Red Blood Cells Flashcards
Which part of the body do blood cells originate from?
Bone marrow
What are blood cells derived from?
Pluripotent haematopoietic stem cells (HSCs)
Pluripotent haematopoietic stem cells (HSCs)
Self renew
Differentiate to mature progeny
Sites of haematopoiesis
Yolk sac generation of HSC
Liver HSC maintenance and expansions
Bone marrow mainly pelivis femur and sternum
What regulates haematopoiesis
Genes transcription factors growth factors and micro environment
What occurs if regulation disrupted
Can lead to leukaemia or bone marrow failure
Haematopoietic growth factors:
- Glycoprotein hormones which bind to cell surface receptors
- Regulate proliferation and differentiation of HSCs
- Regulate function of mature blood cells
Erythropoietin
Regulated erythropoiesis
Glycoprotein cytokine that regulates erythropoiesis
Made in the kidney in response to hypoxia
It interacts with erythropoietin receptors on red cell progenitor membranes → stimulates bone marrow to increase RBC production
Erythropoiesis
Development of red blood cells
What 4 things are required for erythropoiesis
Iron
B12
Folate
Erythropoietin
When is erythropoietin (EPO) synthesized
Synthesized in response to hypoxia
Iron
Transports oxygen and absorbed in duodenum
Fe2+ best absorbed Fe3+ requires vit c
Hepcidin
Controls absorption of iron so only 1-2mg absorbed. It binds to ferroportin is the duodenum preventing iron absorption
What does B12 bind to
Combines with intrinsic factor making B12-IF
In small intestine it binds to receptors in ileum
Where is Folic acid absorbed
Absorbed in small intestine
B12 deficiency caused by
Inadequate intake
Malabsorption due to coeliac disease
Lack of stomach acid
Where are erythrocytes destroyed
In spleen
Erythrocyte life span
120 days
Erythrocyte shape
Made of lipid bilayer supported by protein cytoskeleton
Spherocytosis when vertical linkages are disrupted
Elliptocytosis is disruption to horizontal linkages occurring in iron deficiency
What gives rise to a proerythroblast
Common myeloid progenitor-proerythroblast-erythrocyte
What deficiency gives microcytic anaemia
Iron deficiency
What gives macrocytic anaemia
B12 or folate deficiency
Use of drugs interfering with dna synthesis
Liver disease and ethanol toxicity
Haemolytic anaemia
Reduction of B12 and folate
Causes dttp deficiency so thymidine can’t be made so dna can’t replicate affecting cells in bone marrow which can’t divide , epithelial surfaces and in mouth and gut
Anaemia
Is the reduction in the amount of haemoglobin present in a given volume of blood
Haemolysis
Rbc become less flexible so are removed prematurely by spleen
Anemia of chronic disease
Caused by autoimmune disease malignancy inflammatory conditions kidney disease and infections. Iron supplements won’t help patients
Glucose 6 phosphate dehydrogenase deficiency
X linked disorder
Is a haemolytic anemia which results from cells inability to make glutathione.increases susceptibility to oxidative damage and cell death. Heinz bodies are markers for oxidative damage.
Intravascular haemolysus
Causes bite cells
What is the most abundant cytoskeletol protein
Spectrin
Increased hepcidin means
Less iron absorption less iron transport and less iron available to red blood cells
Howell jolly bodies
Erythrocytes which fail to expel a fragment if dna during maturation seen as a blue dot in the cell. Can be indicative of spleen malfunction so related to sickle cell anaemia and megaloblastic anaemia
What is anaemia
Reduction in the amount of haemoglobin in a given volume of blood. Due to rbc failure of production or destruction
Hypochromia
Cells have a larger central pallor so less haemoglobin and flatter cell(usually looks like it has a hole)
Causes of microcytic anaemia
Iron deficiency
Anaemia of chronic disease
Thalassaemia
(Globin synthesis defect)
Defect in B chain or a chain synthesis
Reduced ferritin
Reduces hepcidin production
Increased iron supply
Polychromasia
Blue tinge in cell cytoplasm
Indicates red cell is young
Cells are larger than normal rbc
Target cells
Red cells with accumulation of haemoglobin
Occur due to obstructive jaundiced
Liver disease
Haemoglobinopathies
Hyposplenism
Look like donuts
Sickle cell anaemia
Caused by mutation in b globin gene
Causes sickle shaped rbc
Carriers of one gene have the sickle trait but are asymptomatic
Megaloblast
Abnormal erythroblast which is larger than normal caused by vitamin B12 deficiency or folate and is a cause if macrocytic anaemia
What 3 mechanisms results in anaemia
Reduced production of red cells by bone marrow eg iron deficiency B12 or folate or leukamia
Loss of blood eg gastrointestinal bleeding
Reduced survival of red cells eg sickle cell disease G6PD deficiency and sperocytosis
Why do patients with sickle cell not feel fatigued
As there is decreased affinity of HbS binding to oxygen
What is 2,3 DPG
Modulates oxygen affinity by binding to haemoglobin
Increasing 2,3 DPG means oxygen is released from haemoglobin
- Megakaryocytopoiesis and platelet production growth factor?
Thrombopoietin
Heteroplasmy
In thalasemmia the more chains that are affected the more sever the symptoms out of the 4 Globin chains
Polycythemia
Too many red blood cells
Due to over transfusion,hypoxia,inappropriate erythropoietin use
Leads to thickening of blood
