Blood-RBC&Anaemia I 2025

RBC and Anaemia (Introduction)

Basic Concepts

• Compositions of Blood: Blood is composed of plasma and various cellular components that play critical roles in physiological functions.

• Haemopoiesis: The process of blood cell formation.

• Types of Anaemias:

  • General: A reduction in the number of red blood cells or hemoglobin leading to decreased oxygen transport.

  • Iron Deficiency: A common form of anemia resulting from inadequate iron levels.

  • Vitamin B12 & Folate Deficiency: Anemia caused by a lack of vitamin B12 or folate necessary for red blood cell formation.

Learning Outcomes

• Comprehend the process of haemopoiesis and its regulation under normal conditions and in various pathological states.

• Gain insights into the pathogenesis, clinical features, and biochemical markers related to anaemias, specifically those due to iron, vitamin B12, and folate deficiencies.

Blood and Cellular Components

• Blood Functions:

  • Transport: Oxygen is distributed from the lungs to tissues, while carbon dioxide is transported back for exhalation. Nutrients and waste products are also exchanged.

  • Immune Response: White blood cells are crucial for immune defense against pathogens.

• Blood Composition:

  • Plasma: Comprises approximately 55% of blood and contains water, electrolytes, proteins, hormones, and waste products.

  • Cells: Approximately 40-45% of blood volume, consisting of various cells that perform specific functions.

Types of Cells:

• Red Blood Cells (Erythrocytes): Carry oxygen via hemoglobin.

• White Blood Cells (Leucocytes): Involved in immune responses.

• Platelets (Thrombocytes): Essential for blood clotting.

Haemopoiesis

• Site of Production:

  • Initiation occurs in the yolk sac around the 3rd week of gestation.

  • Liver and spleen are responsible from 6 weeks to 6 months during fetal development (extramedullary haemopoiesis).

  • The bone marrow becomes the primary site from 6 months until birth and continues in adults.

  • Extramedullary Haemopoiesis: May occur under pathological conditions, such as chronic anemia or certain malignancies.

Blood Cell Differentiation

• Stem Cell Lineage: Pluripotential stem cells differentiate into:

  • Myeloid Stem Cells: Lead to red blood cells, platelets, and some white blood cells.

  • Lymphoid Stem Cells: Lead to T and B lymphocytes.

  • Committed stem cells undergo changes to become recognisable precursors of mature blood cells.

Peripheral Blood Smears

• Cell Types Identified in Smears:

  • Erythrocytes (A): The primary oxygen transporters.

  • White Blood Cells: Includes lymphocytes (B, H), neutrophils (C, E, I), eosinophils (D), monocytes (F), and basophils (J).

  • Thrombocytes (G): Play a role in hemostasis.

Red Blood Cell (RBC) Characteristics

• Average Diameter: 7-8 μm, biconcave structure enhances surface area for gas exchange.

Normal Red Cell Values:

• RBC Count: 4.5 - 6.5 million cells/µL (male), 3.9 - 5.6 million cells/µL (female)

• Hemoglobin: 13.8 - 17.5 g/dL (male), 11.3 - 15.5 g/dL (female)

• PCV% (Hematocrit): 40 - 52% (male), 36 - 48% (female)

• Reticulocytes: Approximately 1% of total RBC count, indicates bone marrow activity.

RBC Derived Absolute Values:

• Mean Cell Volume (MCV): Measures the average size of red blood cells, normal range 80-95 fL.

• Mean Cell Hemoglobin (MCH): Average amount of hemoglobin per red blood cell, normal range 27-32 pg.

• Mean Cell Hemoglobin Concentration (MCHC): Average concentration of hemoglobin in a given volume of packed red cells, normal range 32-36 g/dL.

Erythropoiesis

• Stages of Formation: Sequential differentiation from stem cells to mature erythrocytes:

  • Stem cell → Proerythroblast → Erythroblast (early, late) → Normoblast (early, late) → Reticulocyte → Erythrocyte.

  • Occurs primarily in the bone marrow with the final transition to the peripheral blood.

