Red Blood Cells Flashcards
What is haematopoiesis?
Formation and development of blood cells
What is erythropoiesis?
Formation of red blood cells
Where are RBCs produced?
Bone marrow
What are RBC’s derived from?
Pluripotent haematopoietic stem cells (HSCs)
HSCs give rise to lymphoid stem cells and myeloid stem cells
What are 2 characteristics of HSCs?
They self renew- some daughter cells remain as HSCs
They differentiate to mature progeny- other daughter cells follow a different pathway
What are sites of haematopoiesis in a fetus?
YOLK SAC: - 3 weeks -HSCs derived from mesoderm -Primitive RBCs, Platelet precursors and macrophages made here LIVER: - 6-8 weeks -HSC maintenance and expansion BONE MARROW: - approx. 10 weeks -starts developing haematopoietic activity
What are sites of haematopoiesis in an adult?
Mainly in bone marrow
What are sites of haematopoiesis in children?
Occurs in nearly all bones
What is haematopoiesis regulated by?
Genes, transcription factors, growth factors and microenvironment
What does disruption in the regulation of haematopoietic stem cells result in?
Disturbs the balance between proliferation and differentiation and can lead to leukaemia or bone marrow failure
What growth factors are involved in the regulation of haematopoietic activity?
Glycoprotein hormones bind to cell surface receptors and regulate proliferation and differentiation of HSCs and regulate function of RBCs
They’re synthesised in the kidney
Granulocyte and monocyte production requires growth factors G-CSF and G-M CSF
What hormone does erythropoiesis require?
Erythropoietin
It’s mainly synthesised in the kidneys when they detect hypoxia and anemia
90% is made in juxta tubular interstitial cells of kidney
and 10% from liver
What is the role of erythropoietin?
It’s a glycoprotein hormone which stimulates the bone marrow to make more RBCs
How are RBCs made
Common myeloid progenitor can give rise to proerythroblasts
Proerythroblasts gives rise to erythroblasts and erythrocytes
What are nucleated RBCs?
Nucleated RBCs are immature RBCs- they’re released because there’s a high demand for bone marrow to produce RBCs
What are requirements for erythropoiesis?
Iron, Folate, Vitamin B12, Erythropoietin
How long is a RBCs life cycle?
120 days
How are RBCs destroyed?
Macrophages of spleen detect old RBCs and destroy them
RBC destruction releases globin and Haem
What does Haem release?
Haem releases iron and bilirubin
Bilirubin is taken to liver, stored and eventually excreted into gut
What happens to iron once its been released by a RBC?
Iron is recycled to bone marrow
What does DNA synthesis need?
Adenosine, Thymidine, Cytidine and Guanosine- these come from dATP, dTTP, dGTP and dCTP
What do you need to make dTTP?
B12 and folate- deficiency of there means thymidine can’t be made so you cant made DNA so you cant make new cells
What does B12 and folate deficiency affect?
Affects all rapidly dividing cells e.g. epithelial surface of gut and moth, bone marrow and gonads
Where does B12 come from?
Meat, eggs, dairy
Where does folate come from?
Leafy green vegetables
How is B12 absorbed?
STOMACH:
B12 combines with intrinsic factors (IF) made in gastric parietal cells
SMALL INTESTINE:
B12-IF binds to receptors in ileum
What are causes of B12 deficiency?
- Inadequate intake
- Lack of acid in stomach
- Pernicious anaemia: parietal cells of IF destroyed by antibodies
- Malabsorption
Where in the body is iron from diet absorbed?
Duodenum
What type of iron is best absorbed?
Haem iron is ferrous iron (Fe2+) and is from meat
It’s absorbed better than ferric iron (Fe3+)
How is ferric iron absorbed?
Fe3+ needs to be reduced to ferrous iron (Fe2+)
What reduces iron absorption?
Phyates in food
Whats the problem of high iron levels in the body?
Toxic- excess iron can’t be excreted
How much iron does the body absorb a day?
about 1-2mg
What is iron carried by?
Transferrin
What is microcytic?
Red blood cells are smaller than normal or anaemia with small red cells. Tends to be alongside hypochromia
What is normocytic?
