Red Blood Cells Flashcards
What is an erythrocyte?
Red Blood Cell
What is a leukocyte?
White blood cell
Where are haemopoietic stem cells produced?
Bone marrow
What is the function of an erythrocyte?
Oxygen transport
What is the function of a neutrophil?
Defence against infection by phagocytosis and killing of microorganisms
What is the function of a monocyte?
Defend against infection by phagocytosis and killing of microbes
Function of eosinophil
Defend against parasitic infection
Function of lymphocyte
Humoral and cellular immunity
Function of platelets
Haemostasis
What are the two main characteristics of HSC’s
Self renew and differentiate into other daughter cells
What two types of cells do MSC’s differentiate into?
Lymphoid stem cells and myeloid stem cells
What do lymphoid stem cells differentiate into?
Lymphocytes and platelets
What do myeloid stem cells differentiate into ?
Erythrocytes, neutrophils, monocytes and eosinophils
Where does haemopoiesis occur in the foetus?
In yolk sac and then liver and then it occurs in the bone marrow
Where does haemopoiesis occur in adults ?
Bone marrow- especially pelvis, femur and sternum
What is a progenitor cell?
A biological cell that like a stem cell has a tendency to differentiate into specific types of cells, but is already more specific than a stem cell and is pushed to differentiate into a ‘ target cell’
What is haemopoiesis regulated by?
Genes, transcription factors, growth factors and micro environment
What diseases may occur is the balance between the proliferation and differentiation of haemopoietic cells are disrupted?
Leukaemia or bone marrow failure
What is one example of a haemopoetic growth factor?
Glycoproteins
What are granulocytes and monocytes stimulated by?
G-CSF, G-MCSF and cytokines ( eg interleukins)
What are megakarycytopoisis and platelet production stimulated by?
Thrombopoietin which is produced in the bone marrow
Describe the development of RBC’s
Myeloid stem cell- proerythroblast-erythroblast(early, intermediate and late) -erythrocytes
What is required for erythropoiesis
Iron, folate and vitamin B12
What regulates erythropoiesis
The growth factor Erythropoietin . It is a glycoprotein that is synthesised in the kidney in response to hypoxia and anaemia. It then stimulates the bone marrow to produce more red blood cells.
What anaemia does B12/folate deficiency cause?
Macrocytic anaemia ( bigger rbcs as they grow and are unavailable to divide)
What causes microcytic anaemia ?
Iron deficiency ( rbcs are smaller)
Describe the molecule of adult haemoglobin
It is a tetramer ( made of 4 subunits - 2 alpha and 2 beta) and each globin chain is bound to a Haem group . Each Haem group contains a ferrous iron ( Fe2+)
What is a porphyrin
A ring which holds a Fe2+ ion in haemoglobin. Each Fe2+ ion can bind to one O2 molecule.
Difference between adult and foetal haemoglobin
HbF is made up of 2 alpha and 2 gamma subunit and HbF has a higher affinity for O2 than HbA so the foetus will get more O2 from the mothers blood.
Where is iron absorbed
Duodenum
Which form of iron is more easily absorbed
Haem iron which is animal derived ( Fe2+) is more easily absorbed. The ferric form required the action of reducing substances ( eg, ascorbic acid and vitamin C).
What do phytates do
Bind to iron and reduce absorption ( present in soya beans)
What does hepcidin do
It blocks the absorption and release of storage iron . When iron storage is high, hepcidin synthesis is increased and this binds and degrades ferroportin and do iron is not released into plasma.
Why are vitamin B12 and Folate important
They are needed for dTTP synthesis which is a precursor for thymidine synthesis. Deficiency of vitamin B12 or folate inhibits DNA synthesis . It also affects all rapidly dividing cells ( eg. Bone marrow , epithelial cells of mouth and gut, gonads- reproductive)
Sources of vitamin B12
Meat liver kidney fish eggs milk and cheese oyster and clams , fortified cereals
Sources of folic acid
Green leafy veg cauliflower Brussels sprouts liver and kidney whole grain cereals yeast fruits
Causes of vitamin B12 deficiency
Inadequate intake ( veganism) , malabsorption ( coeliac disease) , lack of acid in stomach ( achlorhydia)
How is vitamin B12 absorbed
b12 combines with intrinsic factor made in gastric parietal cells and the B12 -IF binds to receptors in ileum
What is RDA of folic acid
100 micro gram . Absorbed in small intestine . Requirements increase during pregnancy and increased cell production ( sickle cell anaemia)
What happens during red cell destruction
The erythrocyte circulates for around 120 days and then it is destroyed by the phagocytic cells of spleen ( macrophages). The iron from Haem returns to bone marrow where it is recycled, and bilirubin is excreted in bile
What does erythrocyte function depend on
Integrity of membrane , Hb structure and function and cellular metabolism
How does hereditary spherocytosis occur ?
