Untitled Quiz

Structure and Function of the Hematologic System

• Learning Objectives: Students will compare and contrast various hematologic disorders, including etiology, pathogenic mechanisms, altered morphology/physiology, signs/symptoms, genetic/environmental factors, and complications. Students will also examine risk factors. Specific disorders listed include iron deficiency anemia, megaloblastic anemias, hemolytic anemias (ex. sickle cell anemia), Hodgkin/Non-Hodgkin Lymphomas, acute and chronic myelogenous leukemia, multiple myeloma, thrombocytopenia, thrombocytosis, qualitative platelet disorders, and coagulation disorders (clotting factor deficiencies and DIC).

• Functions of the Hematologic System: Delivering substances for cellular metabolism, removing waste products, defending against microorganisms and injury, and maintaining acid-base balance.

• Composition of Blood: Consists of 91% water and 9% solutes (6 quarts or 5.5 liters). Cellular components comprise 45% of the blood volume, and plasma accounts for 50-55%. Plasma contains organic and inorganic elements and plasma proteins (including albumins, globulins, and clotting factors, mainly fibrinogen). Globulins are carriers and immunoglobulins.

• Cellular Components:

  • Erythrocytes (Red Blood Cells): Most abundant blood cells, responsible for tissue oxygenation. They are biconcave and lack a nucleus and cytoplasmic organelles, with a lifespan of 120 days.
  • Leukocytes (White Blood Cells): Defend against infection and remove debris. Granulocytes (containing granules) have inflammatory and immune functions and can move by ameboid movement (diapedesis). Specific examples of granulocytes include neutrophils (60-70%), eosinophils (2-4%), and basophils (0.5-1%). Mast cells are functionally and structurally similar to basophils.
  • Agranulocytes: These include monocytes (immature macrophages, 3-8%), macrophages (monocytes in tissues), lymphocytes (including T cells, B cells, plasma cells, and natural killer [NK] cells, accounting for 20-25%), and platelets (disk-shaped cytoplasmic fragments of megakaryocytes, essential for blood clotting).

• Lymphoid Organs: Include primary organs (thymus and bone marrow), and secondary organs (spleen, lymph nodes).

  • Spleen: Largest secondary lymphoid organ, with splenic pulp containing lymphoid tissue, macrophages, and venous sinuses. It plays a role in phagocytosis of old/damaged blood cells and blood storage (300 ml). Involved in immune and hematologic systems.
  • Lymph Nodes: Part of the immune and hematologic systems, assisting with maturation of lymphocytes, transportation of lymphatic fluid back to the circulation, and cleansing of lymphatic fluid for microorganisms and foreign particles.

• Hematopoiesis: The process of blood cell production, occurring in two stages: mitosis (proliferation), and maturation and differentiation.

• Bone Marrow: Contains red (active) and yellow (inactive) marrow. Red marrow is the source for blood cell production in adults and is located in pelvic bones, vertebrae, cranium/mandible, sternum/ribs, and humerus/femur.

• Blood Cell Maturation: The process can be visualized by diagrams illustrating the different types and stages of blood cells during development. Information about specific and distinct cells include Myeloblast, Promyelocyte, Myelocyte, Metamyelocyte, Band, Basophil, Eosinophil, Neutrophil, Monocyte, Megakaryocytes, Platelets, Erythrocytes, and Lymphocytes.

• Erythropoiesis: The specific process of red blood cell production. Key player is erythropoietin (EPO), produced by peritubular cells of the kidney, which is stimulated by hypoxia. Erythropoiesis involves different stages that mature from a stem cell to a committed proerythroblast, then normoblasts or reticulocytes to an erythrocyte.

• Hemoglobin: Oxygen-carrying protein. A single erythrocyte contains up to 300 hemoglobin molecules. Four colorful iron-protoporphyrin complexes in each hemoglobin molecule bind to one molecule of oxygen. Iron is necessary and is found in hemoglobin.

• Hemoglobin Synthesis: Requires specific building blocks (proteins and specific amino acids) and vitamins (B12, B6, B2, E, C, folic acid, and pantothenic acid, and niacin), and minerals (iron and copper).

• Normal Destruction of Senescent Erythrocytes: Aged red blood cells are broken down by macrophages (MPS) in the spleen (primary). The liver takes over if the spleen isn't functional. Globin chains are broken down into amino acids and porphyrin is reduced to bilirubin which is transported to the liver for secretion in the bile.

• Development of Leukocytes and Platelets: Stem cells produce different types of these cells in the bone marrow. Leukocytes (and their maturation) are encouraged by growth factors and colony-stimulating factors. Production also increases when there is infection, release of steroids, increased heart rate, pain, or nausea/vomiting. Platelet production and maintenance are dependent on thrombopoietin and IL-11. Platelets circulate for 10 days before losing functional capacity, and then are destroyed in the spleen.

• Hemostasis: The process of stopping bleeding. Requirements include platelets (adhesion, activation, and aggregation), clotting factors, and endothelial cells.

• Coagulation Cascade: Intrinsic and extrinsic pathways. Involved in secondary hemostasis.

• Control of Hemostatic Mechanisms: Clot retraction (fibrin strands become shorter and denser, facilitated by platelets); Lysis of blood clots (fibrinolytic system involving plasminogen, plasmin, fibrin degradation products, and D-dimers).

• Evaluation of the Hematologic System: Tests used to evaluate bone marrow function include bone marrow aspiration, bone marrow biopsy, and bone marrow iron stores measurement. Blood tests, such as a complete blood count, iron profile, serum vitamin B12, and serum folate measurements, help in the assessment.

• Alterations of Hematologic Function in Children: Includes descriptions of specific acquired and inherited disorders in erythrocytes and coagulation/platelets (ex. iron deficiency anemia, hemolytic disease of the fetus and newborn, sickle cell disease, thalassemias, and hemophilias). Detailed information about the etiology, manifestations, and further complications for each disease.

• Acquired Disorders of Erythrocytes: Includes iron deficiency anemia (most common), congenital hemolytic anemia (HDFN/erythroblastosis fetalis--alloimmune diseases). Etiology, clinical manifestations, and additional complications are noted.

• Inherited Disorders of Erythrocytes: Detailed information about hemoglobin abnormalities (e.g. Sickle cell disease, Sickle cell trait, other forms, manifestations and clinical consequences) . Alpha-thalassemia, and Beta-thalassemia (alpha and beta thalassemias, major vs minor, clinical characteristics).

• Inherited Coagulation and Platelet Disorders: Inherited disorders involving blood clotting abnormalities are highlighted (hemophilias [A, B, C]). Etiologies and symptoms are described .

• Antibody-Mediated Hemorrhagic Disease: Idiopathic thrombocytopenic purpura (ITP) characterized by platelet destruction. Etiology, manifestations (bruising and petechial rash, and complications) and prognosis are detailed.

• Leukemia: Most common childhood malignancy, including acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML). Etiology is highlighted along with clinical manifestations(pallor, fatigue, purpura, fever), blast cell involvement, and prognosis/long-term survival rate.

• Lymphoma: Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma. Inherited and acquired forms, specific cells (B-cells) involved, possible etiology, common sites of involvement (mediastinal mass), diagnostic considerations and treatments, typical prognosis, and other significant clinical features are included, are all highlighted.