Blood, Hemostasis & Blood Groups

Blood, Hemostasis & Blood Groups

Introduction

  • Blood is a fluid connective tissue that transports many substances to and from the tissues of the body.

  • Consists of:

    • Plasma

    • Extracellular matrix composed of water, proteins, ions, and other solutes.

    • Formed elements

    • Cells and cell fragments (includes RBCs, WBCs, and platelets).

  • Key components include:

    • Heart: muscular pump generating pressure to move blood through blood vessels (refer to chapter 20).

    • Blood vessels: distribute blood to body tissues (refer to chapter 21).

Functions of Blood

  • Distribution of:

    • Respiratory gases (oxygen and carbon dioxide)

    • Nutrients

    • Metabolic waste products

    • Hormones

  • Regulation of:

    • Body temperature

    • Body pH

  • Protection against infections

  • Clot formation

Characteristics of Blood

  • Classified as connective tissue due to cells surrounded by an extracellular matrix

  • Unique as the only fluid tissue of the body

  • Accounts for approximately 8% of total body weight

    • Volume: 5-6 L in men, 4-5 L in women

  • Color is influenced by oxygen saturation:

    • Dark color indicates low O2

    • Bright color indicates high O2

  • Normal blood pH ranges from 7.35 to 7.45.

Components of Blood

Plasma

  • Comprises 55% of blood volume

    • Percentage Composition by Weight:

    • Water: 91%

    • Proteins: 7%

      • Albumins: 58% (maintains colloid osmotic pressure)

      • Globulins: 38% (functional proteins such as enzymes or antibodies)

      • Fibrinogen: 4% (used in blood clotting)

    • Other Solutes: 2%

    • Key functions of plasma include acting as a solvent for other substances and transporting nutrients, electrolytes, gases, hormones, and metabolic wastes.

Formed Elements

  • Comprise 45% of blood volume:

    • Red Blood Cells (RBC)

    • White Blood Cells (WBC)

    • Platelets

  • Formed element counts per cubic mm:

    • Red Blood Cells: 4.2-6.2 million

    • White Blood Cells: 5-10 thousand

    • Type distribution:

      • Neutrophils: 60-70%

      • Lymphocytes: 20-25%

      • Monocytes: 3-8%

      • Eosinophils: 2-4%

      • Basophils: 0.5-1%

    • Platelets: 250-400 thousand

Blood Viscosity

  • Determined by the amount of RBCs

  • Hematocrit: percentage of blood volume made up of erythrocytes

    • Normal values:

    • Men: 47% (+/-5%)

    • Women: 42% (+/-5%)

  • Higher hematocrit correlates with higher viscosity.

Blood Cell Formation (Hemopoiesis/Hematopoiesis)

  • Occurs in red bone marrow

  • All formed elements originate from stem cells called hemocytoblasts.

  • The process is influenced by hormones and growth factors based on the body's needs.

Stages of Erythropoiesis

  1. Hemocytoblast transforms into proerythroblast

  2. Develops into erythroblast

  3. Further develops into reticulocyte (capable of transporting O2)

  4. Becomes erythrocyte upon release into the blood

Erythrocytes

Characteristics

  • Most numerous cells in blood: approximately 5 million per µL

  • Bi-concave disc with a diameter of about 8 µm

  • Color from hemoglobin (protein without a nucleus or mitochondria, thus cannot use O2 for ATP generation)

Main Function

  • Transport of oxygen from lungs to tissues, reliant on hemoglobin (Hb).

Structure of Hemoglobin

  • Composed of 4 chains: 2 alpha and 2 beta

    • Heme group: Contains an iron atom, can bind 4 O2 molecules, providing blood’s red color when oxygenated (oxyhemoglobin) and turning dark when deoxygenated (deoxyhemoglobin).

    • Binding properties: also binds CO2 to form carbaminohemoglobin.

Fate and Destruction of Erythrocytes

Life Span

  • 100 - 120 days

Degradation Process

  1. Macrophages engulf dying RBCs in the spleen

  2. Heme and globin are separated

    • Iron salvaged for reuse.

    • Heme degrades to bilirubin, a yellow pigment, which the liver secretes into bile and ultimately excretes in feces as stercobilin.

    • Globin metabolized into amino acids.

Roles of Hormones

  • Hypoxia stimulates kidneys and liver to secrete erythropoietin (EPO) which increases RBC production.

  • Testosterone also enhances EPO levels.

Anemia

  • Defined as an abnormally low RBC count, leading to hypoxia and decreased oxygen delivery to tissues.

Symptoms

  • Fatigue, paleness, shortness of breath, chills

Types of Anemia

  • Aplastic Anemia: Destruction or inhibition of red bone marrow.

  • Hemolytic Anemia: RBC destruction exceeds production.

