## Introduction
This is the process of the origin, development and maturation of erythrocytes.
## Site
IN FETAL LIFE:
* Mesoblastic stage (1st two months of gestation): Primitive nucleated RBCs are produced in mesodermal cells of the yolk sac and mesothelial layers of the placenta
* Hepatic stage (from 3rd month of gestation): produced in the liver, then in the spleen and lymph nodes
* Myeloid stage (during the last three months of gestation): Red bone marrow and liver
NEWBORN BABIES TO ADULT (produced only from Red bone marrows)
* Up to 20 years of age: Red bone marrow of all bones
* After 20 years of age: Membranous bones e.g. vertebrae, sternum, ribs, iliac, scapula and skull bone and from the ends of long bones
Relative rates of red blood cell production in the bone marrow of different bones at different stages.
**DURATION**
* 5 days from Proerythroblast to reticulocyte
* 2-3 days from reticulocyte to maturation
**STAGES**
* Uncommitted Pluripotent Haematopoietic Stem Cells (PHSC)
* Colony Forming Unit–Erythrocyte (CFU-E)
* PROERYTHROBLAST (Megaloblast)
* EARLY NORMOBLAST (Basophil erythroblast)
* INTERMEDIATE NORMOBLAST (Polychromatophil erythroblast)
* LATE NORMOBLAST (Orthochromatophil erythroblast)
* Reticulocyte Erythrocyte (Mature RBC)
The blood cells begin their lives in the bone marrows from a type of cell called Pluripotent Haematopoietic Stem Cells (PHSC)
* **Uncommitted Pluripotent Haematopoietic Stem Cells (PHSC):** Differentiates into Colony Forming Unit–Erythrocyte (CFU-E) which is committed for the formation of RBCs.
* **Colony Forming Unit–Erythrocyte (CFU-E) [Committed stem cells]:** Develops into Proerythroblast.
* **Proerythroblast (Megaloblast):** Large cell with large nucleus having two or more nucleoli, and cytoplasm is basophilic in nature. The Proerythroblast do not contain haemoglobin. They divide multiple times, eventually forming the Basophil erythroblast.
* **Basophil erythroblast (Early normoblast):** Smaller than Proerythroblast, cytoplasm is basophilic in nature and stains with basic dye. Nucleoli disappear, chromatin network condenses. The cell at this time has accumulated very little haemoglobin. Develops into Polychromatophil erythroblast.
* **Polychromatophil erythroblast (Intermediate normoblast):** Smaller than early normoblast. Nucleus still present, but chromatin network further condenses. Cytoplasm, still basophilic, stains with both acidic and basic stains due to the presence of haemoglobin. This cell develops into the late normoblast.
* **Orthochromatophil erythroblast (late normoblast):** Cell diameter decreases, haemoglobin quantity increases and cytoplasm become acidophilic. Nucleus becomes very small and is eventually disintegrated and disappears. The final remnant is extruded from the cell. Late normoblast develops into reticulocyte.
* **Reticulocyte (Immature RBC):** Slightly larger than mature RBC. Cytoplasm is basophilic and contains reticular network formed by remnants of disintegrated organelles. After two days, reticulocytes diapedese from the bone marrow into the blood capillaries, circulate for about 24 hours, lose its basophilic material and becomes a mature erythrocyte. Reticulocyte stains with supravital stain.
* **Erythrocyte (mature RBC):** Reticular network has disappeared; cell attains biconcavity and lacks organelles.
