5. Haemopoeisis, Spleen And Bone Marrow Flashcards
Where does the production of blood cells occur?
Bone marrow
In adult: pelvis, sternum, skull, ribs, vertebrae
In infant: extensive throughout skeleton
What is differentiation of haemopoietic stem cells determined by?
Hormones
Transcription factors
Interactions with non-haemopoietic cell types
What is the role of erythropoietin?
Secreted by kidney and stimulates red blood cell production
What is the role of thrombopoietin?
Produced by liver and kidney and regulates production of platelets
What are the 2 progenitor cell types?
Common myeloid
Common lymphoid
What do common myeloid progenitors differentiate into?
Megakaryocytes (platelets)
Erythrocytes
Myeloblasts
What do myeloblasts differentiate into?
Basophils
Neutrophils
Eosinophils
Monocytes -> macrophage
What do common lymphoid progenitors differentiate into?
Small lymphocytes
What do small lymphocytes differentiate into?
B lymphocytes
T lymphocytes
What are the features of haemopoietic stem cells?
Capable of self-renewal
Given appropriate stimuli can differentiate into variety of specialised cells
What is extramedullary haematopoiesis?
In pathological conditions such as myelofibrosis or thalassaemia haemopoietic stem ells can mobilise into circulating blood to colonise other tissues
What is the reticuloendothelial system (RES)?
Part of immune system and made up of monocytes in blood and a network of tissues which contain phagocytic cells
What is the role of the RES?
To remove dead or damaged cells and identify and destroy foreign antigens in blood and tissues
What are the main organs of the RES?
Spleen and liver
RES cells in spleen dispose of blood cells
What are the functions of the spleen in adults?
Sequestration and phagocytosis
Blood pooling (platelets and RBC can be rapidly mobilised during bleeding)
Extramedullary haemopoeisis
Immunological function
What can cause splenomegaly?
Back pressure - portal hypertension in liver disease
Over work (red or white pulp)
Extramedullary haemopoeisis
Expanding as infiltrated by cells (cancer)
Expanding as infiltrated by other material
What is hypersplenism?
Low blood counts occur due to pooling of blood in enlarged spleen
What is hyposplenism?
Lack of functioning splenic tissue
What can cause hyposplenism?
Splenectomy
Sickle cell disease
Gastrointestinal diseases (coeliac, Crohns, ulcerative colitis)
Autoimmune diseases (systemic lupus, rheumatoid arthritis)
What are Howell Jolly bodies?
RBC with DNA remnants - normally removed by spleen
What are patients with hyposplenism at risk of?
Sepsis from encapsulated bacteria
E.g. streptococcus pneumonia, haemophilus influenzae, meningococcus
Patients must be immunised and given life long antibiotic prophylaxis
What happens when there are changes to the RBC plasma membrane?
Causes cell to become less derformable and more fragile
What proteins are involved in hereditary spherocytosis?
Spectrin
Ankyrin
Band 3
Protein 4.2
What is spectrin?
Actin crosslinking and molecular scaffold protein that links plasma membrane to actin cytoskeleton
What is ankyrin?
Links integral membrane proteins to the underlying spectrin-actin cytoskeleton
What is band 3 protein?
Facilitates chloride and bicarbonate exchange across membrane and also involve in physical linkage of membrane to cytoskeleton (binds wit ankyrin and protein 4.2?
What is protein 4.2?
ATP-binding protein which may regulate the association of band 3 with ankyrin
Describe the degradation of haem
Senescent RBC engulfed by macrophage in reticuloendothelial system
Haem is recycled as Fe2+ or converted to bilirubin
Unconjugated bilirubin transported in blood bound to albumin
Some bilirubin taken up by liver ad conjugated with glucuronic acid
Conjugated bilirubin secreted in bile into duodenum
Either into faeces or reabsorbed and excreted in urine
What is the conjugated form of bilirubin?
Bilirubin diglucoronide
What form of bilirubin is in faeces?
Stercobilin
What form of bilirubin is in urine?
Urobilin
What is cytopenia?
A reduction in the number of blood cells
What does …cytosis or …philia at the end of a word mean?
An increase in the number of blood cells
What are neutrophils?
First-responder phagocyte
Most common white cel
Essential part of innate immune system
Circulate in bloodstream and invade tissues (lifespan 1-4 days)
What is the maturation of neutrophils controlled by?
The hormone G-CSF, a glycoproteins growth factor and cytokine
What does G-CSF do?
Increases production of neutrophils
Speeds up releas of mature cells from BM
Enhances chemotaxis
Enhances phagocytosis and killing of pathogens
When is recombinant G-CSF administered?
When more neutrophils are needed
E.g. a patient with severe neutropenia and sepsis after chemotherapy
What is neutrophilia?
An increase in the absolute number of circulating neutrophils
What can cause neutrophilia?
Infection Tissue damage Smoking Myeloproliferative diseases Cancer Acute haemorrhage
How does acute haemorrhage cause neutrophilia?
Neutrophils usually stick to endothelial cells of vessels
These are released in haemorrhage increasing the number of circulating neutrophils
What are the consequences of neutropenia?
Severe life threatening bacterial infection
Severe life threatening fungal infection
Mucosal ulceration
What causes reduced production of neutrophils and therefore neutropenia?
B12/folate deficiency Aplastic anaemia Viral infection Congential Drugs Radiation
What causes increased removal or use of neutrophils and therefore neutropenia?
Immune destruction
Sepsis
Splenic pooling
What are the features of monocytes?
Largest cells in blood
In tissues differentiate into macrophages or dendritic cells
Phagocytose microorganism and breakdown/remove cellular debris
Antigen presenting role to lymphocytes
Defence against chronic bacterial infections
What are the causes of monocytosis?
Bacterial infection
Inflammatory conditions
Carcinoma
Myeloproliferative disorders and leukaemias
What are the features of eosinophils?
Responsible for immune response against multicellular parasites
Mediator of allergic responses
Granules contain array of cytotoxic proteins
Phagocytosis of antigen-antibody complexes
What are the common causes of eosinophilia?
Allergic diseases
Parasitic infection
Drug hypersensitivity
Skin diseases
What are basophils?
Large dense granules containing histamine, heparin, hyaluronic acid, serotonin
Granules stain deep blue
Active in allergic reactions and inflammatory conditions
What are the 3 types of lymphocytes?
Bc ells
T cells
Natural killer cells
What can cause lymphocytosis?
Viral infections Bacterial infections Stress related: MI/cardiac arrest Post splenectomy Smoking Leukaemia Lymphoma