Caused by the disruption of the vertical linkages in the membrane . Spherocytes are spherical in shape and have a round regular outline and lack central pallor. Form as a result of loss of cell membrane without the loss of an equivalent amount of cytoplasm so cell rounds up. This means they are less flexible snd so are remove prematurely by spleen ( in quality control process) - haemolysis.
What is hereditary elliptocytosis
Disruption of horizontal linkages in membrane produce elliptocytes ( also do not have an area of central pallor )
What diseases do disruptions in the cell membranes of rbs cause
Disruption in vertical linkages- hereditary spherocytosis
Disruption in horizontal linkages- hereditary elliptocytosis
Effect of carbon dioxide on haemoglobin affinity
Carbon dioxide combines with water in the blood to form carbonic acid. This lowers the pH of blood and causes the the curve to shift to the right so lowers haemoglobins affinity to oxygen. So more O2 is released to respiring tissue - Bohr effect.
What causes left shift on Hb dissociation curve
HbF and CO
What causes right shift of oxygen dissociation curve
High CO2 , high 2-3DPG , HbS
What is 2,3-DPG
2,3-Diphosphoglycerate is an organic phosphate which is present in erythrocytes and modulates oxygen affinity of haemoglobin.
What does 2,3-DPG do?
Allosteric effector and it modulates haemoglobin affinity . It binds to B - haemoglobin chain in central cavity of haemoglobin molecule and has a role in anaemia , hypoxia and high altitude.
What does G6PD do?
It is an enzyme which basically protects rbc from oxidant damage . Oxidants may be in blood stream due to infection or may be exogenous ( drugs/broad beans).
What happens in a G6PD deficiency disorder?
It is an X linked inheritance so affected individuals are usually hemizygous males ( occasionally homozygous females). Causes intermittent, severe intravascular haemolysis - when the unstable rbcs break up in the circulation releasing hb into blood.
How does G6PD deficiency change the appearance of the rbcs
They are called irregular contracted cells and are irregular in outline but are smaller than normal cells and have lost their central pallor. The Hb also is denatures and forms round inclusions called Heinz bodies which can be detected by a specific test.
Advantage of G6PD disorder?
Distribution parallels malaria ; selective advantage, resistance to falciparum malaria
Causes of microcytosis
Defect in Haem synthesis: iron deficiency, anaemia of chronic disease
Defect in globin synthesis ( thalassaemia) : defect in alpha chain synthesis ( alpha thalassaemia), defect in beta chain synthesis ( beta thalassaemia)
Diff types of macrocytes
Round macrocytes, oval macrocytes and polychromatic macrocytes
Causes of macrocytosis
Lock of vitamin B12 or folic acid. Liver disease and ethanol toxicity. Haemolysis and pregnancy
Normal colour proportion of rbcs
Normal rbcs have about a third of the diameter which is pale due to hate disc shape of the red cell so the centre has less haemoglobin and is therefore paler
Hypochromia
The cells have a larger area of central pallor than normal . This results from a lower haemoglobin content and conc. and a flatter cell. Hypochromia and microcytosis often go together.
Polychromatic cells
A blueish tinge to the cytoplasm and indicates that the cell is young. Polychromatic cells are larger than normal and polychromasia is one of the causes of macrocytosis
Retikulocytes
Young cells and can detect by doing a new methylene blue stain , this stains for higher RNA content. May occur as a response to bleeding or haemolysis
Anisocytosis
Red cells show more variation in size than is normal - may be due to 2 diff populations of blood cells . E.g. patients with iron deficiency who is receiving replacement therapy
Poikilocytosis
Red cells show more variation in shape than is normal
Examples of poikilocytes
Target cells, sickle cells, fragments, spherocytes , elliptocytes and irregularly contracted cells
What are target cells
Target cells are red cells with an accumulation of haemoglobin in the centre of the area of central pallor . May occur due to : obstructive jaundice, liver disease , haemoglobinopathies, hyposplenism
What are Schistocytes
Fragment/ small pieces of red cells and indicate that red cell is fragmented.
What is the difference between MCH and MCHC
MCH is the absolute amount of haemoglobin in an individual red cell. MCHC is the conc of haemoglobin in an individual red cell. MCHC is related to the shape of the cell. In microcytic and macrocytic anaemia, MCH tends to parallel the MCV
What does mcv mean
Mean cell volume
MCH
Mean cell haemoglobin
MCHC
Mean cell haemoglobin concentration
what is polycythaemia?
too many rbc’s in circulation. the Hb, RBA and Hct are all increased.
causes of polycythaemia?
excessive transfusion and response to hypoxia. erythropoetin is elevated. Erythropoetin may be inappropriately administered or when a kidney or other tumour innapropriately secretes erythropoietin - kidney is major normal site of erythropoeitin production
Another cause of polycythaemia which is independent of erythorpoeitin
innapropriately increased erythropoiesis - condition is an intrinsic bone marrow disorder called polycythaemia vera. it is a myeloproliferative disorder and can lead to vascular obstruction and venous or arterial thrombosis.
