) able to do more than other adult tissue?
Self-renew
What are the sources of haemopoietic stem cells (HPSCs)?
- bone marrow aspiration
- GCSF mobilised peripheral blood stem cells, collected by leucopharesis
- umbilical cord stem cells, “cord bank”
What is the reticuloendothelial system (RES)? What is it made up of? Where does it mainly occur?
It is part of the immune system.
Made up of monocytes in the blood and a network of tissues that contain phagocytic cells.
Mainly in the spleen and liver
What tissues are each, Kupffer cell, tissue histiocyte, microglia, peritoneal macrophage, red pulp macrophage, Langerhans cell, found in?
- Kupffer cell - liver
- tissue histiocyte - connective tissue
- microglia - central nervous system
- peritoneal macrophage - peritoneal cavity
- red pulp macrophage - spleen
- Langerhans cell - skin and mucosa
What is the role of macrophages?
To remove dead/damaged cells and identify and destroy foreign antigens in blood and tissues
What do RES cells in the spleen do?
Dispose of blood cells, e.g. damaged/old RBCs
Describe the structure of the red pulp in the spleen.
Contains sinuses (vessels/tracts) lined by endothelial macrophages and cords
Describe the structure of the white pulp in the spleen.
Has a similar structure to lymphoid follicles
What is the function of the spleen in adults?
- sequestration and phagocytosis
- blood pooling
- extramedullary haemopoiesis
- immunological function
What is blood pooling?
Platelets and RBCs can be rapidly mobilised during bleeding
What is extramedullary haemopoiesis?
Haemopoiesis happening outside the bone marrow e.g. in the spleen.
Pluripotent stem cells proliferate during haematological stress/if bone marrow fails
What is myelofibrosis?
Bone marrow cancer that leads to scarring of the bone marrow
What % of T and B cells are present in the spleen?
T cells - 25%
B cells - 15%
How does blood enter the spleen?
Splenic artery
What is splenomegaly?
Spleen enlargement
Why would splenomegaly occur?
- red or white pulp being over worked
- back pressure from the hepatic portal system (portal hypertension in liver disease)
- extramedullary haemopoiesis
- expanding as cells infiltrate e.g. cancer cells or blood origin or cancer metastases
- expanding as materials infiltrate
What is hypersplenism?
Low blood counts can occur due to pooling of blood in enlarged spleen
Why should you avoid contact sports and vigorous activity if you have an enlarged spleen?
To avoid the risk of rupture as it is no longer protected by the rib cage
What are some major causes of splenomegaly?
- chronic myeloid leukaemia
- myelofibrosis
- malaria
- schistosomiasis
What are some moderate causes of splenomegaly?
- lymphoma
- leukaemias
- myeloproliferative disorders
- liver cirrhosis and portal hypertension
- infections e.g. glandular fever
What are some mild causes of splenomegaly?
- infectious hepatitis
- endocarditis
- infiltrative disorders e.g. sarcoidosis
- autoimmune diseases e.g. AIHA
How do you feel for an enlarged spleen?
Never normal for the spleen to be palpable below the costal margin
- Start to palpate in the right iliac fossa (RIF)
- Feel fo spleen edge moving towards your hand on inspiration
- Feel for the splenic notch
- Measure in cm from the costal margin to midclavicular line
What is hyposplenism?
Lack of functioning splenic tissue
What are some causes of hyposplenism?
- splenectomy
- sickle cell disease
- gastrointestinal diseases e.g. coeliacs, crohn’s and ulcerative colitis
- autoimmune disorders e.g. systemic lupus, rheumatoid arthritis, hashimoto’s disease
What are Howell Jolly bodies?
DNA remnants in RBCs
Seen on a blood film, usually removed by spleen so appearance of them is a sign of hyposplenism
What are patients with hyposplenism at risk of?
Sepsis from encapsulated bacteria e.g. streptococcus pneumonia, haemophilus influenzae and meningococcus
What do you give the patients with hyposplenism?
Life long antibiotic prophylaxis immunisations
When does fetal Hb switch to adult Hb
About 3-6 months of age
What are the membrane proteins of a RBC?
- spectrin (peripheral)
- ankyrin (peripheral)
- band 3 (integral)
- protein 4.2 (peripheral)
What organ recognises changes in RBC shape/membrane structure? What does it do? To prevent what?
