Haematopoiesis Flashcards
What are the 2 components that make up blood?
Cells
Plasma
What does plasma contain?
Water
Small organic compounds (e.g. glucose) + electrolytes
Proteins: albumin, globulins (α, β, γ) + fibrinogen
What is the main function of proteins in the plasma?
Maintain oncotic pressure
Carriers for molecules that aren’t soluble in the blood
List the cells of the blood.
Monocyte/macrophages
Lymphocytes (T + B)
Granulocytes:
Neutrophils
Eosinophils
Basophils
Red cells (small cells):
Erythrocytes
Platelets
How long do the cells of the blood live?
Platelets: 10 days lifespan
Erythrocytes: most common in blood with turnover of 4 months (so need to be constantly produced)
WBCs: hours-days lifespan (neutrophils most prevalent)
EXCEPT
Lymphocytes: long-lived (days-years) due to memory cells
Define haematopoiesis.
Production of all types of mature blood cells -> RBCs (erythropoiesis), WBCs (myelopoiesis + lymphopoiesis) + platelets (thrombopoiesis)
HSCs in bone marrow give rise to all cell lineages through proliferation (mitosis), differentiation (specialization) + maturation
Dependent on glycoprotein growth factors produced by bone stromal cells (exceptions are erythropoietin (kidneys) + thrombopoietin (liver))
Describe stem cell potency in order from most potent to least potent (early in development to later in development).
Totipotent: differentiate into any cell type including embryonic + extraembryonic (e.g. fertilised egg)
Pluripotent: differentiate into any cell type of embryo (not extra-embryonic)
Multipotent: differentiate into several related cell types
Oligopotent: differentiate into small no. of closely related cell types
Unipotent: produce more cells of identical cell type
What are the 2 lineages of multipotential haematopoietic stem cells (hemocytoblasts)? What do they differentiate into?
Common myeloid progenitor -> megakaryocyte (-> thrombocytes) + RBCs + mast cells + myeloblasts (-> basophil, neutrophil, eosinophil + monocyte/macrophages)
Common lymphoid progenitor -> NK cells + small lymphocyte (-> T + B lymphocytes -> plasma cells)
Where does haematopoiesis occur?
Bone marrow mainly
What does erythropoiesis involve?
Proerythroblast -> erythroblast (basophilic then polychromatic then orthochromatic) -> reticulocyte -> erythrocyte
Erythrocyte maturation includes:
- Decreased cell size
- Hb production
- Loss of organelles e.g. nucleus
- Biconcave disc shape forming
Controlled by EPO + requires iron, folic acid + vit B12
What the characteristics of erythrocytes? What is the purpose of these?
Biconcave disc shape:
- Maximise SA
- Minimise distance from surface
- Increases flexibility
Structural proteins needed to maintain shape
Simplified internal structure with simplified metabolism as they lack organelles so they can be packed full of Hb - only really carry O2 + CO2
What are the 2 requirements of erythropoiesis?
DNA synthesis - requires Folic acid & cobalamin (vit B9 & B12) + IF
Hb synthesis: α2 β2 globins (protein/polypeptide chains) + haem (contains Fe) - requires vit B6 + fE2+
Why is the purpose of folic acid and cobalamin in erythropoiesis? What can deficiency of these cause?
Folic acid/folate/vit B9: required for DNA synthesis + cellular proliferation
Cobalamin/vit B12: recycles folic acid
Lack of either leads to megaloblastic anaemia although if folic acid in excess, vit B12 deficiency effects can be ameliorated
How are folic acid (B9) and cobalamin (B12) absorbed and stored? What can cause deficiency?
B9 absorbed in duodenum + jejunum, normal stores last 3-7 months + deficiency arises from inadequate intake, malabsorption, increased demand + drugs (e.g. alcohol)
B12 absorbed in terminal ileum, normal stores last 3-4 years + deficiency usually due to malabsorption
What is intrinsic factor (IF) and what does it do? What can deficiency cause?
Glycoprotein produced by parietal cells of stomach, it binds to vit B12 + is essential for its absorption in ileum
Lack of IF (most often due to autoimmune response to parietal cells) leads to pernicious anaemia (megaloblastic anaemia)
What is essential for the synthesis of haem groups of haemoglobin?
Occurs by a metabolic pathway with steps in mitochondria + cytoplasm
Vit B6 essential co-enzyme
What inherited disorders can occur of haemoglobin?
