MS

Blood, Lymph and Lymph Nodes Part 1

Lecture Overview

  • Focus of Lecture: Blood, Lymph, and Lymph Nodes (Chapter 12). This lecture provides a comprehensive understanding of the circulatory and lymphatic systems, their components, functions, and associated pathologies.

  • Introduction: Setting the stage for discussion about blood and its components, emphasizing their vital roles in maintaining homeostasis.

  • Instructor mentions a dove named 'Pidge' joining the discussion, a lighthearted way to engage students.

Blood Overview

  • Definition of Blood: A specialized fluid connective tissue that circulates throughout the entire body, delivering essential substances and removing waste products. It is a complex mixture of cells, cell fragments, and plasma.

  • Plasma: The clear, yellowish liquid extracellular matrix in which cellular components (red blood cells, white blood cells, and platelets) are suspended. It constitutes about 55\% of blood volume and is composed of:

    • Plasma Proteins: Primarily synthesized in the liver, these include albumin (maintains osmotic pressure, transports substances), globulins (antibodies, transport proteins), and fibrinogen (essential for blood clotting).

    • Serum: Blood plasma from which the fibrinogen and other clotting proteins have been removed. It is essentially plasma without the capacity to clot.

Functions of Blood

  • Transportation:

    • Carries oxygen from the lungs to all body cells via hemoglobin.

    • Transports nutrients (e.g., glucose, amino acids, vitamins, minerals) absorbed from the digestive tract to various tissues.

    • Carries metabolic waste products (e.g., urea, creatinine, lactic acid, carbon dioxide) to the kidneys, lungs, and liver for excretion.

    • Distributes hormones from endocrine glands to target organs.

  • Regulation:

    • Maintains body temperature by absorbing and distributing heat throughout the body and to the skin surface for dissipation.

    • Regulates blood pH through buffer systems (e.g., bicarbonate buffer system) to keep it within a narrow range (approximately 7.35-7.45).

    • Aids in tissue fluid content regulation by exchanging water between the plasma and interstitial fluid, influenced by plasma proteins that maintain osmotic pressure.

  • Defense:

    • Contains white blood cells (leukocytes) that protect against pathogens (bacteria, viruses, fungi, parasites) and initiate immune responses.

    • Contains platelets and clotting factors that prevent blood loss through hemostasis (blood clotting).

Cellular Components of Blood

  • Erythrocytes (Red Blood Cells):

    • Definition: Biconcave disc-shaped cells highly specialized for transporting oxygen from the lungs to body tissues and a smaller amount of carbon dioxide back to the lungs.

  • Leukocytes (White Blood Cells):

    • Different types including neutrophils, eosinophils, basophils (granulated leukocytes), lymphocytes, and monocytes (agranulated leukocytes), each with specific roles in immunity.

    • Note: Mammal leukocytes are nucleated, but mature erythrocytes are not. Birds and reptiles have nucleated erythrocytes and heterophils, which are functionally equivalent to neutrophils but structurally different.

  • Thrombocytes (Platelets): Small, anucleated cell fragments crucial for initiating blood clotting and maintaining vascular integrity.

Hematopoiesis

  • Definition: The continuous, regulated process of blood cell production, differentiation, and maturation, occurring primarily in the red bone marrow of adults. This ensures a constant supply of new blood cells to replace aging or damaged ones.

  • Liver and spleen also contribute to hematopoiesis during certain conditions, such as severe anemia or fetal development.

  • Origin: All blood cells (erythrocytes, leukocytes, and thrombocytes) derive from a common ancestor—pluripotential hematopoietic stem cells (HSCs)—located in the red bone marrow. These stem cells have the capacity to self-renew and differentiate into all types of blood cells.

  • In fetuses, hematopoiesis occurs primarily in the liver and spleen; in newborns and young animals, it predominantly shifts to the red bone marrow of long bones and flat bones.

Red Bone Marrow

  • Importance:

    • There is a high demand for blood cells as animals grow (mass increases over 200\%), requiring continuous and robust blood cell production.

    • Core biopsy samples (e.g., from the iliac crest) may be taken for disease screening, allowing examination of cellularity, maturation patterns, and presence of abnormal cells.

    • Clinical relevance: Essential in diagnosing and understanding conditions such as non-regenerative anemias (where the marrow fails to produce enough red blood cells) and various neoplastic conditions (cancers, e.g., leukemias, affecting blood cell production).

Erythropoiesis

  • Definition: The specific process of creating red blood cells from hematopoietic stem cells.

  • Location: Primarily occurs in the red bone marrow, but the process is highly regulated by the kidneys via interstitial cells.

  • Triggered by the hormone erythropoietin (EPO), which is released by the kidneys in response to hypoxia (insufficient oxygen delivery to tissues). EPO stimulates the bone marrow to increase erythrocyte production.

  • Lifecycle of Red Blood Cells:

    • Stages: The process begins with rubroblasts, progressing through prorubrocytes, rubrocytes, and metarubricytes. These stages involve cell division and hemoglobin synthesis.

    • Once red blood cells reach the rubricyte stage, further mitosis (cell division) is halted.

    • The cells then mature into polychromatophils (also known as reticulocytes in some contexts, or immature red blood cells that still contain remnants of RNA), and finally mature reticulocytes, which are released into the bloodstream and still have residual RNA but no nucleus. They mature into erythrocytes within 1-2 days in circulation.

Thrombopoiesis

  • Definition: The formation of thrombocytes (platelets) from extremely large cells called megakaryocytes in the bone marrow.

  • Megakaryocyte: A large, polyploid (multiple sets of chromosomes) bone marrow cell that undergoes cytoplasmic fragmentation, releasing thousands of discrete, anucleated cytoplasmic fragments into the circulation, which are platelets.

