Hematopoiesis Overview and Stages

The process of blood cell formation.
Blood cells are derived from hematopoietic stem cells (HSCs).
HSCs differentiate and proliferate into various blood cell lineages, including myeloid and lymphoid progenitors.
Myeloid progenitors give rise to red blood cells (erythrocytes), platelets, and white blood cells (granulocytes, monocytes).
Lymphoid progenitors give rise to lymphocytes.

Mesoblastic stage: Starts in the blood islands of the yolk sac during embryonic development.
Hepatic stage: Occurs primarily in the liver and spleen, starting at 6 weeks of gestation.
Myeloid stage: Begins around 5 months of gestation, with bone marrow becoming the primary site for hematopoiesis.
Lymphoid stage: Develops in lymph nodes, tonsils, spleen, and thymus.

Glycoproteins:
- Promote the differentiation and proliferation of hematopoietic progenitors.
- Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF): Stimulates myeloid progenitor growth and development in the bone marrow.
- Granulocyte Colony Stimulating Factor (G-CSF): Induces myeloblasts to differentiate into neutrophils.
Hormones:
- Thrombopoietin: A glycoprotein produced by the liver that stimulates the production of platelets.
- Erythropoietin: A glycoprotein produced by the kidney that stimulates the production of red blood cells.

Represent 45% of total blood volume.
Characteristics:
- Anucleate (lack a nucleus).
- Filled with hemoglobin (Hb): A respiratory protein, containing about 30 picograms (pg) in each red blood cell.
- Biconcave discs shaped by the Sceptrin protein.
- Highly flexible due to a high phospholipid membrane.
Lifespan: Approximately 120 days.
Count: 4-6 million/mm³
Factors affecting red blood cell count:
- Diet: Protein, iron (Fe+), and trace minerals.
- Temperature and altitude: Affect oxygen solubility.
- Sex: Males have higher counts than females.
- Age: Newborns have higher counts than older individuals.

The process of red blood cell production.
Stimulated by erythropoietin (EPO) secreted from the kidneys.
EPO production is triggered by tissue hypoxia (low oxygen levels).
Factors that can cause tissue hypoxia: Anemia, high altitudes, cardiac failure, respiratory problems, hemorrhage, athletes.
Other factors influencing erythropoiesis:
- Healthy bone marrow.
- Healthy kidney and liver function.
- Hormones like EPO and non-specific ones like thyroid hormone and androgens.
- Dietary factors: Proteins, fats, and minerals.

Respiratory red pigment found in red blood cells.
Makes up about 34% of red blood cell volume.
A tetrameric protein consisting of four polypeptide chains:
- Adult hemoglobin: Two alpha-globin chains and two beta-globin chains.
- Fetal hemoglobin: Two alpha-globin chains and two gamma-globin chains.
Each polypeptide chain is associated with a heme group.
States:
- T-state (tense): Deoxyhemoglobin, lower oxygen affinity.
- R-state (relaxed): Oxyhemoglobin, higher oxygen affinity.
Functions:
- Carries oxygen and carbon dioxide.
- Acts as a buffer system.

One molecule of hemoglobin can bind to four oxygen atoms.
The binding of oxygen to hemoglobin is unstable and reversible.
Cooperative binding: Presence of one oxygen molecule on hemoglobin increases the affinity to bind more oxygen molecules.
Chloride shift: The movement of chloride ions (Cl-) across the red blood cell membrane to balance the charges during oxygen loading and unloading.
2,3-Diphosphoglycerate (2,3-DPG): A molecule that binds to deoxyhemoglobin and decreases its affinity for oxygen, promoting oxygen unloading in tissues.

Hb A (or HbA1): Normal adult hemoglobin, 97% of total hemoglobin.
Hb A2: Minor adult hemoglobin, 3% of total hemoglobin.
Hb F (Fetal hemoglobin): Main hemoglobin in newborns, 60% at birth. Gradually decreases with age.

Oxyhemoglobin: Hemoglobin bound to oxygen.
Deoxyhemoglobin: Hemoglobin after unloading oxygen.
Carbaminohemoglobin: Hemoglobin bound to carbon dioxide (CO2).
Glycosylated hemoglobin (HbA1c): Non-enzymatic glycation of hemoglobin, commonly used to monitor blood glucose levels in diabetes.
Carboxyhemoglobin: Hemoglobin bound to carbon monoxide (CO).
Methemoglobin: Hemoglobin with iron in its oxidized state (Fe³+), unable to bind oxygen.

Sickle Cell Anemia (Hb S disease):
- A point mutation in the beta-globin chain, where glutamic acid is replaced by valine.
- Can cause red blood cells to sickle, leading to anemia and other complications.
Hb C Disease:
- A point mutation in the beta-globin chain, where glutamic acid is replaced by lysine.
- Can cause red blood cell abnormalities but usually milder than sickle cell anemia.
Thalassemia: A genetic disorder characterized by reduced or absent production of alpha or beta-globin chains.
- Types based on the affected chain and severity:
  - Alpha-thalassemia: Reduced or absent alpha-globin chains.
  - Beta-thalassemia: Reduced or absent beta-globin chains.
  - Thalassemia minor: Heterozygous, milder form.
  - Thalassemia major: Homozygous, severe form.