Blood, Blood Components and Blood Functions

Blood, Blood Components, and Blood Functions

Learning Objectives

• State the type of tissue blood is.

• Name the formed elements found in blood.

• Name the liquid portion of the blood.

• State the percentage range of whole blood that is formed elements.

• State the percentage range of whole blood that is plasma.

• Identify the blood test used to fractionate whole blood and measure the percentage of formed elements.

• State which formed element is the most abundant.

• List the functions of blood.

• Define hydrostatic pressure, concentration gradient, and osmosis.

• Describe blood regarding temperature, pH, viscosity, and volume.

Blood and Its Components

A Fluid Connective Tissue

• Blood is classified as a fluid connective tissue comprising a matrix called plasma and formed elements (cells and cell fragments).

• Whole blood refers to the combination of plasma and formed elements.

• The average volume of whole blood in an adult male is 5-6 liters (5.3-6.4 quarts) while in an adult female it is 4-5 liters (4.2-5.3 quarts). The differences in blood volume between sexes primarily reflect differences in average body size.

Plasma

• Plasma constitutes 46-63% of the volume of whole blood.

• The composition of plasma is comparable to that of interstitial fluid due to continuous exchange of water, ions, and small solutes across capillary walls.

  • Primary differences between plasma and interstitial fluid:

  1. Levels of respiratory gases (oxygen and carbon dioxide).

  2. Concentration and types of dissolved proteins (plasma proteins cannot cross capillary walls).

Formed Elements

• Formed elements account for 37-54% of the volume of whole blood, consisting of:

  • Platelets (less than 1%)

  • White blood cells (WBC) (about 1%)

  • Red blood cells (RBC) (99.9% of formed elements).

• Hematocrit (he-MAT-ō-krit) is the percentage of formed elements in a sample of blood, measured to assess blood composition. The normal hematocrit values are:

  • Adult males: 46%

  • Adult females: 42%

• Differences in hematocrit primarily stem from hormonal influences:

  • Androgens (male hormones) stimulate red blood cell production.

  • Estrogens (female hormones) do not significantly influence red blood cell production.

• Hemopoiesis (he-mō-poy-Ē-sis), or hematopoiesis, is the process of formed element production, occurring from two populations of stem cells:

  1. Myeloid stem cells

  2. Lymphoid stem cells

Functions of Blood

• Blood performs several critical functions:

  • Transportation of:

  • Nutrients

  • Gases (oxygen, carbon dioxide)

  • Wastes

  • Hormones

  • Stem cells

  • Regulation:

  • Fluid balance

  • pH levels

  • Temperature control

  • Defense/Protection:

  • Inflammation response

  • Limiting spread of infection

  • Destruction of microorganisms and cancer cells

  • Initiation of clotting processes

  • Neutralization of toxins.

Physical Characteristics of Blood

Composition

• Whole blood consists of:

  • Plasma: The fluid portion, composed mainly of water, dissolved proteins, and other solutes.

  • Formed elements: Cells, cell fragments, and solids. Different factors affect the movement of substances between blood and tissues, including:

  • Hydrostatic pressure

  • Concentration gradients

  • Osmosis

• The hematocrit confirms the percentage of formed elements in blood, usually between 37-54%. The "buffy coat" visible in fractionated blood contains WBCs and platelets, accounting for less than 1% of the sample.

Blood Characteristics

• Temperature: Approximately 38°C (100.4°F), slightly higher than normal body temperature.

• Viscosity: About 5 times that of water, resulting from solute content within blood causing thick, sticky consistency.

• pH: Slightly alkaline, falling within the range of 7.35 to 7.45.

• Blood volume: Comprises about 7% of total body weight:

  • Adult male: 5-6 liters

  • Adult female: 4-5 liters

  • Calculate blood volume by multiplying body weight in kg by 7%.

Further Learning Objectives

• Recall the percentage of whole blood that is plasma.

• Identify the most abundant plasma protein and its approximate percentage.

• List classes of plasma proteins and their functions.

• Explain plasma's role in transporting substances throughout the body.

• Course of production for plasma proteins.

• Identify formed elements with their common names and two designations for each.

• Define osmolarity, hematopoiesis, and fractionation.

• Identify the blood test used for measuring the formed elements percentage in a blood sample.

Plasma Overview

Composition

• Plasma constitutes 46 to 63% of blood volume and consists of more than 90% water.

• Extracellular Fluid (ECF) includes interstitial fluid (IF) and plasma, with equal exchange of water, ions, and solutes across capillaries.

• More fluid is delivered to tissues than removed, with the remainder collected via the lymphatic system.

