Hematology and Related Disorders

Introduction to Hematology

Hematology is the study of blood, its components, and related disorders. Blood is a vital connective tissue responsible for transport, regulation, and protection within the body. Understanding its composition and function is essential for diagnosing and managing hematologic diseases.

• Blood Volume: Average adult blood volume is 5-6 liters.

• Composition: 90% water, 8% proteins (albumin, globulins, fibrinogen), 2% hormones, electrolytes, and enzymes.

• Cellular Components: Red blood cells (RBCs), white blood cells (WBCs), and platelets (thrombocytes).

Composition and Function of Blood

Plasma

Plasma is the liquid portion of blood, serving as a medium for transporting nutrients, hormones, and waste products.

• Transport: Carries nutrients, hormones, oxygen (via RBCs), and waste products.

• Temperature Regulation: Distributes heat throughout the body.

Plasma Proteins

Plasma proteins play crucial roles in maintaining blood volume, transport, and immunity.

• Albumin: Maintains oncotic pressure and blood volume.

• Alpha and Beta Globulins: Transport substances such as bilirubin, steroids, and iron.

• Gamma Globulins: Function as antibodies in the immune system.

• Fibrinogen: Initiates blood coagulation and clot formation.

Blood Cells

Blood contains three main types of cells, each with specialized functions.

• Erythrocytes (RBCs): Transport oxygen and carbon dioxide, maintain acid-base balance, and contain hemoglobin.

• Leukocytes (WBCs): Defend against infection and participate in immune responses.

• Thrombocytes (Platelets): Essential for blood clotting and hemostasis.

Formation and Life Cycle of Blood Cells

Hematopoiesis

Blood cells are produced in the bone marrow through a process called hematopoiesis, regulated by growth factors and cytokines.

• Growth Factors: GM-CSF, G-CSF, EPO (erythropoietin), TPO (thrombopoietin), and various interleukins.

• Stem Cells: Differentiate into RBCs, WBCs, and platelets.

Erythrocyte Life Cycle

Red blood cells have a lifespan of approximately 120 days. They are produced in the bone marrow, circulate in the blood, and are eventually removed by the spleen.

• Hemoglobin: Each RBC contains about 270 million hemoglobin molecules, each with 2 alpha and 2 beta chains and iron (Fe).

• Function: Oxygen transport, carbon dioxide removal, and acid-base balance.

Laboratory Values in Hematology

Common Laboratory Values

Laboratory tests are essential for diagnosing hematologic disorders. Reference ranges vary by age and sex.

Additional info: RDW (Red Cell Distribution Width) indicates variation in RBC size; MCV (Mean Corpuscular Volume) reflects average RBC size.

Hematology Disorders

Anemia

Anemia is defined as a reduction in RBC mass or hemoglobin concentration, leading to decreased oxygen-carrying capacity.

• Symptoms: Fatigue, pallor, tachycardia, dizziness, and shortness of breath.

• Types: Iron deficiency anemia, megaloblastic anemia (B12 and folate deficiency), hemolytic anemia, and anemia of chronic disease.

Iron Deficiency Anemia

Iron deficiency anemia results from insufficient iron, impairing hemoglobin synthesis and RBC production.

• Causes: Blood loss, poor dietary intake, malabsorption, increased requirements (e.g., pregnancy).

• Clinical Features: Pallor, fatigue, glossitis, spoon-shaped nails (koilonychia), pica (craving non-food substances).

Iron Physiology and Lifecycle

Iron is essential for hemoglobin synthesis, mitochondrial function, and neurotransmitter production.

• Absorption: Occurs in the duodenum via enterocytes; regulated by hepcidin and ferroportin.

• Transport: Iron is transported in plasma bound to transferrin.

• Storage: Stored in the liver as ferritin.

Iron Deficiency Mechanisms:

• Absolute deficiency: Low intake, increased loss, or impaired absorption.

• Functional deficiency: Adequate stores but impaired mobilization (e.g., chronic inflammation).

Megaloblastic Anemias

Megaloblastic anemias are caused by impaired DNA synthesis due to vitamin B12 or folate deficiency, resulting in large, immature RBCs.

• Vitamin B12 Deficiency: Requires intrinsic factor for absorption; deficiency leads to neurologic symptoms (paresthesias, demyelination).

• Folate Deficiency: Often due to poor intake, increased demand, or malabsorption.

• Clinical Features: Glossitis, neuropsychiatric symptoms, pancytopenia.

Hemolytic Anemias

Hemolytic anemias result from increased destruction of RBCs, either intravascularly or extravascularly.

• Sickle Cell Disease: Mutation in the beta chain of hemoglobin (valine substitution); causes sickling, vaso-occlusion, and hemolysis.

• Thalassemias: Defective synthesis of alpha or beta globin chains; leads to microcytic, hypochromic anemia and bone marrow expansion.

• G6PD Deficiency: Enzyme defect causing oxidative damage and hemolysis, often triggered by drugs or infections.

• Acquired Hemolytic Anemias: Caused by toxins, autoimmune reactions, or transfusion incompatibility.

Polycythemia

Definition and Types

Polycythemia is characterized by increased RBC mass. It may be primary (polycythemia vera) or secondary (compensatory response to hypoxia).

• Primary Polycythemia: Myeloproliferative disorder with increased RBC, WBC, and platelets.

• Secondary Polycythemia: Due to chronic hypoxia (e.g., lung disease, high altitude).

• Relative Polycythemia: Decreased plasma volume with normal RBC mass.

Summary Table: Anemia Laboratory Findings

Key Equations

• Oxygen Saturation Curve: Relationship between PO2 and hemoglobin saturation is sigmoidal.

• Mean Corpuscular Volume (MCV):

• Mean Corpuscular Hemoglobin (MCH):

• Mean Corpuscular Hemoglobin Concentration (MCHC):

Clinical Applications

• Diagnosis: Laboratory values and clinical presentation guide diagnosis of hematologic disorders.

• Treatment: Iron supplementation for iron deficiency, vitamin B12 or folate for megaloblastic anemia, and specific therapies for hemolytic anemias.

Additional info: Iron absorption is enhanced by vitamin C and impaired by gastric acid suppression; chronic inflammation increases hepcidin, reducing iron availability.