Leukopoiesis

  • Definition: The formation and differentiation of white blood cells via three specific pathways, all originating from hematopoietic stem cells in the bone marrow:

    • Granulopoiesis: Creation and maturation of granulated leukocytes, including neutrophils (phagocytosis of bacteria), basophils (allergic reactions, inflammation), and eosinophils (parasitic infections, allergic reactions).

    • Lymphopoiesis: Production of lymphocytes (T cells, B cells, NK cells), which are central to adaptive immunity.

    • Monopoiesis: Forming monocytes, which circulate in the blood before migrating into tissues to become macrophages, key phagocytic cells.

Characteristics of Blood Components

Erythrocytes

  • Plentiful (most numerous blood cells), highly specialized due to their biconcave shape and lack of organelles, non-nucleated in mammals (which maximizes space for hemoglobin).

  • Function: Primarily to transport oxygen and a lesser amount of carbon dioxide. They utilize plasma glucose for energy through anaerobic glycolysis as they lack mitochondria.

  • Shape: Biconcave disc (thinner in the middle), which provides a large surface-to-volume ratio for efficient gas exchange and enables them to fold and deform easily to pass through narrow capillaries for optimal oxygen transport and light passage for diagnostic examination.

Hemoglobin

  • Composition: A complex protein composed of four heme units (each containing an iron ion that reversibly binds oxygen) and a globin unit (a protein composed of four polypeptide chains, which binds carbon dioxide).

  • Function: The primary molecule responsible for transporting oxygen (forming oxyhemoglobin, which gives arterial blood its bright red color) and carbon dioxide (forming carbaminohemoglobin or deoxyhemoglobin, which gives venous blood its darker red/purplish hue).

Red Blood Cell Lifespan

  • Destruction occurs through two main mechanisms:

    • Intravascularly (approximately 10\%): Cells lyse within blood vessels, releasing hemoglobin directly into the plasma. This free hemoglobin binds to haptoglobin and is transported to the liver for processing to prevent kidney damage.

    • Extravascularly (approximately 90\%): Older or damaged red blood cells are removed from circulation by macrophages, primarily in the spleen, liver, and bone marrow. This is the main route of destruction.

  • Aging cells: As red blood cells age (lifespan varies by species, e.g., dogs ~110-120 days, cats ~65-76 days), enzyme activity decreases, and their cell membranes lose deformability and become more fragile, marking them for removal.

Hemolysis

  • Intravascular Hemolysis: Occurs within blood vessels; hemoglobin is released directly into the bloodstream. If haptoglobin is saturated, free hemoglobin can be filtered by the kidneys, leading to hemoglobinuria (dark red or brown urine).

  • Extravascular Hemolysis: Involves macrophage activity, primarily in the spleen. Macrophages engulf and digest aged red blood cells, processing hemoglobin into biliverdin, which is then converted to unconjugated bilirubin. This unconjugated bilirubin is transported to the liver, where it is conjugated and excreted in bile.

Jaundice and Hemoglobinuria

  • Conditions such as jaundice (icterus) arise from an excessive accumulation of bilirubin in the blood, leading to yellowing of tissues (skin, sclera, mucous membranes). This can result from:

    • Pre-hepatic (hemolytic) jaundice: Excessive hemolysis overwhelms the liver's ability to process bilirubin.

    • Hepatic jaundice: Liver dysfunction impairs bilirubin conjugation and excretion.

    • Post-hepatic (obstructive) jaundice: Obstruction of bile flow prevents bilirubin excretion.

  • Hemoglobinuria refers to the presence of free hemoglobin in the urine, typically resulting from severe intravascular hemolysis, leading to dark red or brown urine.

Platelets

  • Definition: Not complete cells, but essentially anucleated cytoplasmic fragments derived from megakaryocytes in the bone marrow. They are roughly 2-4\ \mu m\ in diameter.

  • Lifespan: Approximately five to seven days in circulation before being removed by macrophages.

  • Function in hemostasis: Key roles in maintaining vascular integrity, initiating clot formation (primary hemostasis), and contributing to the coagulation cascade (secondary hemostasis) to prevent excessive bleeding from damaged blood vessels.

Platelet Activation and Aggregation

  • When a vessel wall is damaged, circulating platelets rapidly adhere to exposed subendothelium (especially collagen fibers) via specific receptors, undergoing activation.

  • This activation leads to a change in platelet shape (from disc-like to spiky) and the release of granules containing pro-coagulant factors (e.g., ADP, serotonin, thromboxane A_2$$).

  • Released factors promote further platelet aggregation, forming a primary hemostatic plug at the site of injury. Simultaneously, the exposed tissue factors activate the coagulation cascade, leading to thrombin production.

  • Thrombin facilitates further platelet shape changes and aggregation and converts fibrinogen to fibrin, which stabilizes the platelet plug, forming a more robust secondary hemostatic plug (clot).

  • Clinical implications of platelet deficiencies (thrombocytopenia) or dysfunctional platelets (thrombopathia) include:

    • Petechiae (small, pinpoint hemorrhages on skin and mucous membranes).

    • Ecchymoses (larger bruise-like hemorrhages).

    • Prolonged bleeding from minor injuries or surgical sites, and potential life-threatening bleeding disorders.

Clinical Case Example

  • A case study illustrating the importance of platelets in preventing excessive bleeding following venipuncture in a dog with severe periodontal disease. This dog presented with unusually prolonged bleeding after a routine blood draw, indicating a primary hemostasis issue. Diagnostic testing revealed significantly low platelet counts (thrombocytopenia), which was likely exacerbated by the underlying chronic inflammation and potential immune-mediated processes or bone marrow suppression related to the periodontal disease, highlighting how systemic health can impact hemostasis.