Plasma Proteins

• Plasma proteins are too large to cross capillary gaps, includes:

  • Albumins (60%): Major contributors to plasma osmolarity and blood viscosity, transport fatty acids, hormones, and buffer blood pH.

  • Globulins (35%):

  • Gamma Globulins: Antibodies (immunoglobulins).

  • Transport globulins: Hormone-binding proteins, metalloproteins, apolipoproteins/lipoproteins, and steroid-binding proteins.

  • Fibrinogen (4%): Soluble protein essential for clotting, converted to insoluble fibrin.

  • Other proteins: Including enzymes and hormones (1%).

Functions of Plasma

• Plasma contains substances essential for various bodily functions:

  • Nitrogenous wastes and free amino acids.

  • Nutrient transport: Includes glucose, fatty acids, cholesterol, phospholipids, vitamins, and minerals from digestive tract to cells.

  • Gas transport: Oxygen, carbon dioxide, and nitrogen are carried by plasma.

  • Electrolytes: Primarily sodium ions (Na+), which constitute about 90% of positively charged ions (cations) in plasma, affecting blood osmolarity, blood volume, and blood pressure.

Sources of Plasma Proteins

• >90% produced in the liver; liver disease can lead to significant decreases in these proteins, causing bleeding and clotting issues.

• Gamma globulins: Produced by plasma cells derived from B lymphocytes.

• Peptide hormones: Produced by endocrine organs.

Formed Elements: Overview

• Composed of:

  • Red blood cells (RBCs), also referred to as erythrocytes.

  • White blood cells (WBCs), known as leukocytes.

  • Platelets, referred to as thrombocytes.

• Hematopoiesis: The process of producing formed elements.

• Fractionation: Separation of whole blood for clinical analysis (i.e., hematocrit measurement).

Summary of Learning Objectives for Formed Elements

• Describe the functions of RBCs and name their oxygen-carrying protein.

• Explain hemoglobin's function and structure, especially heme units relative to oxygen transport.

• Compare Hemoglobin A with Hemoglobin F.

• Note normal hemoglobin ranges in both males and females.

• Differentiate between oxyhemoglobin and deoxyhemoglobin.

• Discuss hydroxyurea’s effect on oxygen binding in sickle cell disease.

• Elaborate on the shape of mature RBCs and its benefits.

• Approximate lifespan of RBCs and their replication ability.

Red Blood Cells

Overview

• RBCs constitute 99.9% of blood's formed elements.

• Approximately 1/3 of their volume is the protein hemoglobin (Hgb), which gives blood its color and is critical for oxygen (O2) and carbon dioxide (CO2) transport.

• Hemoglobin binds and transports O2 and CO2 and can buffer H+ ions to maintain normal blood pH.

Hemoglobin Structure

• Comprised of 4 protein chains, with each chain featuring 4 heme units containing iron (Fe) at their centers that bind oxygen.

• Each hemoglobin molecule can carry 4 Oxygen (O2) molecules.

• Hemoglobin exhibits several forms: HbA, primarily discussed here, and HbF (fetal hemoglobin), which binds O2 more tightly than HbA, enabling fetuses to extract oxygen effectively from the mother's bloodstream.

Normal Hemoglobin Values

• Adult Male: 14–18 g/dL whole blood.

• Adult Female: 12-16 g/dL whole blood.

• During oxygen binding, oxyhemoglobin is bright red, while deoxyhemoglobin (after oxygen release) appears dark red.

Hydroxyurea in Treatment

• Administering hydroxyurea enables adults with sickle cell disease to produce fetal hemoglobin (HbF) by triggering the production gene.

Structure of RBC

• RBCs exhibit a biconcave disc shape, lacking nuclei, mitochondria, and ribosomes, facilitating:

  • Increased surface area for efficient O2 absorption and release.

  • Formation into stacks for smooth passage through narrow blood vessels, especially capillaries.

  • Flexibility to adapt to various vessel diameters.

Lifespan and Energy Acquisition

• Average lifespan of RBCs is about 120 days; they lack organelles needed for repair or replication, obtaining energy through anaerobic metabolism of glucose, thereby sparing oxygen during ATP production.

• Approximately 1 million RBCs are produced per second to replace those that are removed (around 1 billion RBCs daily).

Laboratory and Clinical Analysis

Learning Objectives

• Explain measurements and normal ranges for hematocrit, hemoglobin, and RBC count.

• Identify potential reasons for abnormal test levels.

• List components found in a fractionated blood sample and identify the middle layer.