Several disorders of the globin chains e.g. α or β thalassaemia + sickle cell anaemia
Disorders of haem synthesis called porphyrias
What is sickle cell anaemia?
A inherited disorder of Hb’s globin chains that causes a single base pair change in DNA in gene for HbA (point mutation where A + T have switched) forming HbS
Molecular properties of HbS are different; cause aggregation + a very different structure of RBC
What are the 2 types of dietary iron?
- Heme iron (from meat)
2. Non-heme iron (from green veg)
How is iron absorbed?
Some is taken up by cells + forms a complex with ferritin (rest lost in faeces)
Most is lost back into intestinal lumen (sloughed off) + lost in faeces but some is transported across basolateral membrane by ferroportin
Transported in blood by transferrin
How is iron stored after absorption into blood from the intestinal lumen?
Most transported to bone marrow + used to make haem for Hb
Remainder stored in liver +spleen or used by other tissue cells in enzymatic processes
How is iron absorption regulated?
Regulated according to need by hormone hepcidin which is released by the liver
Hepcidin inhibits Fe absorption when Fe levels too high by decreasing ferroportin activity on basolateral membrane of intestinal epithelial cells
What is iron deficiency? What can cause it?
Deficiency of Fe leading to decreased amounts of Hb which in turn decrease RBC production
Causes: blood loss, diet low in Fe or poor Fe absorption
What is pernicious anaemia (vit B12 deficiency)?
RBCs do not develop as normal due to a lack of vit B12 + folic acid which causes decreased RBC production
Causes: Lack of IF, diet low in B vits or decreased vit B absorption
What is aplastic anaemia? What can cause it?
Bone marrow unable to produce enough blood cells (life threatening condition)
Causes: cancer therapy, exposure to toxic substances, autoimmune disorders + viral infections
What is haemolytic anaemia? What can cause it?
RBCs destroyed faster than bone marrow can replace them
Causes: inherited causes e.g. sickle cell + thalassaemia
What is anaemia of chronic diseases? What diseases can cause it?
Various illnesses over a long time can reduce RBC production e.g. rheumatoid arthritis, kidney disease, diabetes, TB or HIV
What can different types of anaemia be caused by?
Microcytic/hypochromic: Fe deficiency, thalassaemia + anaemia of chronic diseases
Normocytic/normochromic: after acute blood loss, haemolytic anaemias, anaemia of chronic diseases + bone marrow failure
Macrocytic: Vit B9/B12 deficiency, aplastic anaemia, liver disease + excessive alcohol intake
Define the different types of anaemia.
Macrocytic: anaemia involves large RBCs but in low no. with low Hb
Microcytic: anaemia involves small RBCs + low Hb
Normocytic: anaemia involves RBC of normal size but inadequate no.s
How are WBCs stained?
Haematoxylin & Eosin (H&E)
What is leucocytosis? What are the various forms of this?
High white cell count
Neutrophilia: acute bacterial infections, inflammation, tissue necrosis, drugs, neoplasm etc.
Eosinophilia: allergic disorders e.g. asthma, hay fever etc.
Lymphocytosis: viral infections etc.
What is leukopenia? What are the different diseases that cause this?
Low white cell count
Aplastic anaemia Hypersplenism Sepsis Infection Drugs
What is thrombopoiesis?
Megakaryoblast -> promegakaryocyte -> megakaryocyte -> thrombocytes/platelets
Megakaryocytes in bone marrow adjacent to blood sinusoids + segments protrude into cytoplasm of sinusoids -> blood flow splits off cytoplasmic fragments which become platelets
Platelets circulate in blood for 7-10 days - 40% located in spleen
What is thrombocytosis? What are the 2 forms of it?
High platelet count
Primary: myeloproliferative disorders
Secondary: infection, neoplasms, drugs etc.
Thrombocytopenia? What are the 2 ways in which it can come about?
Low platelet count
Decreased production: genetic disorders, folate/cobalamin deficiency
Increased destruction: hypersplenism, immune destruction, infection + drugs
How is erythropoietin (EPO) produced?
Released by fibroblasts in kidney
What is the stimulus for EPO release?
Cellular hypoxia
What is the mechanism of EPO release?
Binds to receptor on basophilic erythroblasts
-> promotes cell survival
= erythropoiesis in bone marrow
Where is thrombopoietin produced?
Liver + elsewhere
What does thrombopoietin do?
Primarily stimulates differentiation of megakaryocytes + thrombocytes/platelets
Negative feedback loop where thrombocytes then reduce thrombopoietin levels
