Normal Haematopoiesis Flashcards
What are the sites of haematopoiesis in humans?
Yolk sac
Liver and spleen
Bone marrow (in adults this is the central skeleton, proximal ends of femur).
What part of the bone marrow creates red blood cells
Red bone marrow
When do we find stem cells?
Bone marrow
what can stem cells develop into?
Red cells
White cells
Platelets
Multipotent haematopoitic stem cells can differentiate into what 2 types of cells?
Common myeloid progenitor and common lymphiod progenitor
What cells can the common myeloid progenitor differentaite into?
Erythrocytes, mast cells, myeloblasts, megokaryocytes
What can myeloblasts divide into?
Basophil, neutrophil, eosinophil, monocyte.
Where do macrophages come from?
Monocytes
What can lymphoid progenitors divide into?
Natural killer cells and small lymphocytes
What are the subcategories of small lymphocytes?
T-lymphocytes and B lymphocytes
Where do plasma cells develop from?
B lymphocytes
What can totipotent stem cells give rise to?
Intraembryonic and extraembryonic structures
Are stem cells capable of self renewal?
Yes
How do stem cells become self renewal?
They give rise to two daughter cells, one will stay as a stem cell the other will differentiation intp a specialised cells
How would you diagnose abnormalities in the blood?
Bone marrow examinations
Do blood cells become more or less identifiable as they develop?
More
Why dont red blood cells have nuclei?
They need more room to carry haemoglobin and oxygen around the body
Do HSC’s create niches and if so why?
Yes because they need to survive, it also helps them differentiate
How do cells make a niche?
Through extrinsic and intrinsic signalling pathways
Examples of the extrinsic signalling used to make a niche (what do growth factors help with?)
Growth factors which help cell survival, proliferation, differentiation, maturation and activation
Examples of the extrinsic signalling used to make a niche (what do adhesion molecules help with?)
Interactions with the extracellular matrix.
What are examples of intrinsic signalling to help with differentiation?
transcription factors
Growth factors can help create specifical lineages, for example what growth factor regulates erythropoiesis?
Renal erythropoietin which is stimulated by tissue oxygen
What growth factors encourage white cell growth (myelopoiesis) for granulocytes, macrophages and eosinophils?
Granulocytes = G-CSF
Macrophages - M-CSF
Eosinophils - IL-5
What growth factor encourages platelet differentiation (thrombopoiesis) and is part fo the feedback method to control platelet count?
Thrombopoietin from the liver
What does the normal peripheral blood (full blood count) tell you?
Gives you different values of peripheral blood. This includes, haemoglobin, RBC, Haematocrit (amount of blood which is actually cells), MCV, reticulocyte (immature cells), neutrophils, lymphocytes, eosinophils, monocytes, basophils and platelets
What conditions could arise from having too many of a type of cells?
Erythrocytosis - too many red cells
Leucocytosis - too many white cells
Thrombocytosis - too many platelets
All end in cytosis
What conditions could arise from having too little of a type of cells?
Anaemia - too little red blood cells
Leucopenia - too little white blood cells
Thrombocytopenia - too little platelets
Pancytopenia - too little of everything
All end in cytopenia (apart from anaemia)
Can cytosis and cytopenias be caused by malignancys and non-malignant diseases?
yes
Why is pancytopenia common in malignant disease?
The malignancy invades the entirety of the bone marrow pushing all the blood cells into the peripheral blood
What are myeloproliferative disorders?
These are too many cells caused by a malignancy
What can cause benign erythrocytosis?
Smoking, alcohol, altitude, lung disease
What can cause benign leucocytosis?
Infection, inflammation
What can cause benign thrombocytosis?
Iron deficiency, infection
What are some ways to can get cytopenias?
This is a failure of production which can be inhertied or acquired, general or specific, primary (primary bone marrow disorder) or secondary (e.g infection is worse, sepsis).
what causes cytopenias?
Excessive loss or consumption of cells. For example a massive bleed or a an autoimmune consumption (the body is attacking its own cells).
Does anaemia cause less oxygen to be in the body?
Yes
Symptoms of anaemia?
Lethargy, breathlessness, chest pain, headache, dizziness, pallor.
Can some people function with very low haemoglobin levels?
Yes if it happens slowly their body can adjust.
What type of leucopenia are doctors most worried about and is most common?
Neutropenia (neutrophils are too low)
What are symptoms of leucopenia?
Recurrant bacterial skin infections, mouth ulcers, overwhelming sepsis and more unusual infections.
What are symptoms of thrombocytopenia?