  • Hemorrhagic Anemia: Blood loss causing reduction in RBC count.

  • Iron-deficiency Anemia: Lack of iron due to dietary needs or chronic blood loss.

  • Pernicious Anemia: Vitamin B12 deficiency impacting nerve and blood functionalities.

  • Sickle-Cell Anemia: Genetic mutation leading to abnormal hemoglobin (Hemoglobin S), which causes RBCs to have a sickle shape, obstructing small vessels and causing tissue hypoxia.

Leukocytes

Overview

  • WBCs constitute <1% of blood volume and play critical roles in immune response.

  • Ability to leave capillaries via diapedesis and move through tissues by positive chemotaxis.

  • Normal WBC count: 5,000 to 10,800 cells/mm³

    • Leukocytosis: Abnormally high WBC count, often indicative of infection or inflammation.

Leukopoiesis

  • Formation of WBCs from hemocytoblasts in the bone marrow.

  • Stimulated by chemical messengers such as interleukins (ILs) and colony-stimulating factors (CSFs).

Classification of Leukocytes

  1. Granulocytes: Neutrophils, Eosinophils, Basophils

    • Large cells with distinct staining granules that perform phagocytosis.

    • Neutrophils: Most numerous, multi-lobed nuclei, function as primary bacterial defenders.

    • Eosinophils: Target larger parasites and modulate immune responses.

    • Basophils: Rare, release histamine during inflammatory responses.

  2. Agranulocytes: Lymphocytes (B and T cells crucial for immunity) and Monocytes (transform into macrophages effective against viruses and bacteria).

Disorders of Leukocytes

  • Leukopenia: Low WBC count, often due to drug therapies.

  • Leukemia: Uncontrolled production of leukocytes, often resulting in many immature, non-functional WBCs circulating in the blood.

    • Two types: Myelocytic and Lymphocytic leukemias.

Platelets

  • Also known as thrombocytes

  • Contain bioactive substances (serotonin, Ca²⁺, ADP, PDGF) important for hemostasis

  • Regulated by thrombopoietin

Hemostasis

Overview and Stages

  1. Vascular Spasm: Immediate vasoconstriction of damaged blood vessels to reduce bleeding. Influencing factors include injury, local tissue and platelets, and pain reflexes.

  2. Formation of Platelet Plug: Platelets adhere to exposed collagen, swell, and release granule contents (ADP, thromboxane A2, serotonin) enhancing adhesion and vascular spasm.

  3. Coagulation (Clotting): Involves multiple factors leading to insoluble fibrin formation and a gel-like clot.

    • Extrinsic Pathway: Triggered by tissue factor (TF) from vessel damage, faster pathway.

    • Intrinsic Pathway: Activated by platelets and their factors.

    • Both pathways converge to activate factor X, which forms prothrombinase, crucial for conversion of prothrombin to thrombin.

Final Steps in Clot Formation

  • Thrombin converts fibrinogen into insoluble fibrin, a mesh that traps RBCs and platelets to form a clot.

  • Clot retraction occurs within 30-60 minutes due to actin and myosin shortening the fibrin strands.

Fibrinolysis

  • The enzymatic breakdown of the clot is initiated by converting plasminogen to plasmin. Plasmin digests fibrin to dissolve the clot.

Disorders of Hemostasis

  • Thromboembolic Disorders: Involves clotting in normal vessels (thrombus) or obstruction via an embolus, leading to conditions like strokes.

  • Hemophilia: Lack of clotting factors, increasing bleeding risk.

  • Other conditions like hepatitis or liver diseases can decrease clotting factor production.

Medications Affecting Hemostasis

  • Aspirin: Inhibits thromboxane production.

  • Coumadin/Warfarin: Blocks Vitamin K utilization.

  • TPA: Initiates clot dissolution to enhance blood flow.

Blood Groups

ABO System

  • Based on antigens present on RBC membranes, leading to classifications:

    • Type A: Has A antigens; plasma contains anti-B antibodies.

    • Type B: Has B antigens; plasma contains anti-A antibodies.

    • Type AB: Has both A and B antigens; no anti-A or anti-B antibodies in plasma.

    • Type O: Lacks A and B antigens; plasma contains both anti-A and anti-B antibodies.

Rh Factor

  • Includes antigens (C, D, E) with D antigen being clinically significant.

  • Antibodies to Rh antigens form after exposure during birth or with transfusions, leading to potential reactions in subsequent exposures.

Hemolytic Disease of the Newborn (Erythroblastosis Fetalis)

  • Rh antibodies can cross the placenta, potentially attacking the fetus's RBCs.

  • RhoGAM serum can be provided to mothers to prevent sensitization of fetal RBCs.

Transfusion Reactions

  • Occur when transfused blood does not match the recipient's antigens, leading to agglutination and potential clots causing vital organ damage.