• State the functions of associated laboratory instruments for measuring hemoglobin levels, including the hemocytometer.

• Discuss physiological responses when tissue oxygen levels drop.

Anemia Testing

• Tests to detect anemia usually measure:

  • Hemoglobin in g/dL:

  • Male: 13–18 g/dL.

  • Female: 12–16 g/dL.

  • RBC Count in millions per mm³:

  • Male: 4.5–6.3 million/mm³.

  • Female: 4.2–5.5 million/mm³.

  • Hematocrit percentage, also known as packed cell volume (PCV):

  • Male: 40–54%.

  • Female: 37–47%.

Hematocrit Measurement

• Hematocrit determines the volume of cellular material in whole blood, reported as a percentage. During fractionation, WBCs and platelets form a thin layer called the BUFFY COAT between the plasma and formed elements.

Blood Testing Instruments

• Hemoglobin Meter: Used to measure hemoglobin concentrations (grams of Hb per 100 ml).

• Hemocytometer: Utilized to count cells, including WBCs and assess their differential count.

Gas Exchange and Anemia

Movement of Gases

• In tissues, where [O2] is low and [CO2] is high, hemoglobin releases O2 and binds CO2, forming carbaminohemoglobin.

• Lungs maintain high [O2] and low [CO2], facilitating gas exchange. In anemia, impaired oxygen delivery is reflected in hemoglobin and RBC count metrics.

Causes of Anemia

• Various causes leading to anemia include:

  • Iron Deficiency: Essential for oxygen binding.

  • RBC Loss: Through bleeding and hemorrhage.

  • Inability to Produce RBCs: Resulting from bone marrow or kidney failures:

  • Aplastic anemia (bone marrow failure)

  • Erythropoietin (EPO) deficiency due to kidney failure affects RBC stimulation.

  • Genetic Factors: Can lead to disorders such as sickle cell anemia and thalassemia with abnormal hemoglobin structures.

  • Autoimmune Factors: Cause conditions such as pernicious anemia due to immune destruction of stomach cells that produce Intrinsic Factor (IF), necessary for vitamin B12 absorption.

Red Blood Cell Lifecycle

Development Stages

• Red Blood Cell Maturation:

  • Takes about 5-7 days and includes:

  1. Hemocytoblast

  2. Myeloid stem cell

  3. Proerythroblast

  4. Erythroblast

  5. Reticulocyte

  6. Mature RBC

Nutrient Requirements

• To produce healthy RBCs, the following are required:

  • Amino acids

  • Iron

  • Vitamins B12 (from meats/dairy), B6, and Folic acid.

• Pernicious anemia: Characterized by vitamin B12 deficiency, leading to severe neurological symptoms due to lack of IF necessary for B12 absorption.

Hormonal Control of Erythropoiesis

• Erythropoietin (EPO): A hormone produced primarily in kidneys (85%) and liver (15%), secreted in response to low oxygen levels in peripheral tissues. EPO stimulates RBC production from bone marrow.

Erythrocyte Homeostasis

• RBC count is maintained through negative feedback. For example, a drop in RBC count results in hypoxemia (oxygen deficiency), prompting an increase in EPO output from kidneys, which elevates RBC production in 3 to 4 days to restore oxygen levels.

• Factors leading to hypoxemia include blood loss, high altitude, increased exercise, or lung tissue loss in diseases such as emphysema.

Learning About Blood Groups and Compatibility

Key Terminology

• Antigen/Agglutinogen: Molecules on the membrane of RBCs identifying the blood type.

• Blood type determination involves the presence or absence of surface antigens A, B, and Rh.

Blood Type Antigens and Antibodies

• Types of blood Groups:

  • Type A: RBCs with surface antigen A, anti-B antibodies present in plasma.

  • Type B: RBCs with surface antigen B, anti-A antibodies present in plasma.

  • Type AB: RBCs have both A and B antigens, no antibodies in plasma.

  • Type O: RBCs lack A and B antigens, possess both anti-A and anti-B antibodies.

Hemolytic Disease of the Newborn (HDN)

• HDN occurs when an Rh-negative mother gives birth to an Rh-positive child without administration of Rhogam, leading to the mother producing antibodies against Rh antigens, which can attack the fetus's blood cells. This can lead to serious complications during subsequent pregnancies if not managed.

Universal Donors and Recipients

• Type O- is recognized as the universal packed red blood cell donor, while Type AB+ is recognized as the universal recipient.

• In plasma transfusions, Type AB is the universal plasma donor, and Type O is the universal plasma recipient.

