Blood-RBC&Anaemia I 2025

RBC and Anaemia (Introduction)

Basic Concepts

• Compositions of Blood: Blood is a complex tissue composed of plasma and various cellular components, including red blood cells, white blood cells, and platelets, all of which play critical roles in maintaining physiological functions.

• Haemopoiesis: The highly regulated process of blood cell formation, occurring mainly in the bone marrow in adults. This involves the proliferation and differentiation of haematopoietic stem cells into mature blood cells.

• Types of Anaemias:

  • General: A reduction in the number of red blood cells or hemoglobin in the blood, leading to decreased oxygen-carrying capacity and subsequent tissue hypoxia.

  • Iron Deficiency: A common form of anemia resulting from inadequate iron levels required for hemoglobin synthesis. This can be due to insufficient dietary intake, impaired absorption, or increased iron loss.

  • Vitamin B12 & Folate Deficiency: Anemia caused by a lack of vitamin B12 or folate, both of which are essential for DNA synthesis in red blood cell precursors. Deficiencies lead to impaired cell division and the production of abnormally large red blood cells (megaloblasts).

Learning Outcomes

• Comprehend the process of haemopoiesis and its regulation under normal conditions and in various pathological states, including the role of growth factors and cytokines.

• Gain insights into the pathogenesis, clinical features, and biochemical markers related to anaemias, specifically those due to iron, vitamin B12, and folate deficiencies, understanding their impact on red blood cell production and function.

Blood and Cellular Components

• Blood Functions:

  • Transport: Oxygen is distributed from the lungs to tissues via hemoglobin in red blood cells, while carbon dioxide is transported back for exhalation. Blood also transports nutrients from the digestive system to cells, hormones from endocrine glands to target tissues, and waste products from cells to excretory organs.

  • Immune Response: White blood cells, including neutrophils, lymphocytes, monocytes, eosinophils, and basophils, are crucial for immune defense against pathogens, enabling the body to recognize and neutralize foreign invaders.

• Blood Composition:

  • Plasma: Comprises approximately 55% of blood volume, consisting of water, electrolytes (sodium, potassium, chloride), proteins (albumin, globulins, clotting factors), hormones, nutrients (glucose, amino acids, lipids), and waste products (urea, creatinine, bilirubin).

  • Cells: Approximately 40-45% of blood volume, consisting of various cells that perform specific functions, including oxygen transport, immune defense, and blood clotting.

Types of Cells:

• Red Blood Cells (Erythrocytes): Specialized cells that carry oxygen from the lungs to tissues via hemoglobin, a protein containing iron. Their unique biconcave shape maximizes surface area for efficient gas exchange.

• White Blood Cells (Leucocytes): A diverse group of cells involved in immune responses, including neutrophils (phagocytosis), lymphocytes (adaptive immunity), monocytes (differentiate into macrophages), eosinophils (parasitic infections and allergies), and basophils (inflammatory responses).

• Platelets (Thrombocytes): Small, anucleate cell fragments essential for blood clotting. They aggregate at the site of blood vessel injury to form a platelet plug and initiate the coagulation cascade.

Haemopoiesis

• Site of Production:

  • Initiation occurs in the yolk sac around the 3rd week of gestation, providing early blood cells for the developing embryo.

  • Liver and spleen are responsible from 6 weeks to 6 months during fetal development (extramedullary haemopoiesis), serving as primary sites of blood cell production before bone marrow development.

  • The bone marrow becomes the primary site from 6 months until birth and continues in adults, housing haematopoietic stem cells that differentiate into all blood cell types.

  • Extramedullary Haemopoiesis: May occur under pathological conditions, such as chronic anemia or certain malignancies, when the bone marrow is unable to meet the body's demands for blood cell production.

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 (neutrophils, eosinophils, basophils, monocytes). These cells are responsible for oxygen transport, blood clotting, and innate immune responses.

  • Lymphoid Stem Cells: Lead to T and B lymphocytes, which are critical for adaptive immunity, including antibody production and cell-mediated immunity.

  • Committed stem cells undergo changes to become recognisable precursors of mature blood cells. These precursors undergo further differentiation and maturation, involving changes in cell size, shape, and function.

Peripheral Blood Smears

• Cell Types Identified in Smears:

  • Erythrocytes (A): The primary oxygen transporters, appearing as biconcave discs without a nucleus. Their morphology is critical for assessing various anemias.

  • White Blood Cells: Includes lymphocytes (B, H), neutrophils (C, E, I), eosinophils (D), monocytes (F), and basophils (J), each with distinct morphological features and functions in immune defense.

  • Thrombocytes (G): Small, anucleate cell fragments that play a crucial role in hemostasis, forming platelet plugs and initiating the coagulation cascade.

Red Blood Cell (RBC) Characteristics

• Average Diameter: 7-8 μm, biconcave structure enhances surface area for gas exchange, allowing efficient oxygen and carbon dioxide transport.

Normal Red Cell Values:

• RBC Count: 4.5 - 6.5 million cells/µL (male), 3.9 - 5.6 million cells/µL (female); these values reflect the number of red blood cells per unit volume of blood.

• Hemoglobin: 13.8 - 17.5 g/dL (male), 11.3 - 15.5 g/dL (female); hemoglobin is the protein in red blood cells that carries oxygen, and its concentration is a key indicator of oxygen-carrying capacity.

• PCV% (Hematocrit): 40 - 52% (male), 36 - 48% (female); hematocrit represents the percentage of blood volume occupied by red blood cells.