Red blood cells of normal size or anaemia with normal sized red blood cells
What is macrocytic?
Red blood cells that are larger than normal or anaemia with large red blood cells.
Macrocytes can be round,oval or polychromatic.
Tends to go alongside polychromasia
What proportion of a normal red blood cell is pale?
1/3- centre has less hb so is paler
What is hypochromia?
Cells have larger area of pallor than normal. Results from lower Hb content and flatter cell
What is polychormasia?
means many colours- increased blue tinge to cytoplasm. Indicates that a cell is young.
Polychromatic cells are larger than normal RBCs
What are causes of microcytosis?
Defect is haem synthesis
Iron deficiency
Anaemia of chronic disease
Defect in globin synthesis (a thalassemia or b thalassaemia)
what are causes of macrocytosis?
lack of vitamin B12 or Folic acid (megaloblastic anaemia)
liver deficiency and ethanol toxicity
Haemolysis (polychromasia)
Pregnancy
How can you detect young red blood cells?
Use new methylene blue stain- this stains their high RNA content
What are reticulocytes?
immature RBCs, larger than mature RBCs
What is reticulocytosis?
refers to presence of increased reticulocytes (due to bleeding or RBC destruction)
What word describes the variation in size of RBCs?
Angiocytosis
What word describes the variation in shape of RBCs?
Polikocytosis
In what conditions can angiocytosis and polikocytosis occur?
Liver disease, Obstructive Jaundice, haemoglobinopathies and hyposplenism
What are sickle cells?
Sickle or crescent shaped cells
What causes sickle cell disease?
Result from the polymerisation of HbS- its deoxygenated form is much less soluble than HbA
HbS occurs when one or more copies of the abnormal B chain are inherited
Caused by mutation in B globin gene- charged glutamine residue in position 6 is replaced by an uncharged valine
What are eliptocytes?
Cells don’t have area of central pallor
Eliptocytes may occur in iron deficiency
What causes hereditary eliptocytosis?
Disruption in horizontal linkages in membrane
What are red cell fragments?
Fragments or chistocytes are small pieces of red cell
Indicate a cell has fragmented- may be due to sheering process caused by a platelet
what are spherocytes?
RBCs that are spherical- lack central pallor
Result from loss of membrane
They’re less flexible and are removed prematurely by spleen
What causes hereditary spherocytosis?
Disruption in vertical linkages in membrane
What is a reference range?
Comes from a defined population- normal range is a more loose concept. It’s a 95% range
Normal range can be affected by : age, gender, ethnicity, altitude etc.
How is a reference range determined?
Sample collected from healthy volunteers with defined characteristic
Analysed using instrument and technique used for patient sample
Data is analysed
What’s an appropriate statistical technique when analysing reference ranges?
Data with normal distribution can be analysed with mean and SD: 95% reference range means +/- 2SD
Data with different distribution can’t be analysed with mean and SD
What can a normal distribution also be called?
Gaussian distribution
What are caveats of reference ranges?
not all reference ranges are abnormal
Not all results within the reference range are normal
What is G6PD?
Glucose-6-phosphate dehydrogenase is an important enzyme in the hexose monophosphate (HMP) shunt
HMP shunt is tightly coupled to glutathione metabolism which protects RBCs from oxidant damage
What caused G6PD deficiency?
X- link inheritance. Gene for G6PD is on X chromosome- affected individuals are normally homozygotic males
What are symptoms of G6PD deficiency?
Intermittent severe intravascular haemolysis (result of infection or exogenous oxidant)
Episodes of intravascular haemolysis is often associated with appearance of irregular cells: irregular in outline, small and have less pallor- sometimes called hemighosts
What causes hemighosts?
Oxidant damage to RBC membrane and Hb
Hb is denatured and forms round clusters called heinz bodies
What regulates iron and how?
Hepcidin
In duodenum, ferroportin on enterocyte transfers iron from cell into bloodstream
If Fe stores are high liver makes hepcidin
Hepcidin degrades ferroportin so any Fe in enterocyte stays bound to ferritin
What inhibits hepcidin?
Erythropoietin inhibits hepcidin (ensures sufficient supply of iron to bone marrow)
