Hematologic System: A Review

Hematologic System: A Review

Introduction

  • Presenter: C. Constantin, PhD, RNC

  • Source slides adapted from Huether and McCance

Topics Covered

  • Blood Composition

  • Hematopoiesis

    • Erythropoiesis

    • Hemoglobin

    • Leukocytes

    • Platelets

  • Hemostasis

    • Clotting Cascade

    • Fibrinolysis

    • Sources: Porth (2015)

Blood Composition

Components of Blood

  • Plasma: Liquid part of blood containing proteins and inorganic materials.

  • Buffy Coat: Composed of platelets and leukocytes (white blood cells).

  • Formed Elements: Primarily erythrocytes (red blood cells).

Blood Volume

  • Average total blood volume in adults: 5-6 Liters (approximately 6 quarts).

Whole Blood Composition Breakdown (by volume)

  • Plasma: Averages 50-55% of blood volume.

    • Plasma Protein Composition:

    • Proteins: 7% of plasma weight

      • Albumins: 57% of total plasma protein

      • Globulins: 38% (functions include being enzymes and antibodies)

      • Fibrinogen: 4% (essential for blood clotting)

      • Prothrombin: 1% (precursor to thrombin)

    • Water: 91% of plasma

    • Other Solutes: Includes ions, nutrients, waste products, gases, regulatory substances (2% of plasma).

Formed Elements (mainly erythrocytes)

  • Total formed elements: 45% of blood volume.

    • Leukocytes Count: Less than 1%

    • Neutrophils: 60%-70%

    • Lymphocytes: 20%-25%

    • Monocytes: 3%-8%

    • Eosinophils: 2%-4%

    • Basophils: 0.5%-1%

  • Data Source: Patton KT, Thibodeau GA: Structure & function of the body, 15th ed. St Louis, 2016, Mosby.

Plasma and Plasma Proteins

  • Plasma: Aqueous liquid containing both organic and inorganic elements.

    • Plasma proteins made in the liver play crucial roles in various bodily functions, including maintaining osmotic pressure, transporting nutrients, and supporting the immune system.

  • Role of Plasma Proteins: Vital for various functions in the bloodstream.

    • Albumin: Constitutes 60% of total plasma proteins. (most common abundant protein in plasmaIt helps maintain colloidal osmotic pressure, contributes to the transport of hormones, fatty acids, and drugs, and serves as a reservoir for amino acids. )

      • If albumin is low colloid osmotic fails leads to EDEMA, which results in fluid accumulation in tissues and can impact organ function. Low albumin levels can also contribute to changes in drug pharmacokinetics, affecting the efficacy and distribution of medications in the body. This underscores the importance of monitoring albumin levels in patients, particularly those with liver disease, malnutrition, or chronic inflammatory conditions. In addition to albumin, globulins play a significant role in immune function and transportation of other molecules, making up approximately 35% of total plasma proteins. Furthermore, fibrinogen is crucial for blood coagulation, and its absence can lead to increased bleeding risk. It is essential to evaluate not only these proteins but also other hematological parameters to obtain a comprehensive understanding of a patient's overall health status.

    • Globulins: Serve as enzymes, antibodies, and transport carriers.

    • Other proteins include fibrinogen, prothrombin, and antibodies.

Hematopoiesis (Blood Cell Production)

Overview

  • Constant production occurring primarily in the bone marrow after birth.

    • Hematopoiesis is the process of making RBC in bone marrow, which includes several stages such as differentiation of stem cells into erythrocytes, leukocytes, and thrombocytes. This intricate process is regulated by various growth factors and hormones, ensuring a balanced supply of each cell type to maintain homeostasis within the bloodstream.

      • In the fetuses, production also occurs in

      • liver and spleen.

  • Extramedullary Hematopoiesis: Blood cell production occurring in tissues other than bone marrow, usually indicative of disease (primarily liver and spleen).

Bone Marrow Function

  • Types of Bone Marrow:

    • Red Bone Marrow: Produces red blood cells (RBC).

    • Yellow Bone Marrow: Does not produce RBC.

      • yellow is mainly fat but can turn into Redbone marrow under certain conditions, such as increased demand for blood cell production.

      • Functions in various capacities such as storing fat and supporting the immune system.

      • Hematopoiesis: The process of blood cell production that primarily occurs in the red bone marrow, where stem cells differentiate into various blood cells including RBCs, platelets, and white blood cells. In contrast, red bone marrow is crucial for maintaining the body's blood cell supply and can be stimulated to produce more cells during instances of significant blood loss or increased physical demand.

  • Active Bone Marrow Locations in Adults:

    • Pelvic bones

    • Vertebrae

    • Cranium and mandible

    • Sternum and ribs

    • Humerus

    • Femur

Erythropoiesis (Formation of Red Blood Cells)

  • Process occurs in the bone marrow, stimulated by erythropoietin released by the kidney in response to low oxygen (O2) tension.

  • Factors influencing erythropoiesis: Granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and insulin-like growth factor-1 (IGF-1).

Reticulocytes

  • Immature RBCs, normally making up about 1% of RBCs.

  • Increased levels indicate enhanced RBC production.

  • Average lifespan of RBCs: Approximately 120 days.

    • Destruction typically occurs in the liver and spleen.

Required Nutrients for Production

  • Nutritional Requirements include:

    • Iron

    • Vitamin B12

    • Folate (vitamin B9): Essential for DNA and RNA synthesis, repair, and RBC production; stored in the liver.