| STAGES | EVENTS |
|———————|———————————|
| Proerythroblast | Protein synthesis starts |
| | Synthesis of haemoglobin starts |
| Early normoblast | Disappearance of nucleoli |
| Intermediate | Appearance of haemoglobin |
| normoblast | |
| Late normoblast | Disappearance of nucleus |
| Reticulocyte | Formation of reticulum |
| Mature erythrocytes | Reticulum disappears |
| ALL STAGES | |
Late normoblast Disappearance of nucleus
Reticulocyte Formation of reticulum
Mature erythrocytes Reticulum disappears
ALL STAGES
* Reduction in size of the cell
* Change in staining properties of cytoplasm
## Changes During Erythropoiesis Regulation
**GENERAL FACTORS**
* Erythropoietin (formation and release of RBCs into circulation)
* Thyroxine (accelerates erythropoiesis)
* Haemopoietic growth factors (induce proliferation of PHSCs – Interleukin-3, Interleukin-6 & Interleukin-11)
* Vitamins – Vitamin B, C, D & E
**MATURATION FACTORS (Responsible for maturation of RBCs)**
* Vitamin B12 (Cyanocobalamin) – synthesis of DNA in RBCs
* Folic acid – synthesis of DNA in RBCs
* Intrinsic factor – essential for absorption of Vitamin B12 from intestine
**FACTORS NECESSARY FOR HAEMOGLOBIN FORMATION**
* First class proteins and amino acids – synthesis of the protein part(globin) of haemoglobin
* Iron – formation of heme part of the haemoglobin
* Copper – necessary for the absorption of iron from the GIT
* Cobalt – essential for utilization of iron during haemoglobin formation
* Nickel – essential for utilization of iron during haemoglobin formation
* Manganese
* Vitamins – Vitamin C, riboflavin(Vitamin B2), pantothenic acid(Vitamin B5) pyridoxine(Vitamin B6) & nicotinic acid
**HORMONES**
* Growth Hormone (GH)
* Testosterone
* Cortisol
* Adrenocorticotropic hormone (ACTH)
* Thyroid Hormone (TH)
## Importance Of Erythropoiesis
* It allows for the availability of adequate red cells to provide sufficient transport of oxygen from the lungs to the tissues
* It helps in the compensation of blood during blood loss like in haemorrhage and menstruation
## Clinical Correlates
* Anemia: RBC disorder characterized by reduction in; RBC count Haemoglobin content Packed Cell Volume (PCV)
* Polycythaemia Vera
## Importance Of Erythropoiesis
It allows for the availability of adequate red cells to provide sufficient transport of oxygen from the lungs to the tissues. It helps in the compensation of blood during blood loss like in haemorrhage and menstruation.
## Clinical Correlates
* **Anaemia:** RBC disorder characterized by reduction in; RBC count, Haemoglobin content, Packed Cell Volume (PCV)
* **Polycythaemia Vera**
# Erythropoiesis
## Introduction
This is the process of the origin, development and maturation of erythrocytes.
## Site
**IN FETAL LIFE:**
* **Mesoblastic stage (1st two months of gestation):**
* Mesodermal cells of the yolk sac
* Mesothelial layers of the placenta
* **Hepatic stage (from 3rd month of gestation):**
* Liver
* Spleen
* Lymphoid tissues
* **Myeloid stage (last 3 month of gestation):**
* Red bone marrow
* Liver
**NEWBORN BABIES TO ADULT (only from the Red bone marrows)**
* **Up to 20 years of age:** Red bone marrow of all bones
* **After 20 years of age:** Membranous bones e.g. vertebrae, sternum, ribs, iliac, scapula and skull bone and from the ends of long bones. Relative rates of red blood cell production in the bone marrow of different bones at different stages.
**DURATION**
* 5 days from Proerythroblast to reticulocyte
* 2-3 days from reticulocyte to maturation
**STAGES**
* Uncommitted Pluripotent Haematopoietic Stem Cells (PHSC)
* Colony Forming Unit–Erythrocyte (CFU-E)
* PROERYTHROBLAST (Megaloblast)
* EARLY NORMOBLAST (Basophil erythroblast)
* INTERMEDIATE NORMOBLAST (Polychromatophil erythroblast)
* LATE NORMOBLAST (Orthochromatophil erythroblast)
* Reticulocyte
* Erythrocyte (Mature RBC)
**CHANGES DURING ERYTHROPOIESIS**
| STAGES | EVENTS |
|———————|———————————|
| Proerythroblast | Protein synthesis starts |
| | Synthesis of haemoglobin starts |
| Early normoblast | Disappearance of nucleoli |
| Intermediate | Appearance of haemoglobin |
| normoblast | |
| Late normoblast | Disappearance of nucleus |
| Reticulocyte | Formation of reticulum |
| Mature erythrocytes | Reticulum disappears |
| **ALL STAGES** | |
* Late normoblast: Disappearance of nucleus
* Reticulocyte: Formation of reticulum
* Mature erythrocytes: Reticulum disappears
**ALL STAGES**
* Reduction in size of the cell
* Change in staining properties of cytoplasm
## Regulation
**GENERAL FACTORS**
* Erythropoietin
* Thyroxine
* Haemopoietic growth factors (Interleukin-3, -6 & -11)
* Vitamins (B, C, D & E)
**MATURATION FACTORS**
* Vitamin B12
* Folic acid
* Intrinsic factor
**FACTORS NECESSARY FOR HAEMOGLOBIN FORMATION**
* First class proteins and amino acids – Globin synthesis
* Iron – Heme synthesis
* Copper
* Cobalt
* Nickel
* Manganese
* Vitamins (C, B2, B5, B6 & nicotinic acid)
**HORMONES**
* Growth Hormone
* Testosterone
* Cortisol
* Adrenocorticotropic hormone
* Thyroid Hormone
