Lecture 1 - Hematopoiesis & Hematological Parameters

Question 1

Define Hematopoiesis

Answer 1

Process whereby blood cells are made.

Question 2

Infants have hematopoietic marrow in all ______, but in adults it’s in the ____________ & ___________.

Answer 2

• all bones
• central skeleton
• proximal ends of long bones

Question 3

Explain what it means that the bone marrow has an enormous production capacity.

Answer 3

• 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.

Question 4

Hematopoietic stem cells (HSCs)

Answer 4

• are mostly in a resting or non-dividing state.
• have the capacity to self-renew (& thus maintain their numbers)

Question 5

Hematopoiesis involves the complex physiological processes of:

Answer 5

• proliferation
• differentiation
• apoptosis

Question 6

Extra-medullary sites for hematopoiesis

Answer 6

• spleen
• liver
• lymph nodes
• adrenal glands
• kidney
• cartilage
• adipose tissue
• thoracic paravertebral gutters

Question 7

Define Extra-medullary hematopoiesis

Answer 7

the production of mature erythroid and myeloid progenitor cells outside of the bone marrow

Question 8

Why does extra-medullary hematopoiesis occur?

Answer 8

• 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.

Question 9

Properties of Hematopoietic Stem Cells (HSC)
- 2 critical ones

Answer 9

1. Ability to self-renew
2. Property of multi-potency

Question 10

Some diseases treated by hematopoietic stem cells (HSC)

Answer 10

• Acute & Chronic leukemia
• Lymphoma
• Sickle cell anemia
• Aplastic anemia
• Thallasemia

Question 11

Assessment of Hematopoiesis

Answer 11

• 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).

Question 12

Define Hematocrit

Answer 12

• 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.

Question 13

Define Mean Cell Volume (MCV)

Answer 13

• The average volume of circulating red cells.
• Measurement of RBC size

Question 14

Define Mean Cell Hemoglobin (MCH)

Answer 14

• the average hemoglobin content of RBCs.
• amount of hemoglobin in a RBC.

Question 15

What are Peripheral Blood Cells?

Answer 15

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).

Question 16

Explain structure of Hemoglobin

Answer 16

• 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.

Question 17

Pathological variants of Hemoglobin (Hb) can cause…

Answer 17

Tissue hypoxia & tissue excessive oxygenation.

Question 18

What are Reticulocytes?

Answer 18

• 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.

Question 19

Normal range for Reticulocytes

Answer 19

1-3% of red cells or 50-150 x 109/L

Question 20

Importance of Reticulocyte count

Answer 20

• 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.

Question 21

Define Hematinic & give examples

Answer 21

• substances that are essential to the proper formation of the components of blood.
  e.g. serum iron, serum folate, serum vitamin B12, serum ferritin.

Question 22

What is Erythropoietin?

Answer 22

• hormone that controls the production RBCs.

Question 23

Where is Erythropoietin produced?

Answer 23

• produced in the peritubular complex of the kidney (90%), liver & other organs.

Question 24

Function of Erythropoietin

Answer 24

• stimulates mixed lineage & red cell progenitors;
  as well as pronormoblasts & early erythroblasts to proliferate, differentiate & synthesize hemoglobin.

Question 25

Erythropoietin secretion is stimulated by?

Answer 25

reduced O2 supply to the kidney receptor

Question 26

Principal stimuli to RBC production

Answer 26

• tissue hypoxia
  &
• reduced hemoglobin concentration (anemia) which acts through the Hypoxia Inducible Pathway (HIF).

Question 27

What does exogenous erythropoietin bind to?

Answer 27

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.

Question 28

In Polycythemia rubra vera (PRV), mutations occur in?

Answer 28

mutations in JAK2 which causes pathological increase in red cell production.

Question 29

________ RBCs are produced every day

Answer 29

200 billion

Question 30

Mature red cells have no what?

Answer 30

have no:
- nucleus
- ribosomes
- mitochondria

Question 31

Explain red cell metabolism