Erythropoiesis Flashcards
What is the mesoblastic stage?
3rd week of foetal development
Erythrocytes develop in the yolk sac and mesothelial placental layers
What is the hepatic stage?
6th week of foetal development
Erythrocytes develop in the liver and spleen
What is the myeloid stage?
3 months onwards during foetal development
Erythrocytes develop in bone marrow
Where are erythrocytes developed in children up to 5?
Bone marrow of all bones
Where are erythrocytes developed in people aged between 5 and 20/25?
Bone marrow of long bones
Where are erythrocytes developed in people aged above 25?
Bone marrow of membranous bones
What is myeloid tissue
Bone marrow
Unit of measurment for blood count?
Cubic l
What is the normal erythrocyte count for men?
5.2+/-0.3*10^6
What is the normal erythrocyte count of women?
4.7+/-0.3*10^6
Where is erythropoietin produced and why
Fibroblast interstitial cells around proximal convuluted tubule of kidney
Oxygen levels here only determined by carrying ability of blood. EPO cells sensitive to hypoxia, so if hypoxia occurs must be to do with oxygen carriage
Effects of EPO (2)
- Rapid maturation of committed bone marrow cells
- In 1-2 days increases number of circulating reticulocytes
Effect of testosterone on EPO
Enhanced EPO production (hence why boys have higher RBC count)
What is a rouleaux
Stack/ clump of RBCs
What causes increased number of rouleaux
Inflammatory reactions or abnormal protein levels reduces negative charge on erythrocytes so they clump together
What is effect of rouleaux in blood test
Settle more quickly due to increased density. Non specific marker of infection
What do red blood cells require ATP for?
Protein pumps and GLUT1 transporters
How do red blood cells gain ATP?
Anaerobic glycolysis
How do red blood cells gain NAPDH?
Pentose phosphate pathway
What is glutathione
Reducing agent in blood that scavenges reactive oxygen and is oxidised in process
What do reactive oxygen species do?
Form in cells and convert ferrous iron in haemoglobin to ferric iron, giving methaemoglobin.
Action of glutathione reductase?
Regenerates glutathione by using NADPH as electron donor.
What is the only non-mitochondrial source of NADPH?
Hexose monophosphate shunt
How do they splenic macrophages detect old erythrocytes?
- Changes in cell surface antigens
- Changes in deformability
What initially happens to trapped RBCs
Engulfed by splenic macrophages and broken open by osmotic lysis
Product of osmotic lysis of RBCs?
Globin proteins and haem group
What happens to globin proteins after osmotic lysis?
Broken to amino acids
Action of haemoxygenase enzyme on haem group?
Breaks into biliveroin
Action of biliverdin reductase in biliveroin
Breaks into bilirubin which then binds to albumin and is transported out spleen into blood
What form is bilirubin when in splenic blood
Unconjugated
Where and how does bilirubin become conjugated
Liver
Bound to gluronic acid by hepatocytes
Effect of conjugating bilirubin
Becomes more water soluble
Where does conjugated bilirubin get transported to
Small intestine
What happens to 90% of conjugated bilirubin
Converted to urobilogen and excreted as faeces
What happens to 10% of conjugated bilirubin
COnverted to urobilogen and goes to liver via portal vein. Then goes to kidney and excreted as urine
What is urobilogen further oxidised to
Stercobilin
What 2 cells does the haematopoetic stem cells differentiate into
Common lymphoid progenitors
Common myeloid progenitor/ proerythroblast
Describe changes undergone by proerythroblast to form erythrocyte
- Differentiates into erythroblast
- Nucleus shrinks
- Cytoplasm fills with haemoglobin
- Now reticulocyte
- Reticulocyte expels nucleus
Name 3 cells (not including erythrocyte) that proerythroblast can differentiate into
- Megakaryocyte
- Mast cell
- Myeloblast
What do myeloblasts differentiate into
Granulated white cells
What do common lymphoid progeniors differentiate into
Lymphocytes
What is the diameter of an erythrocyte
7.8
What do erythrocytes stain with
Eosin
What is the volume of erythrocyte
90 cu mm
Why do reticulocytes show dark marks when stained
Ribosomal RNA stains darker
What % of blood cells are reticulocytes
Approx 1%
Name the granulocytes
Basophil Neutrophil Monocyte Eosinophil Macrophage
What is a macrophage produced from
Monocyte
A rise in what is thought to signal for RBC to be removed from circulation
Increase in methamoglobin
What is the normal level of conjugated bilirubin in the blood
0.1-0,3mg/dl
What gives urine its yellow colour
Urobilirubin
