02/02/2026
RED BLOOD CELLS (RBCs)
Synthesis, Functions, and Excretion (Destruction)
1. Introduction
Red Blood Cells (Erythrocytes) are specialized, anucleate cells whose primary role is gas transport.
They contain hemoglobin, which enables oxygen and carbon dioxide transport.
Normal lifespan: ~120 days
Normal count:
Male: ~4.5–6.0 million/µL
Female: ~4.0–5.5 million/µL
2. RBC Synthesis (Erythropoiesis)
Definition
Erythropoiesis is the process of production and maturation of RBCs from stem cells.
Site
Bone marrow (flat bones in adults: pelvis, sternum, ribs, vertebrae)
During fetal life:
Yolk sac → Liver → Spleen → Bone marrow
Stages of Erythropoiesis (Very Important)
Pluripotent Hematopoietic Stem Cell
Myeloid Stem Cell
Proerythroblast
Basophilic Erythroblast
Polychromatophilic Erythroblast
Orthochromatic Erythroblast (Normoblast)
Nucleus is extruded here
Reticulocyte
Enters peripheral blood
Mature Erythrocyte
📌 Reticulocyte matures into RBC within 1–2 days in circulation.
Regulation of RBC Production
1️⃣ Erythropoietin (EPO)
Hormone produced mainly by kidneys
Released in response to hypoxia
Stimulates bone marrow to increase RBC production
📌 Chronic kidney disease → ↓ EPO → anemia
Requirements for Normal RBC Synthesis
Requirement
Role
Iron
Hemoglobin synthesis
Vitamin B₁₂
DNA synthesis
Folic acid
DNA synthesis
Protein
Globin chain formation
Vitamin B₆
Heme synthesis
Healthy bone marrow
Cell production
Functional kidneys
EPO production
📌 Deficiency → anemia (iron deficiency, megaloblastic anemia, etc.)
3. Structure of Mature RBC
Shape: Biconcave disc
Diameter: ~7–8 µm
No nucleus, no mitochondria
Flexible membrane → passes through capillaries
Energy source: Anaerobic glycolysis
📌 Lack of nucleus allows more space for hemoglobin.
4. Functions of RBCs
1️⃣ Oxygen Transport
Hemoglobin binds oxygen in lungs
Releases oxygen to tissues
One RBC can carry millions of oxygen molecules via hemoglobin
2️⃣ Carbon Dioxide Transport
CO₂ transported in three forms:
Bicarbonate (major)
Carbaminohemoglobin
Dissolved CO₂
3️⃣ Acid–Base Balance
Hemoglobin acts as a buffer
Maintains blood pH (~7.35–7.45)
4️⃣ Nitric Oxide Regulation
RBCs influence vascular tone and blood flow
5. RBC Aging and Destruction (Excretion Process)
Lifespan
RBCs circulate for ~120 days
Aging leads to:
↓ membrane flexibility
↓ enzyme activity
Site of Destruction
Mainly extravascular hemolysis in:
Spleen (major site)
Liver
Bone marrow
📌 Spleen = “graveyard of RBCs”
6. Breakdown of RBC Components
A. Globin Portion
Broken into amino acids
Reused for protein synthesis
B. Heme Portion
Step 1: Heme → Biliverdin
Enzyme: Heme oxygenase
Releases:
Iron (Fe³⁺)
Carbon monoxide (CO)
Step 2: Biliverdin → Bilirubin
Enzyme: Biliverdin reductase
Forms unconjugated bilirubin
Insoluble in water
Transported bound to albumin
7. Bilirubin Metabolism (Excretion Pathway)
In the Liver
Unconjugated bilirubin enters hepatocytes
Conjugated with glucuronic acid
Enzyme: UDP-glucuronyl transferase
Becomes conjugated (direct) bilirubin
In the Intestine
Conjugated bilirubin → urobilinogen
Fates:
Oxidized to stercobilin → f***s (brown color)
Reabsorbed → urobilin → urine (yellow color)
Small amount returns to liver (enterohepatic circulation)
8. Iron Recycling
Iron released from heme:
Stored as ferritin / hemosiderin
Transported by transferrin
Reused for new RBC synthesis
📌 Efficient recycling → daily iron loss is minimal
9. Clinical Correlations (Lab-Oriented)
Increased RBC Destruction
Hemolytic anemia
↑ Unconjugated bilirubin
↑ Reticulocyte count
↓ Haptoglobin
Decreased RBC Production
Iron deficiency anemia
Aplastic anemia
Chronic kidney disease
Vitamin B₁₂ / folate deficiency
10. One-Page Memory Flow 🧠
Bone marrow → RBC → Circulation (120 days) → Spleen → Heme → Bilirubin → Liver → Bile → Stool & Urine