White Blood Cells (WBCs)

Overview

• WBCs, or leukocytes, are complete cells without hemoglobin, comprising:

  • Protective function against pathogens.

  • Removal of toxins and wastes.

  • Attack on abnormal cells.

  • Divided into granulocytes (with visible granules) and agranulocytes (where granules are challenging to see).

• Commonly found in connective tissue and lymphoid organs, circulation counts range 5000 to 10,000/mm³.

Characteristics

• WBCs migrate out of the bloodstream via margination (adhesion to vessel walls) and emigration (diapedesis), supported by positive chemotaxis (attraction to chemical signals at injury/infection sites).

• Major WBC types include:

  • Neutrophils

  • Eosinophils

  • Basophils

  • Monocytes

  • Lymphocytes

Specifics of WBC Functions

• Neutrophils: First responders to infection, employing phagocytosis and releasing enzymes that lead to inflammation. They can undergo degranulation and respiratory burst, releasing substances like prostaglandins and leukotrienes for immune response and recovery.

• Eosinophils: Fight parasitic infections and moderate allergic reactions while secreting nitric oxide and enzymes to counteract inflammation.

• Basophils: Release histamine (promotes vasodilation and enhances WBC delivery) and heparin (prevents clot formation that may hinder WBC movement).

• Monocytes: Transform into macrophages in peripheral tissues, contributing significantly to phagocytic activity and immune signaling.

• Lymphocytes: Component of the specific defense, primarily divided into:

  • T cells: Cell-mediated immunity.

  • B cells: Humoral immunity, differentiating into plasma cells to produce antibodies.

  • Natural Killer (NK) cells: Attack and destroy abnormal tissues, including cancer cells.

WBC Disorders

• Leukopenia: Abnormally low WBC count, often due to radiation or infectious disease exposure.

• Leukocytosis: An elevated WBC count commonly associated with infection, allergy, or disease, while leukemia signifies an extremely high count, typically involving abnormal or immature WBCs.

Stages of WBC Production

• All blood cells arise from hemocytoblasts, which produce two stem cell lines:

  • Myeloid stem cells lead to all WBCs except lymphocytes, maturing entirely in bone marrow.

  • Lymphoid stem cells migrate to lymphoid tissues for lymphocyte production.

Regulation of WBC Production

• Governed by colony-stimulating factors (CSFs) that facilitate leukocyte production:

  1. M-CSF: Promotes monocyte formation.

  2. G-CSF: Enhances granulocyte (neutrophils, eosinophils, basophils) production.

  3. GM-CSF: Stimulates both granulocytes and monocytes.

  4. Multi-CSF: Accelerates production of various blood components, including granulocytes and RBCs.

Platelets and Hemostasis

Platelet Characteristics

• Platelets are key cellular fragments in the clotting system, circulating for 9–12 days and primarily removed by the spleen.

• Normal platelet count: 150,000 to 500,000/mm³, average around 150,000/mm³.

  • Thrombocytopenia: Abnormally low platelet count leading to bleeding issues promotes greater disease vulnerability.

  • Thrombocytosis: An elevated platelet count often due to infections or inflammation, can surpass 1 million platelets/mm³.

Functions of Platelets

• Key roles include:

  • Secretion of vasoconstrictors to reduce blood loss.

  • Aggregation to form plugs at injury sites.

  • Release of clotting factors and enzymes that initiate clotting and wound repair processes.

  • Phagocytosis of bacteria and secretion of growth factors.

Hemostasis Phases

• Vascular Phase: Lasts approximately 30 minutes post-injury, where endothelial cells release endothelins leading to vasoconstriction and enhanced blood flow regulation.

• Platelet Phase: Initiated by platelets adhering to the tissue and each other, promoting aggregation, vasoconstriction, and clotting.

• Coagulation Phase: Complex cascade converting soluble fibrinogen to insoluble fibrin, ultimately leading to clot formation and sealing off the vessel damage. Details include the roles of intrinsic and extrinsic pathways and their dependencies on clotting factors and calcium ions.

Feedback Control in Hemostasis

• Positive feedback ensures the rapid response during hemostasis until the initial injury is sealed.

• Clotting factors include compounds for regulation:

  • Anticoagulants play a role in inhibiting clot formation, including agents like antithrombin-III and heparin.

  • Endothelial derived factors that maintain balance against excessive clotting.

Summary of Clotting Factors

Clotting Test Procedures

• Coagulation Time: Measures the duration for blood to clot, averaging 8-18 minutes.

• Bleeding Time: Time needed for a small puncture to stop bleeding, typically around 1-4 minutes.