Erythropoietin and RBC Production

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What is the function of red blood cells (erythrocytes) in the body?

Transport O2 to the tissues

What is the shape of red blood cells?

Biconcave discs

What is the average volume of red blood cells?

90-95 micrometers3

At higher altitudes, what happens to red blood cell counts?

Increase

Which parameter indicates the mean cell volume of red blood cells?

MCV

What does MCHC stand for and represent in terms of red blood cells?

Mean Cell Hemoglobin Concentration - indicates the Hgb concentration per cell

Which nutrient is present in green vegetables, some fruits, and meats?

Folic Acid

What can lead to a deficiency of folic acid?

Intestinal malabsorption

What might maturation failure indicate according to the text?

Combined B12 and folate deficiency

Which stage of RBC formation retains a small amount of endoplasmic reticulum and mRNA?

Reticulocyte stage

What is the predominant form of hemoglobin in adults?

Hemoglobin A

How many oxygen atoms can each hemoglobin molecule transport?

8 oxygen atoms

What is the role of erythropoietin in RBC production?

Drives the production of proerythroblasts from HSCs

Why is vitamin B12 important for cell proliferation?

It is needed to make thymidine triphosphate for DNA replication

What is a consequence of abnormal DNA replication due to lack of vitamin B12?

Failure of cell division

How does intrinsic factor help in vitamin B12 absorption?

Protects vitamin B12 from digestion and mediates its transport in the ileum

What is the usual duration for which normal stores of vitamin B12 are adequate?

3-4 years

How does erythropoietin level change once tissue oxygenation is restored?

It remains high

What is the main reason for regulating red blood cell mass within a narrow range?

To maintain adequate oxygen carrying capacity

In what condition may extramedullary hematopoiesis occur?

When the bone marrow is damaged or when there is extreme demand for erythropoiesis

What can result in red cell mass above the normal range?

Prolonged stay at high altitude

What stimulates Erythropoietin (EPO) production in response to hypoxia?

Epinephrine and norepinephrine

Where is approximately 90% of Erythropoietin (EPO) made in the body?

The kidney

In anephric individuals, where does the 10% residual EPO mainly come from?

Liver

What happens to hemoglobin released from senescent RBCs?

It is ingested by macrophages and stored as ferritin

Which organ secretes apotransferrin into the bile?

Liver

What is the function of transferrin in the body?

Binds to transferrin receptors on intestinal epithelium

What happens to RBCs as enzymes deplete with age?

They become fragile and rupture in small passages

How is iron absorbed in the body?

Throughout the small intestine

What is the daily iron loss in men and women, respectively?

~0.6 mg/day in men, ~1.3 mg/day in women

Study Notes

Folic Acid Deficiency

  • Folic acid is present in green vegetables, fruits, and meats.
  • Destroyed during cooking, and subject to dietary deficiencies.
  • Deficiencies may occur in cases of intestinal malabsorption.
  • Maturation failure may reflect combined B12 and folate deficiency.

Hemoglobin Formation

  • Occurs from proerythroblast through reticulocyte stage.
  • Reticulocytes retain a small amount of endoplasmic reticulum and mRNA, supporting continued hemoglobin synthesis.

Hemoglobin Structure

  • Consists of four subunits: α, β, γ, δ.
  • Each globin chain is associated with one heme group containing one atom of iron.
  • Each hemoglobin molecule can transport 8 oxygen atoms.

Response to Hypoxia

  • Erythropoietin production increases within minutes to hours.
  • New circulating reticulocytes appear in ~3 days.
  • Erythropoietin drives production of proerythroblasts from HSCs and accelerates their maturation into RBCs.
  • Can increase RBC production up to 10-fold.

Vitamin B12 and Folic Acid

  • Required for DNA replication and cell proliferation.
  • Abnormal DNA replication causes failure of nuclear maturation and cell division, leading to fragile "macrocytes".

Pernicious Anemia

  • Failure to absorb vitamin B12 due to atrophic gastric mucosa and lack of intrinsic factor.
  • Vitamin B12 is stored in the liver and released as needed.

Red Blood Cells (Erythrocytes)

  • Carry hemoglobin, bearing oxygen to the tissues.
  • Contain carbonic anhydrase, which catalyzes the reaction: CO2 + H2O → H2CO3.
  • Hemoglobin is an excellent acid-base buffer.

RBC Size and Shape

  • Biconcave discs with a mean size of 7.8 x 2.5 microns (thickest) or x 1 micron (center).
  • Average volume is 90-95 micrometers3.

RBC Count and Indices

  • Men: 5,200,000 (± 300,000) / mm3.
  • Women: 4,700,000 (± 300,000) / mm3.
  • RBC indices: MCV, MCH, MCHC, and RDW.

Regulation of Red Cell Mass

  • Red blood cell mass is regulated to maintain adequate oxygen carrying capacity and avoid excessive blood viscosity.

Tissue O2 and Erythropoietin

  • Hypoxia stimulates erythropoietin production, leading to increased RBC production.

Erythropoietin (EPO)

  • Circulating hormone necessary for erythropoiesis in response to hypoxia.
  • 90% produced in the kidneys, with some production in the liver.

Iron Balance

  • Daily iron loss: 0.6 mg/day in men, 1.3 mg/day in women.
  • Iron is absorbed throughout the small intestine, stored in the liver, and transported by transferrin.

RBC Senescence & Destruction

  • RBC life span is ~120 days.
  • As enzymes deplete with age, RBCs become fragile and rupture in small passages, often in the spleen.

Learn about the role of erythropoietin in stimulating the production of red blood cells (RBCs) and how it can increase RBC production up to 10-fold. Explore how Vitamin B12 and Folic Acid are essential for rapid and large-scale cellular proliferation.

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