2.1 Red Blood Cells Flashcards
Where do all blood cells originate
Bone marrow
What are blood cells derived from
Pluripotent haemopoietic stem cells
What do HSC’s give rise to
Common myeloid and lymphoid progenitors (stem cells)
Haemopoiesis
Formation and development of blood cells
Erythrocyte function
Oxygen transport
Erythrocyte life span
120 days
Platelet function
Haemostasis
Platelet life span
10 days
Monocyte function
Defence against infection by phagocytosis and killing of microorganisms
Monocyte life span
Several days
Neutrophil function
Defence against infection by phagocytosis and killing of microorganisms
Neutrophil life span
7-10 hours
Eosinophil function
Defence against parasitic infection
Eosinophil life span
Little less than 7 hours
Lymphocyte function
Humoral and cellular immunity
Lymphocyte life span
Very variable
HSC characteristics
- Self renew
- Differentiate to mature progeny
What do common myeloid progenitors give rise to
Megarakaryocyte (-> platelet)
Erythrocyte
Mast cell
Myeloblast (-> granulocytes and monocytes)
Granulocytes
Basophil
Neutrophil
Eosinophil
What do common lymphoid progenitors give rise to
NK cells
Small lymphocyte (-> T and B lymphocytes,, b-> plasma cell)
Sites of haemopoiesis
- Yolk sac (3 wks gestation) : generation of HSC
- Liver (6-8wks gestation) : maintenance and expansion of HSC
- Bone marrow (10 wks gestation)
Bone marrow as a site of haemopoiesis
Starts developing haemopoietic activity around 10 wks gestation
Occurs in all bones in children
In adults mainly pelvis, vertebrae and sternum
HSC distribution
Ordered fashion within bone marrow amongst mesenchymal cells, endothelial cells and the vasculature which HSCs interact with
What is haemopoiesis regulated by
Number of genes, transcription factors, growth factors and the micro environment
Disruption to balance of haemopoiesis
Disturb proliferation vs differentiation leading to leukaemia or bone marrow failure
What are haemopoietic growth factors
Glycoprotein hormones which bind to cell surface receptors and regulate proliferation and differentiation of HSC and function of mature blood cells
Examples of haemopoietic growth factors
Erythropoietin (EPO) - erythropoiesis
Thrombopoietin (TPO) - megakaryocytopoiesis and platelet production
G-CSF, G-M CSF and cytokines - granulocyte and monocyte production
Erythropoiesis
Development of red blood cells
As differentiation progresses
Self renewal and lineage plasticity decreass
Lineage of RBC changes
Lose nucleus
Change from polychromatic
What is required for erythropoiesis
Iron
B12
Folic acid
Erythropoietin
Microcytic anaemia
Small RBC
due to iron deficiency or low availability
Causes of iron deficiencies
Increased blood loss
Reduced intake
Increased requirement (pregnancy)
Causes of decreased iron availability
Anaemia of chronic disease / inflammation
Macrocytic anaemia
Large RBC
B12/ folate deficiency (megaloblastic anaemia)
EPO synthesised in response to
Hypoxia
Demand supply feedback loop of EPO
Hypoxia -> liver inc EPO synthesis -> inc bone marrow activity <- inc red blood cell production
Iron functions
Oxygen transport in haemoglobin
Mitochondrial proteins ( ytochromes abc)
Signs of low iron
Hyopchromic (pale), microcytic RBC
Gloss it is (inflamed tongue)
Spoon shaped nails
Pale conjunctiva
Where is iron absorbed
Duodenum
Best absorbed iron
Haem iron - ferrous (2)
Animal derived
Non haem iron
Ferric (3)
Requires action of a reducing substance for absorption
Sources of it reduce absorption such as soya beans which contain phytates
Excess iron
Potentially toxic to organs especially the heart and liver
How much iron per day is absorbed form diet
1-2 mg
How is iron transferred
As transferrin in plasma (3mg)
How much iron is in bone marrow
300mg
How much iron in RBC
2500mg
How much iron in reticuloendothelial system
500mg
Iron loss from system
1-2mg a day
Via muscles and enzymes (myoglobin and enzymes)
How much iron in myoglobin and enzymes
300 and 150mg
How much iron in liver
250mg stored as ferritin
How much iron is absorbed in pregnancy
6mg
How is iron absorption regulated
Hepcidin
What is hepcidin secreted by
Liver (in response to high storage iron)
How does Hepcidin work
Blocks absorption of iron from the gut and release of storage iron
Anaemia of chronic disease/ inflammation
Decrease in EPO production causing a decrease in iron production and availability
Pro inflammatory cytokines decrease EPO and inc Hepcidin
What is b12 required for
DNA synthesis
Integrity of nervous system
What is folic acid required for
DNA synthesis
Homocysteine metabolism
DNA synthesis with b12 and folate deficiency
Needed for dttp synthesis for thymidine
Deficiency affect all rapidly dividing cells inc bone marrow. -cells can grow but are unable to divide giving megaloblastic anaemia (macrocytic)
Absorption of b12
Stomach (cleaved with hcl then) combined with intrinsic factor made by parietal cells
Small intestine it binds to receptors in the ileum
Causes of b12 deficiency
Inadequate intake
Inadequate secretion of IF (pernicious anaemia)
Malabsorption (coeliac disease, surgery)
Achlorhydria - lack of acid in stomach
Red cell destruction
Heme excreted as bilirubin in bile, iron from haem transferred as transferrin in plasma and returns to bone marrow where it is recycled
Happens in spleen by macrophages
Haemolytic anaemias
Can be jaundiced due to inc bilirubin levels when actively haemolysing
What does erythrocyte function depend on
Integrity of membrane
Haemoglobin structure and function
Cellular metabolism
Defect in any of these leads to shortened survival (haemolysis)
Central pallor size
No greater than 1/3 its diameter otherwise hypochromic
What’s RBC membrane made up of
Lipid bilayer supported by a protein skeleton
Contains transmembranous proteins
Disruption to vertical linkages in RBC membrane
Causes hereditary spherocytosis
(Autosomal dominant)
Spherocytes
Spherical shape
Lack central pallor
Loss of membrane without equivalent cytoplasm loss
Less flexible and are removed prematurely - haemolytic anaemia
Disruption of horizontal linkages in RBC membrane
Produces hereditary elliptocytosis
Red cell metabolism includes
Generation of atp
Maintenance Hb function, membrane integrity, RBC volume
PPP
Glucose 6 phosphate completely oxidised to CO2
Producing NADPH
NADPH
Provides reducing power for maintaining reduced glutathione- viral antioxidant in RBC
G6PD
Glucose 6 phosphate dehydrogenase maintains reducing power of NADPH
Deficiency causes vulnerability of RBC to oxidant damage
G6PD Deficiency
Manifests in males (X linked inheritance)
Causes intravascular haemolysis (see bite cells)
Bite cells
Irregular outline
Smaller and have lost central pallor
Result from oxidant damage to cell membrane and Hb
Hb is denatured and forms round inclusions called Heinz bodies (on 1 Side of cell) can be detected by specific tests
Polycythaemia
Too many red cells in the circulation
Hb, RBC and hct all increased
Pseudo polycythaemia
Reduced plasma volume due to dehydration etc.
True polycythaemia
Inc in total volume of red cells in circulation
Blood doping, EPO increase
Polycythaemia Vera
Intrinsic bone marrow disorder where an increase in erythropoiesis is independent of EPO
Myeloproliferatuve disorder
Can lead to hyperviscocity (thick blood) which can cause thrombosis
Blood can be removed to reduce viscosity and drugs to reduce by production
