Red cells Flashcards
What is haemopoiesis?
Production of erythrocytes, platelets, megakaryocytic and leukocytes
What substance influences the production of erythrocytes?
Erythropoietin
What are granulocytes?
Basophils, neutrophils, eoisinophils
What factors stimulate granulocyte formation?
Granulocyte colony stimulating factors (G-CSF);
GM-CSF (Granulocyte-macrophage colony stimulating factor)
What factor stimulates platelet formation?
Thrombopoietin
What cells are multipotent?
Myeloid progenitor cells
Lymphoid progenitor cells
What is the function of erythrocytes?
Oxygen transport
What is the function of neutrophils?
Inflammation, phagocytosis of pathogens
What is the function of eosinophils?
Defence against parasitic infection?
What is the function of platelet?
Haemostasis
What is WBC?
White blood count, number of white blood cells in a given volume
What is RBC?
Number of red blood cells in a given volume
What is Hb?
Haemoglobin concentration
What is HCT?
Haematocrit. Proportion of blood made up by cells.
What is MCV?
Mean cell volume, the average size of red cells
What is MCH?
Mean cell haemoglobin, average amount of haemoglobin in a red cell
What is MCHC?
Mean cell haemoglobin concentration, the average concentration of haemoglobin in red cell
What is platelet count?
The number of platelets in a given volume of blood
What do myeloid progenitor cells give rise to during erythropoiesis?
Proerythroblasts –> erythroblasts –> eryhthrocytes
In response to cellular hypoxia , which hormone is released to stimulate erythropoiesis?
Erythropoietin
Where is erythropoietin synthesised and released from?
Kidney
What other hormone stimulates release of erythropoietin?
Testosterone
Which cells secrete erythropoietin?
Juxtatubular cell association with the proximal convoluted tubule
Which factors stimulates the synthesis of erythropoietin?
Hypoxia-inducible factors
Which receptors does erythropoeitin bind onto?
Epo receptors
What proteins carry oxygen in RBCs?
Haemoglobin
How is the haem group arranged?
Haem group is bound to ferrous group held in porphyrin ring
What are the adaptations of RBCs?
Thin cell membranes reduces diffusion pathway for oxygen molecules
No nucleus: Maximum storage capacity of Hb
Biconcave shape: Increases
SA:V ratio
What is the structure of haemoglobin?
Conjugated globular protein with quaternary structure of 2 alpha and 2 beta polypeptide chains.
Each chain is arranged around a haem group.
primary structure: Pseudo-repeating sequence of amino a
Why are haemoglobin molecules soluble?
Hydrophillic and hydrophobic interactions , polarised amino acid variable groups exposed externally, potential to form hydrogen bonds with water,
Why is Hb susceptible to denaturation?
No covalent or disulphide bonding between chains, therefore weakly linked.
How does haemoglobin bind to oxygen?
Iron enables haemoglobin to bind and release oxygen molecules, changing shape to the polypeptide chains (conformational change).
What form of iron is absorbed in duodenum?
Ferrous (Fe2+)
What form is non-haem iron presented in?
Ferric (Fe3+)
What reducing substances convert ferric iron to ferrous?
Vitamin c, ascorbic acid
Which molecules reduce absorption of iron?
Phytates
Why is excess iron toxic?
Free radicals , no physiological excretion of iron
What molecules does hepcidin bind onto?
Ferroportin (Iron export protein)
What is ferroportin?
Iron export protein
What happens to ferroportin upon hepicidin binding?
Internalisation of ferroportin, ferrous iron is thereby sequestered within the enterocyte prevents efflux of iron
Where does hepicidin act?
Gut, enterocytes
How is hepcidin synthesis suppressed?
Erythropoietic activity, ensuring iron supply by increasing ferroportin in the duodenum enterocyte (maximising iron absorption)
What happens to hepcidin synthesis during elevated iron levels?
Increases hepcidin synthesis, therefore iron sequestration increases, ferroportin degrades
What is the role of macrophages in iron regulation?
Macrophages release iron that recycle in the spleen; dietary absorption in the duodenum, releases iron from storage in hepatocytes
How is hepcidin influenced during inflammation?
Hepcidin production is stimulated, and iron entry into plasma is inhibited causes hypoferrenia and anaemia
How is iron reduced to Fe2+?
Duodenal cytochrome b binds to divalent metal transporter on apical membrane.
how is iron stored?
Iron is stored as ferritin or oxidised
How is iron delivered to the bone marrow?
Plasma iron bound to transferrin
What is the function of b12 and folate?
Necessary for the synthesis of thymidine, thus deficiency will result in the inhibition of DNA synthesis
Why do erythroblasts require B12 & folate?
Required for proliferation during differentiation
What happens during b12 and folate deficiency?
Inhibits purine and thymidylate syntheses, impairs dan synthesis and causes erythroblast apoptosis
What condition occurs during b12 deficiency?
Megaloblastic erythropoiesis, macrocytosis
How is B12 absorbed?
Hydrochloric stomach acid releases B12
B12 combines with haptocorrin, cleaved by and bound to instrinsic factor
B12-IF Complex traverses into the small intestine, binds to ileum receptors
Taken up by enterocyte and bound to trans cobalamin-II
What molecule cleaves haptocorrin?
Intrinsic factor
What cells secrete Intrinsic factor?
Gastric parietal cells
How is b12-IF complex taken up?
By enterocyte
Where is folate absorbed?
Duodenum & Jejunum
What are the causes for vitamin B12 deficiency?
Inadequate intake of sources containing B12 (Veganism)
Lack of stomach acid (Achlorhydria)
Inadequate secretion of intrinsic factor
Malabsorption
How are erythrocytes destroyed?
Phagocytic cells of the spleen; phagocytic vacuole envelops ingested RBC, lysosome hydrolytic ally digests cell into haem and globin components
What are phagocytic cells of the spleen named as?
Splenic reticuloendothelial macrophages
What is the fate of globin?
Hydrolysed into amino acids, and returned to bone marrow for erythropoiesis
What is transferrin?
Iron binding glycoproteins and is transported to the bone marrow to be incorporated into the synthesis of erythrocytes
What is the fate of the non-iron portion of haem?
Biliverdin converted into bilirubin, binds to albumin and travers to liver to produce bile
What is microcytic anaemia?
RBC are comparatively smaller than the standard, anaemia with the small red cells (Microcytosis)
What is normocytic anaemia?
RBC normal in size, anaemia
What is macrocytosis?
Anaemia with cells larger than standard
What is hypochromia?
Cells have larger area of central pallor than normal, due to lower haemoglobin content and concentration; flatter cell
What is polychromatic?
Blue tinge associated to the cytosol of an erythrocyte, indicates young cell, polychromatic cells are larger than; cause of macrocytosis
What is reticulocytosis?
New methylene blue can be applied to reticulocytes, associated with high RNA content
What is anisocytosis?
Illustrates variation in size than the standard
What is poikilocytosis?
variation in shape
What are the different shapes in RBCs?
Spherocytes, irregularity contracted cells, sickle cells, target cells, ellioptocytes and fragments
What are target cells?
Accumulation of haemoglobin in the centre of the area of central pallor
What codon mutation is concerned with sickle cell?
Codon no/6, charged glutamic acid into uncharged valine