• Reticulocytes: Approximately 1% of total RBC count, indicates bone marrow activity, reflecting the rate of red blood cell production.

RBC Derived Absolute Values:

• Mean Cell Volume (MCV): Measures the average size of red blood cells, normal range 80-95 fL, used to classify anemias as microcytic, normocytic, or macrocytic.

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

• Mean Cell Hemoglobin Concentration (MCHC): Average concentration of hemoglobin in a given volume of packed red cells, normal range 32-36 g/dL, used to classify anemias as hypochromic, normochromic, or hyperchromic.

Erythropoiesis

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

  • Stem cell → Proerythroblast → Erythroblast (early, late) → Normoblast (early, late) → Reticulocyte → Erythrocyte. This maturation process involves multiple stages of cell division and differentiation.

  • Occurs primarily in the bone marrow with the final transition to the peripheral blood, where reticulocytes mature into erythrocytes, losing their ribosomes.

Features of Erythropoiesis

• Processes: Involves multiple stages of mitosis and maturation leading to reticulocyte formation, driven by erythropoietin, a hormone produced by the kidneys in response to hypoxia.

• Key Factors: Essential nutrients like iron, vitamin B12, and folic acid are critical for normal erythropoiesis, serving as cofactors for enzymes involved in DNA synthesis and hemoglobin production.

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, leading to decreased oxygen delivery to tissues.

• Classification:

  • Hypochromic Microcytic: Low MCV, often associated with iron deficiency, resulting in small and pale red blood cells.

  • Normochromic Normocytic: Normal MCV, seen in various conditions including acute blood loss, where red blood cells are normal in size and hemoglobin content.

  • Macrocytic: High MCV, typically associated with vitamin B12 or folate deficiency, leading to large red blood cells (megaloblasts).

Pathological Consequences

• Anaemia often leads to tissue hypoxia, impairing the function of organs and systems, resulting in fatigue, weakness, and other symptoms.

Clinical Manifestations of Anaemia

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

• Signs: Pallor, especially notable in the conjunctiva of the eyes, nail beds, and mucous membranes.

Laboratory Investigation for Anaemia

• Indicative Blood Values: Reduced values of RBC count, hemoglobin, and PCV, indicating a decrease in red blood cell mass and oxygen-carrying capacity.

• Blood Film Indicators:

  • Anisocytosis: Variation in cell size, reflecting abnormal red blood cell production.

  • Poikilocytosis: Variation in cell shape, indicating underlying red blood cell disorders.

  • Anisochromasia: Variation in hemoglobinization, suggesting uneven hemoglobin distribution in red blood cells.

Causes of Anaemia

• Categories of Causes:

  • Decreased Production: Examples include aplastic anemia (bone marrow failure) or bone marrow disorders (myelodysplastic syndromes), leading to reduced red blood cell production.

  • Increased Destruction/Loss: Examples include hemorrhages (acute or chronic blood loss) or hemolysis (destruction of red blood cells), resulting in decreased red blood cell survival.

Iron Deficiency Anaemia

• Characteristics: Microcytic, hypochromic red blood cells; most common cause of anemia worldwide, resulting from insufficient iron for hemoglobin synthesis.

• Iron Metabolism:

  • Absorption is primarily regulated and requires gastric HCl for conversion of iron from Fe^{3+} to Fe^{2+}, enhancing its absorption in the duodenum.

  • Iron stores are found in the body as ferritin and haemosiderin, and it is transported by transferrin, ensuring iron is available for erythropoiesis.

• Mechanisms of Iron Deficiency:

  • Increased demands (e.g., pregnancy, growth spurts), chronic blood loss (menstruation, gastrointestinal bleeding), poor dietary intake, or malabsorption syndromes (celiac disease, gastrectomy).

Treatment for Iron Deficiency Anaemia

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

• Monitoring: Regularly monitor reticulocyte count and hemoglobin levels to assess treatment effectiveness, ensuring adequate response to iron supplementation.

Failure to Respond to Iron Therapy

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

Megaloblastic Anaemia

• Characteristics: Macrocytic with normo/hypochromic features, presence of megaloblasts in the bone marrow, reflecting impaired DNA synthesis in red blood cell precursors.

• Peripheral Blood Features: Large oval erythrocytes, presence of Howell-Jolly bodies (DNA remnants), and hypersegmented neutrophils (more than five lobes).

Causes of Megaloblastic Anaemia

• Often due to deficiencies in vitamin B12 and folate, leading to disruptions in DNA synthesis and cell maturation, causing abnormal red blood cell development.

Biochemical Implications

• DNA Synthesis Block: There is a conversion pathway involving deoxyuridine monophosphate (dUMP) and methylene tetrahydrofolate that is disrupted in these conditions, leading to impaired DNA synthesis.

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, preventing the accumulation of abnormal DNA precursors.

Causes of Vitamin B12 Deficiency

• Low dietary intake (vegans), malabsorption due to pernicious anemia (autoimmune destruction of parietal cells), gastrectomy, Crohn's disease, and other gastrointestinal conditions, leading to inadequate vitamin B12 absorption.

Folate Deficiency

• Sources: Found in high concentrations in meats and green vegetables; usually in polyglutamate forms, which must be converted to monoglutamate for absorption.

• Metabolism: Converted to monoglutamate for absorption in the intestines, requiring the enzyme glutamate carboxypeptidase II.

Causes of Folate Deficiency

• Nutritional causes (poor diet), malabsorption syndromes (celiac disease), 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.