Lecture 1 - Hematopoiesis & Hematological Parameters Flashcards
Define Hematopoiesis
Process whereby blood cells are made.
Infants have hematopoietic marrow in all ______, but in adults it’s in the ____________ & ___________.
- all bones
- central skeleton
- proximal ends of long bones
Explain what it means that the bone marrow has an enormous production capacity.
- In the bone marrow, it is estimated that 10 to the power of 10 (1010) erythrocytes & 10 to the power of 8 to 10 to the power of 9 leukocytes are produced per hour in the steady state.
- Furthermore, while cell numbers are maintained within fairly narrow limits, they can be greatly amplified on demand.
Hematopoietic stem cells (HSCs)
- are mostly in a resting or non-dividing state.
- have the capacity to self-renew (& thus maintain their numbers)
Hematopoiesis involves the complex physiological processes of:
- proliferation
- differentiation
- apoptosis
Extra-medullary sites for hematopoiesis
- spleen
- liver
- lymph nodes
- adrenal glands
- kidney
- cartilage
- adipose tissue
- thoracic paravertebral gutters
Define Extra-medullary hematopoiesis
the production of mature erythroid and myeloid progenitor cells outside of the bone marrow
Why does extra-medullary hematopoiesis occur?
- It is a physiological response to chronic anemia. It occurs in hematological diseases such as thalassemia, sickle cell anemia, primary myelofibrosis, infiltrative diseases of the bone marrow such as granulomas or metastatic
cancer etc.
Properties of Hematopoietic Stem Cells (HSC)
- 2 critical ones
- Ability to self-renew
- Property of multi-potency
Some diseases treated by hematopoietic stem cells (HSC)
- Acute & Chronic leukemia
- Lymphoma
- Sickle cell anemia
- Aplastic anemia
- Thallasemia
Assessment of Hematopoiesis
- FBC
- Bone marrow aspiration (allows assessment of the later stages of maturation of hematopoietic cells)
- Trephine biopsy (provides a core of bone & bone marrow to show architecture).
- Reticulocyte count = young red cells (gives an indication of the output of young red cells by the bone marrow).
Define Hematocrit
- the proportion of a sample of blood taken up by red cells.
- The amount of whole blood that is made up of red blood cells.
Define Mean Cell Volume (MCV)
- The average volume of circulating red cells.
- Measurement of RBC size
Define Mean Cell Hemoglobin (MCH)
- the average hemoglobin content of RBCs.
- amount of hemoglobin in a RBC.
What are Peripheral Blood Cells?
Peripheral blood is the blood circulating throughout the body. The cellular components that could be isolated from human peripheral blood include erythrocytes (red blood cells), leukocytes (white blood cells), and thrombocytes (platelets).
Explain structure of Hemoglobin
- Normal adult hemoglobin contains 4 globin (polypeptide) chains = alpha 1 & 2, beta 1 & 2; each with its own heme molecule.
- These globin/polypeptide chains undergo conformational change & move with respect to each other when binding O2 & CO2.
- 2,3-Diphosphoglycerate (2,3-DPG) binds between the beta chains to reduce affinity for O2 & allow O2 release to the tissues.
Pathological variants of Hemoglobin (Hb) can cause…
Tissue hypoxia & tissue excessive oxygenation.
What are Reticulocytes?
- newly formed red cells that have lost a nucleus but retain some RNA.
- they synthesize proteins.
- RNA is lost after about 48 hours and the reticulocytes are then mature red cells.
Normal range for Reticulocytes
1-3% of red cells or 50-150 x 109/L
Importance of Reticulocyte count
- measures new red cell production by the marrow.
- raised = after hemorrhage or hemolysis when extra red cell production is needed.
- low = if the marrow is incapable of normal red cell production.
Define Hematinic & give examples
- substances that are essential to the proper formation of the components of blood.
e.g. serum iron, serum folate, serum vitamin B12, serum ferritin.
What is Erythropoietin?
- hormone that controls the production RBCs.
Where is Erythropoietin produced?
- produced in the peritubular complex of the kidney (90%), liver & other organs.
Function of Erythropoietin
- stimulates mixed lineage & red cell progenitors;
as well as pronormoblasts & early erythroblasts to proliferate, differentiate & synthesize hemoglobin.
Erythropoietin secretion is stimulated by?
reduced O2 supply to the kidney receptor
Principal stimuli to RBC production
- tissue hypoxia
& - reduced hemoglobin concentration (anemia) which acts through the Hypoxia Inducible Pathway (HIF).
What does exogenous erythropoietin bind to?
binds to the erythropoietin receptor on the surface of the red cell & initiates a signal transduction by phosphorylation of the Janus Kinase 2 (JAK2). This in turn induces gene transcription & red cell proliferation.
In Polycythemia rubra vera (PRV), mutations occur in?
mutations in JAK2 which causes pathological increase in red cell production.
________ RBCs are produced every day
200 billion
Mature red cells have no what?
have no:
- nucleus
- ribosomes
- mitochondria
Explain red cell metabolism