  • Lack of intrinsic factor leads to impaired absorption of vitamin B12, increasing risk for pernicious anemia. Folate deficiency is more common and supplements are often prescribed for pregnant women to prevent neural tube defects.

Regulation of Erythropoiesis

  • The circulation of red blood cells remains constant under normal conditions.

  • Erythropoietin Production: Manufactures in the peritubular cells of the kidney, stimulated by hypoxia (low oxygen levels), leading to increased release of erythropoietin.

Mechanism Illustration of Erythropoiesis Regulation

  • Decreased RBCs lead to:

    • Reduced hemoglobin synthesis

    • Decreased blood flow

    • Hemorrhage

    • Increased oxygen consumption by tissues

    • Decreased arterial oxygen levels (indicating tissue hypoxia) stimulate erythropoietin release from the kidney.

Hemoglobin

Structure and Function

  • Hemoglobin: Main component carrying oxygen in mature red blood cells.

  • Composition: Two pairs of polypeptide chains (globins) attached to a heme molecule containing iron.

    • Variants of globin include: alpha, beta, gamma, delta, epsilon, or zeta chains.

Properties of Hemoglobin

  • Oxyhemoglobin: Fully saturated hemoglobin carrying four oxygen molecules.

  • Typical adult hemoglobin consists of:

    • Two alpha chains

    • Two beta chains

    • Four heme complexes (each contains iron and protoporphyrin).

Normal Destruction of Erythrocytes

  • Aged red blood cells are sequestered and destroyed by macrophages primarily in the spleen.

    • If spleen is absent, the liver takes over.

  • Bilirubin Production: Following destruction, porphyrin is reduced to bilirubin and transported to the liver where it is secreted in the bile.

    • Bilirubin: Insoluble in water; must be conjugated by the liver to a water-soluble form.

    • If liver has problems you wont be able to process Bilirubin

Hyperbilirubinemia After the destruction of aged red blood cells, porphyrin is reduced to bilirubin. This initial form is **unconjugated bilirubin**, which is insoluble in water and is transported to the liver. In the liver, this unconjugated bilirubin undergoes a process called conjugation, where it is converted into **conjugated bilirubin**. Conjugated bilirubin is water-soluble and is then secreted in the bile. If the liver has problems, it may not be able to process (conjugate) bilirubin effectively, leading to an accumulation of unconjugated bilirubin.

  • Increased breakdown of RBCs can lead to hyperbilirubinemia, which manifests as jaundice.

Leukocytes (White Blood Cells)

  • Leukocyte count increases in response to:

    • Infection

    • Steroids

    • Depleted reserves in the marrow.

Types of Leukocytes

  • Hematopoietic Stem Cells give rise to:

    • Common lymphoid progenitors:

    • B lymphocytes

    • T lymphocytes

    • NK cells

    • Common myeloid progenitors:

    • Neutrophils

    • Monocytes

    • Basophils

    • Eosinophils

    • Megakaryocytes (produce platelets).

Platelets (Thrombocytes)

  • Derived from stem cells and progenitor cells differentiating into megakaryocytes.

  • Platelet characteristics:

    • Lack nucleus

    • Lifespan: About 10 days; destroyed in the spleen.

    • 2/3 of platelets are in circulation; 1/3 reside in the spleen.

  • Thrombopoietin (TPO): Main regulator of platelet numbers, produced in the liver.

Hemostasis (Arrest of Bleeding)

Phases of Hemostasis

  1. Vasoconstriction: Immediate constriction at site of injury (vasospasm).

  2. Formation of Platelet Plug: Platelets adhere to the injury site and recruit others, forming a plug.

  3. Activation of the Clotting Cascade: Complex biochemical processes that lead to the formation of a blood clot.

  4. Formation of a Blood Clot: Fibrin reinforces the platelet plug, converting it into a stable clot.

  5. Clot Retraction and Dissolution: Post-hemostatic process involves the retraction of the clot and dissolution through fibrinolysis.

Clotting Cascade Details

  • Intrinsic Pathway: Activated by blood vessel or blood injury.

  • Extrinsic Pathway: Initiated by tissue factor (faster response).

  • Key components include thromboplastin, prothrombin, thrombin, fibrinogen, and various coagulation factors (e.g., Factors VIII, IX, X).

Regulation of Clot Formation

  • Natural anticoagulants (e.g., Antithrombin III, Proteins C and S) prevent excessive clot size growth.

  • Fibrinolytic System: Dissolves clot post-formation via plasmin, allowing blood flow restoration and tissue repair.

Fibrinolysis Process

  • Process Illustration: Tissue-type plasminogen activator (t-PA) converts plasminogen to plasmin, which breaks down fibrin into fibrin degradation products.

Anticoagulants

  • Warfarin: Common anticoagulant that decreases prothrombin and other pro-coagulants; interferes with vitamin K metabolism.

    • Patients on Warfarin must monitor dietary vitamin K.

    • Patients should not eat lots of leafy greens or take vitamin K supplements, as these can counteract the effects of Warfarin and increase the risk of clotting.

  • Heparin: Naturally occurring substance, released by mast cells; binds to antithrombin III enhancing its effect to inactivate thrombin and factors Xa.

    • Heparin prevents clotting

Laboratory Tests

  • Prothrombin Time (PT): Assesses function of the extrinsic pathway of coagulation.

  • Partial Thromboplastin Time (PTT): Evaluates intrinsic pathway's function of coagulation.