The spleen - it removes them from circulation to prevent haemolytic anaemia occurring
What does spectrin do?
It links the plasma membrane to the actin cytoskeleton
What does ankyrin do?
Links integral membrane proteins to the underlying spectrin-actin cytoskeleton
What does band 3 do?
Facilitates chloride and bicarbonate exchange across the membrane and involved in the physical linkage of the membrane to the cytoskeleton (binds to ankyrin an protein 4.2)
What does protein 4.2 do?
An ATP-binding protein that may regulate the association of band 3 with ankyrin
What is cytopenia?
Reduction in the number of blood cells
What is …cytosis or …philia?
An increase in the number of blood cells
What happens when haem is degraded?
- Senescent RBC engulfed by macrophages in the RES
- Haem released, Fe2+ is recycled
- Haem breaks down into bilirubin which is transported in blood bound to albumin
- Bilirubin is conjugated with glucuronic acid and is secreted in the bile where it is removed via the faeces or urine
- If there is excess bilirubin in the blood, jaundice occurs
What do you call an increase and decrease in RBCs?
Increase - polycythaemia or erythrocytosis
Decrease - anaemia
What do you call an increase and decrease in WBCs?
Increase - leucocytosis
Decrease - leucopenia
What do you call an increase and decrease in lymphocytes?
Increase - lymphocytosis
Decrease - lymphocytopenia
What do you call an increase and decrease in monocytes?
Increase - monocytosis
Decrease - monocytopenia
What do you call an increase and decrease in neutrophils?
Increase - neutrophilia
Decrease - neutropenia
What do you call an increase and decrease in eosinophils?
Increase - eosinophilia
Decrease - eosinopenia/low eosinophils count
What do you call an increase and decrease in basophils?
Increase - basophilia
Decrease - basopenia/low basophil count
What do you call an increase and decrease in platelets?
Increase - thrombocytosis/thrombocythaemia
Decrease - thrombocytopenia
What do you call an increase and decrease in all blood cell types?
Increase - panmyelosis
Decrease - pancytopenia
What controls the maturation of neutrophils?
G-CSF
What part of the immune system are neutrophils part of, innate or adaptive?
Innate
How long to neutrophils live for?
1 to 4 days
What does G-CSF control?
- neutrophil production
- chemotaxis
- phagocytosis and killing of pathogens
What is neutrophilia?
An increase in the absolute number of circulating neutrophils
What causes neutrophilia?
- infection (most common)
- tissue damage
- smoking
- drugs e.g. steroids
- myeloproliferative diseases (rare)
- cytokines (G-CSF)
- cancer
What can cause neutropenia?
- reduced production - B12/folate deficiency, aplastic anaemia, radiation, drugs, viral infection, congenital
- increased removal/use - immune destruction (autoantibodies), sepsis, splenic pooling
What are the consequences of neutropenia?
- severe life threatening bacterial infection
- severe life threatening fungal infection
- mucosal ulceration
How long do monocytes circulate fro before migrating to tissues to differentiate into macrophages/dendritic cells?
About 1 to 3 days
What are some causes of monocytosis?
- bacterial infection e.g. TB
- inflammatory conditions e.g. rheumatoid arthritis
- carcinoma
What can cause eosinophilia?
- common - allergic diseases, parasitic infection, drug hypersensitivity, skin diseases
- rare - Hodgkin lymphoma, acute lymphoblastic leukaemia, acute myeloid leukaemia, eosinophilic leukaemia
What do eosinophils do?
Responsible for immune response against multicellular parasites like helminths
Mediator of allergic responses
Phagocytosis of antigen-antibody complexes
When are basophils active?
(Least common)
Active in allergic reactions and inflammatory conditions e.g rheumatoid arthritis, hypersensitivity reactions and ulcerative colitis
Where do lymphocytes originate from?
Bone marrow
What rate the 3 types of lymphocytes?
B cells, T cells and natural killer cells
What type of immunity, humoral and cellular, are B and T cells involved in?
B cells - humoral
T cells - cellular
What are some causes of lymphocytosis?
- viral infections
- bacterial infections e.g. whooping cough
- post splenectomy
- smoking
- T-/NK- cell leukaemia
- lymphoma
