2 - Erythropoiesis Flashcards
Erythropoiesis
Formation and life cycle of RBC
Where does RBC form before birth? (3 Stages)
Mesoblastic stage – 3rd week, nucleated red blood cells form in Yolk sac and mesothelial layers of placenta
Hepatic stage – 6 weeks, Liver & Spleen
Myeloid stage – 3rd monthonwards, bone marrow becomes principal source of RBC
Where does RBC form after birth? (3 stages)
Up to 5 years –Bone marrow in all bones
Age 5 to 20/25 – Marrow of longbones (Femur, tibia)
Age 25+ - Marrow of membranous bones(vertebrae, sternum, ribs, cranial bones)
Yellow Marrow
Fat droplets and cells
Red Marrow
Erythropoiesis
Stages of Erythropoiesis
1 = Haemocytoblast in bone marrow 2 = Common myeloid progenitor (proerythroblast) 3 = Early, late erythroblast and normoblast 4 = Reticulocyte
Erythrocyte size + stain
7.8um diameter, stain with EOSIN, volume of 90cumm
Reticulocyte what are they and percentage
Haveribosomal RNA which shows as dark markings, 1% of red cells are reticulocytes
Proerythroblast what are they
Can differentiate into other blood cells e.g megakaryocyte, myeloblast
Myeloblast what do they develop into
Developinto granulated white cells (granulocytes)
Granulocytes what are they
Part of the innate immune system, neutrophils make up majority
What is the RBC count for male and female
Male 5.2 ± 0.3 x 106 /µL
Female 4.7 ± 0.3 x 106 /µL
Where is EPO produced?
Interstitial cells in kidney proximal tube
What stimulates EPO release?
Hypoxia stimulates EPO secreting cells to release EPO
What does EPO act on ?
Erythropoeitic stem cells
What are the effects of EPO?
Rapid maturation of bone marrow cells, increased reticulocyte, stimulates maturation of erythroblasts in the red bone marrow
Erythrocyte Sedimentation Rate
Non-specific marker of infection
Standard blood test
Raised indicates infection as bacteria release molecules that bind RBC together as they reduce the negative charge on the RBC caused by sialic acid
How does RBC make ATP
Anaerobic glycolysis
What is the RBC lifespan
120 days
How do splenic macrophages detect old RBC
Cell surface antigens are different
Splenic macrophages identify and remove them
Increase in methaemoglobin in the cell
What is the enzyme that converts heme into biliverdin in the macrophage?
Heme oxygenase
What is biliverdin and what colour is it
Opened porphyrin ring minus iron atom
Greenish colour
What is the enzyme that converts Biliverdin to Bilirubin
Biliverdin Reductase
Unconjugated bilirubin
Bilirubin bound to albumin in the splenic macrophages and released into the blood
Conjugated bilirubin
bound to glucuronic acid in the liver by hepatocytes to make it more soluble
Normal level of conjugated bilirubin in the blood
0.1-0.3 mg/dL
Where is bilirubin converted to urobilinogen?
Small intestine
What happens to urobilinogen
90% in faeces
10% in portal vein to liver - to kidney - urine
What can intestinal urobilinogen be oxidised into?
Stercobilin which is excreted in faeces
Why is EPO produced where they are
Kidney has regulated GFR + steady oxygen
the o2 levels are not altered by exercise or BP changes
it is determined by level of haemoglobin in arterial blood
What enzyme breaks down haem
Haemoxygenase enzyme
What colour is stercobilin
Yellow
