BMS PPT 2

Basic Medical Science I

• This course covers the epidemiology, pathogenesis, and pathophysiology of diseases related to hematopoietic and lymphatic tissue.
• It also classifies different types of hematopoietic disorders and explains the maturation sequence and function of various immune cells (granulocytes, mast cells).
• Understanding the effects of over-production and underproduction of leukocytes is a key component.
• The activation sequence and function of thrombocytes are discussed.

Formed Elements of Blood

• Red blood cells (RBCs), also known as erythrocytes, are responsible for transporting oxygen.
• White blood cells (WBCs) or leukocytes are part of the immune system.
• Platelets, or thrombocytes, are cell fragments involved in blood clotting.

Erythrocytes (Red Blood Cells)

• Erythrocytes make up 99.9% of blood's formed elements.
• RBC production requires amino acids, iron, and vitamins B6, B12, and folic acid.
• RBCs are small, highly specialized discs (~8μm) that lack nuclei, mitochondria, and ribosomes.
• Adults have a lifespan of ~120 days, and newborns ~80 days.
• Their shape and size are crucial for absorbing and releasing oxygen and carbon dioxide efficiently and allowing smooth flow through blood vessels.

Hemoglobin (Hb)

• Hemoglobin is a protein that transports respiratory gases.
• It’s a complex, quaternary structure containing iron (heme) that enables RBCs to carry significantly more oxygen than plasma alone.
• Normal hemoglobin levels are ~14–18g/dl in adult males.

Hemoglobin Structure and Formation

• Hemoglobin has four subunits (alpha & beta chains) with heme groups.
• Hemoglobin A (adult hemoglobin) has two alpha and two beta chains.
• Problem: Sickle cell anemia occurs when hemoglobin A's oxygen binding is less effective, leading to mutated hemoglobin.
• Fetal hemoglobin (HbF) has gamma subunits; it binds oxygen more strongly.

Measuring RBCs

• Red blood cell count (RBCs) per microliter of whole blood
• Hemoglobin (g/dL): measures the hemoglobin content in blood.
• Hematocrit (Ht or HCT): percentage of RBCs in centrifuged whole blood, also known as packed cell volume (PCV).
• Mean corpuscular volume (MCV): average RBC volume.

Hemoglobin Structure

• Hemoglobin contains four heme groups, each with an iron atom.
• Oxygen binds to the iron in heme groups.
• Deoxyhemoglobin is the form without bound oxygen (purple-blue).
• Oxyhemoglobin is the form with bound oxygen (bright red).
• Carbon dioxide binds to the globin part for transport to the lungs.

Hematopoiesis

• Hematopoiesis is the process of producing formed elements.
• It occurs in the myeloid and lymphoid stem cells.
• Various nutrients, including amino acids, iron, vitamin B12, vitamin B6, and vitamin B9, are required for healthy hematopoiesis.

Erythropoietin (EPO)

• EPO is a hormone released by the kidneys in response to low blood oxygen levels, not to the quantity of red blood cells.

• It stimulates RBC formation in the bone marrow.

• Low renal oxygenation triggers the release of the hypoxia-inducible factor (HIF-1), stimulating EPO production.

RBC Disorders

• Polycythemia is an excess of RBCs, often associated with underlying conditions.
• Anemia is a deficiency of RBCs. Types include hypo-proliferative, hemolytic, and bleeding anemias. Anemia is often caused by decreased RBC production, increased RBC destruction, or blood loss.

Neutrophils

• Neutrophils are the most common type of white blood cell and play a crucial role in the body's defense against bacterial infections.

• They are very active, first at site of injury or infection and form pus.

• They are phagocytic cells, engulfing and digesting microbes through lysosome enzymes that have bactericidal action.

Eosinophils

• Eosinophils are involved in immune responses and have activity against parasitic infections.

• They have weak phagocytic activity but are active against parasites.

• Their granules contain enzymes, reactive oxygen forms, and major basic protein that kill parasites.

They participate in allergic reactions by decreasing inflammation from inflammatory cells due to their histaminase function.

Basophils

• Basophils are the least common type of white blood cell.

• They release histamine and heparin, which have roles in vasodilation and anticoagulation, respectively.

• Functionally similar to mast cells, causing inflammation and allergic reactions by degranulation that occurs when IgE antibodies bind to the allergen antigens on the basophil surface.

Monocytes

• Monocytes are large, spherical white blood cells with indented or C-shaped nuclei.

• They mature into macrophages in peripheral tissues, participating in phagocytosis, and antigen presentation.

• Macrophages play an important role in immune functions.

Lymphocytes

• Lymphocytes originate from lymphoid stem cells in the bone marrow and differentiate into various subtypes.

• B cells, located in bone marrow, develop into plasma cells (activated B cells) that secrete antibodies for humoral immunity.

• T cells, which develop in the thymus, and Natural Killer (NK) cells play major roles in cell-mediated immunity and destroying abnormal cells, respectively.

• Most lymphomas are of B-cell origin.

Malignancies

• Leukemia involves uncontrolled proliferation of blood cells in the bone marrow.
• Lymphoma involves solid tumors in lymphoid tissues.

Acute Myeloid Leukemia (AML)

• Characterized by the uncontrolled development of precursor myeloblast cells.
• This heterogeneous group of precursor myeloblast cells interferes with maturation.
• Common risk factors for AML include prior exposure to radiation, chemotherapy, or chemicals as well as pre-existing blood disorders such as myelodysplastic syndromes.

Chronic Myelogenous Leukemia (CML)

• Characterized by the abnormal reproduction of granulocytes and other blood cells.
• A specific translocation occurs between chromosomes (9 & 22) that causes this and interferes with cell maturation.

Acute Lymphoblastic Leukemia (ALL)

• ALL originates from the malignant proliferation and replacement of normal bone marrow cells.

• This uncontrolled proliferation often occurs in lymphoblasts resulting from various abnormalities.

• A variety of types of ALLs exist, depending on whether B-cells or T-cells divide and proliferate abnormally.

Chronic Lymphocytic Leukemia(CLL)

• CLL involves the abnormal proliferation of B lymphocytes that mature in lymphoid organs.

• This often leads to a decreased antibody response and immunodeficiency.

• Approximately 80% of patients with CLL have abnormal B lymphocytes that possess the CD19+ and CD23+ surface markers.

• Some cases demonstrate CD5 expression, characteristic of T-cell receptors, highlighting unique features.

Hodgkin's Lymphoma

• Hodgkin's Lymphoma (HL) is a type of lymphoma arising from the germinal centers of B lymphocytes.

• It's characterized by the presence of Reed-Sternberg cells, which show the disruption of transcription processes.

• Loss of apoptosis and increased cytokine production lead to unfavorable conditions within the body, and the development of this disease.

Non-Hodgkin's Lymphoma (NHL)

• NHL is a type of lymphoma with diverse characteristics and origins.

• This heterogenous cell disorder is frequently derived from B cell progenitors, matured B cells, and T cells, as well as Natural Killer (NK) cells.

• It's characterized by the uncontrolled transformation of these lymphoma cells.

• This is often due to abnormalities like p53, c-myc, and bcl-6, interfering with apoptosis or proliferation, resulting in numerous uncontrolled divisions.

• Different forms of NHL arise from these cells, including aggressive forms like Diffuse Large B-cell Lymphoma and more indolent forms like Follicular Lymphoma.