Bruising, gum bleeding, nose bleeds, petechiae (rash), rash as back of mouth (normally due to a brain bleed) and prolonged bleeding from cuts.
What are erythrocytes main function?
carry oxygen around the body
Do RBC’s have osmotic equilibrium and flexable membranes?
yes
What blood cells survive the longest in the blood?
red blood cells (3 months)
How is haemoglobin made up?
Has 4 globin chains (in adults this is HbA alpha 2 and beta 2) (infants this is alpha 2 and gamma 2 chains). These are linked to 4 haem moieties - iron and protoporphyrin which can bind to oxygen
What can cause anaemia?
Blood loss
What types of illnesses can cause anaemia through reducing RBC production?
Iron deficiency (most common) , B12/folate deficiency, malignancy and thalassaemia ()
How does an iron deficiency cause anaemia
Haem needs iron to bind oxygen and when there is less iron in the body there is less haem.
How does B12 and folate deficiency cause Anaemia?
These are needed for DNA synthesis and lack of this means RBC’s cannot be produced
What are haemotinics?
Iron, B12 and folate as these are the most common causes of anaemia
What is thalassaemia?
Inherited defects of haemoglobin synthesis
What diseases cause anaemia through increased RBC production?
Haemolysis (e.g. autoimmune diseases) and sickle cell disease.
What causes iron deficiency?
- Chronic blood loss such as menstruation or gastrointenstinal bleeding (common in older people as it is more common for them to get bowel cancer than younger people)
- Diet (vegetarian, vegan, toddlers)
- Malabsorption (coeliac disease, gastric surgery)
- Increased requirements (pregnancy, growth).
Can you spot iron deficiency anaemia?
Yes - cells will be paler and smaller, there is also pencil cells which is common in iron deficiency anaemia.
What causes Megaloblastic anaemia?
Defective DNA synthesis causing the RBC’s being produced to grow significantly larger and not divide.
What is the most common cause of megaloblastic anaemia?
B12/ folate dificiency which would then need to be tested for and replaced.
Megaloblastic anaemia - Macrocytic anaemia (increased MCV) shows you what on the blood film?
Oval macrocytes, neutropenia with hypersegmented neutrophils, thrombocytopenia (low platelet levels), Reduced reticulocytes (young cells) and large red cells
What causes a folate deficiency?
- Dietary sources usually include green vegtables and therefore inadequate intake (e.g. vegans),
- malabsorption (e.g. coeliac disease),
excess consumption (pregnancy) - drugs (e.g. anticonvulsants).
What causes vitamin B12 deficiency?
- B12 is found in meat, dairy and fish and therefore not eating enough could give you the deficiency (e.g. vegans)
- Autoimmune diseases such as pernicious anaemia (B12 needs factors to be absorbed - these factors come from the pernicous cells in the stomach and pernicious anaemia is when the pernicious cells are reduced).
- Malabsorption (e.g. gastric or ileal surgery - comes from the pernicious cell idea (these are lost in surgery)).
What is Haemolytic anaemia
When red cells are destroyed and can be either inherited or acquired
What are biochemical sign of haemolytic anaemia?
Spherocytes or fragments, anaemia and reticulocytosis, raised bilirubin and LDH.
What can hereditary haemolytic anaemia cause?
Membrane and cytoskeleton defects (spherocytosis, elliptocytosis)
Issues with enzymes (Defective RBC metabolism (G6PD, pyruvate kinase deficiency))
Haemoglobin (Haemoglobinopathies (sickle cells, thalassemia))
What would you see on a blood film of hereditary spherocytosis
More spherical red blood cells, paler red blood cells.
What causes autoimmune haemolysis (AIHA)?
Antibody starts to be produced in the body against the bodies RBC.
What tests would you use and expected results when suspecting AIHA?
Direct coombs/antiglobulin test which would test positive. This tests to see if RBC’s are coated in immunoblobin or complement in vivo after spinning and washing the blood.
Where are Haemoglobinopathies more common in and why?
Africe, asia and the mediterranean as they have a selective advantage over malaria (someone with this cannot get malaria) and this is why it is more passed on through generations.
What is thalassemia?
Reduced rate of synthesis of normal globin chain and haemolysis
What is sickle cell disease?
When abnormal haemoglobin is synthesised which causes haemolysis and vaso-occlusive complications.
What would you see on a blood film showing thalassemia?
Red cells are smaller and paler (similar to iron deficiency but more pronounced and iron will be normal).
What would you see on a blood film for sickle cell disease?
All blood cells are sickle cells.