Features of Erythropoiesis

• Processes: Involves multiple stages of mitosis and maturation leading to reticulocyte formation, driven by erythropoietin.

• Key Factors: Essential nutrients like iron, vitamin B12, and folic acid are critical for normal erythropoiesis.

Definition of Anaemia

• Anaemia is defined as having hemoglobin levels below the reference threshold for age and gender, indicating a reduction in red cell mass.

• Classification:

  • Hypochromic Microcytic: Low MCV, often associated with iron deficiency.

  • Normochromic Normocytic: Normal MCV, seen in various conditions including acute blood loss.

  • Macrocytic: High MCV, typically associated with vitamin B12 or folate deficiency.

Pathological Consequences

• Anaemia often leads to tissue hypoxia, impairing the function of organs and systems.

Clinical Manifestations of Anaemia

• Symptoms: Often asymptomatic at mild levels; more severe levels present symptoms like fatigue, headaches, and faintness.

• Signs: Pallor, especially notable in the conjunctiva of the eyes.

Laboratory Investigation for Anaemia

• Indicative Blood Values: Reduced values of RBC count, hemoglobin, and PCV.

• Blood Film Indicators:

  • Anisocytosis: Variation in cell size.

  • Poikilocytosis: Variation in cell shape.

  • Anisochromasia: Variation in hemoglobinization.

Causes of Anaemia

• Categories of Causes:

  • Decreased Production: Examples include aplastic anemia or bone marrow disorders.

  • Increased Destruction/Loss: Examples include hemorrhages or hemolysis.

Iron Deficiency Anaemia

• Characteristics: Microcytic, hypochromic red blood cells; most common cause of anemia worldwide.

• Iron Metabolism:

  • Absorption is primarily regulated and requires gastric HCl for conversion of iron from Fe+++ to Fe++.

  • Iron stores are found in the body as ferritin and haemosiderin, and it is transported by transferrin.

• Mechanisms of Iron Deficiency:

  • Increased demands (e.g., pregnancy), chronic blood loss, poor dietary intake, or malabsorption syndromes.

Treatment for Iron Deficiency Anaemia

• Management: Identify and treat underlying causes; oral iron supplements are typical for replenishing stores.

• Monitoring: Regularly monitor reticulocyte count and hemoglobin levels to assess treatment effectiveness.

Failure to Respond to Iron Therapy

Potential reasons might include non-compliance, misdiagnosis (such as thalassemia trait), mixed deficiencies, chronic inflammatory states, or malignancies.

Megaloblastic Anaemia

• Characteristics: Macrocytic with normo/hypochromic features, presence of megaloblasts in the bone marrow.

• Peripheral Blood Features: Large oval erythrocytes, presence of Howell-Jolly bodies, and hypersegmented neutrophils.

Causes of Megaloblastic Anaemia

• Often due to deficiencies in vitamin B12 and folate, leading to disruptions in DNA synthesis and cell maturation.

Biochemical Implications

• DNA Synthesis Block: There is a conversion pathway involving deoxyuridine monophosphate and methylene tetrahydrofolate that is disrupted in these conditions.

Vitamin B12 Deficiency

• Found predominantly in animal products; not present in plants. It requires Intrinsic Factor for absorption in the terminal ileum and is critical for proper methylation and DNA synthesis.

Causes of Vitamin B12 Deficiency

• Low dietary intake, malabsorption due to pernicious anemia, gastrectomy, Crohn's disease, and other gastrointestinal conditions.

Folate Deficiency

• Sources: Found in high concentrations in meats and green vegetables; usually in polyglutamate forms.

• Metabolism: Converted to monoglutamate for absorption in the intestines.

Causes of Folate Deficiency

• Nutritional causes, malabsorption syndromes, increased utilization (as seen in pregnancy or malignancies), and drug influences (e.g., alcohol, anticonvulsants).

Erythropoiesis Quiz

• Identify which statement is NOT true regarding erythropoiesis to test comprehension.

Anaemia Quiz

• Identify the causes of anaemia from provided options to reinforce learning and application of knowledge.