Overview of Blood and Circulatory System

Blood: Components, Functions, Disorders, and Typing

Circulatory System Overview

  • Components: Consists of the heart (pump), blood vessels, and blood.

  • Functions:

    • Picks up nutrients from the digestive system.

    • Exchanges gases with the respiratory system.

    • Delivers nutrients and O_2 to every cell.

    • Carries CO_2 to lungs for removal.

    • Carries wastes and excess water to the urinary system.

    • Carries metabolic wastes to the liver for removal.

  • Interconnected Systems (Figure 7.1): The circulatory system acts as a transport system connecting the respiratory system (intake of O2, elimination of CO2), digestive system (food and water intake, nutrient absorption), and urinary system (elimination of excess water, salts, metabolic wastes) to all cells of the human body for transport to and from.

The Components and Functions of Blood

  • Blood Defined: A specialized connective tissue.

  • Composition: Consists of specialized cells and cell fragments, suspended in a watery solution of ions and molecules.

  • Three Primary Functions:

    1. Transportation: Of nutrients, waste products, and hormones throughout the body.

    2. Regulation: Maintenance of body temperature, water volume, and pH balance.

    3. Defense: Protection against infections (via immune cells) and prevention of bleeding (via clotting mechanisms).

Composition of Whole Blood

  • Whole blood is separated into two main components upon centrifugation:

    • Plasma: Makes up 55% of whole blood.

    • Formed Elements (Cells): Makes up 45% of whole blood.

      • Red Blood Cells (RBCs)

      • White Blood Cells (WBCs)

      • Platelets

Plasma

  • Definition: The liquid portion of the blood.

  • Composition (Figure 7.2, Table 7.1):

    • Water (90%): Acts as a solvent for carrying other substances.

    • Electrolytes (Salts): Include sodium, potassium, calcium, magnesium, chloride, bicarbonate.

      • Functions: Osmotic balance, pH buffering, control of cell function and volume, electrical charge across cells, and function of excitable cells (nerve and muscle). Essential for homeostasis.

    • Plasma Proteins:

      • Albumins: Maintain osmotic balance with interstitial fluid, transport electrolytes, hormones, and wastes. Constitute the largest percentage of plasma proteins.

      • Globulins: A diverse group of proteins.

        • Alpha & Beta Globulins: Important transport functions; bind to lipids forming lipoproteins ($\text{HDL}$ - high density lipoproteins, $\text{LDL}$ - low density lipoproteins).

        • Gamma Globulins: Act as antibodies, crucial for the body's defenses against infections.

      • Clotting Proteins (e.g., Fibrinogen): Contribute to blood clotting.

    • Hormones: Chemical messenger molecules (e.g., insulin, growth hormones, testosterone, estrogen) that regulate specific body functions.

    • Gases: O2 (needed for metabolism) and CO2 (waste product of metabolism) are dissolved in plasma, in addition to being carried by RBCs.

    • Nutrients and Wastes: Substances transported including glucose, fatty acids, vitamins, amino acids, urea, uric acid, and heat.

Formed Elements (Cells)
1. Red Blood Cells (Erythrocytes)

  • Number: Approx. 4-6 million per mm^3 of blood. Make up almost half the blood volume (44% of whole blood, Figure 7.2).

  • Functions: Primarily transport oxygen (O2) to body tissues and help transport carbon dioxide (CO2) away from tissues.

  • Hemoglobin:

    • RBCs are packed with hemoglobin, the protein responsible for O_2 transport (Figure 7.3, 7.4).

    • Each hemoglobin molecule includes four heme groups, each containing an iron atom to which O_2 binds.

  • Origin: Stem cells in the bone marrow.

  • Abundance: Outnumber White Blood Cells (WBCs) by a ratio of roughly 1000:1.

  • Life Span: About 120 days in humans.

  • Control of Production: Regulated by the hormone erythropoietin (EPO).

Hematocrit and Hemoglobin Measurements

  • Hematocrit: The percentage of whole blood volume that consists of red blood cells.

    • Men: 43-49%

    • Women: 37-43%

  • Hemoglobin Measurement: The concentration of hemoglobin in blood.

    • Men: 14-18 gm%

    • Women: 12-14 gm%

  • Clinical Significance:

    • Low hematocrit or hemoglobin may indicate anemia (reduced oxygen-carrying capacity).

    • High hematocrit may be a response to high elevation (less O_2 available).

    • Very high hematocrit is risky due to increased blood viscosity, making the heart work harder.

Red Blood Cell Life Cycle (Figure 7.5)

  • Production: Stem cells in the red bone marrow develop into erythroblasts.

  • Maturation: Erythroblasts fill with hemoglobin, mature into red blood cells, and discard their nucleus and organelles, resulting in a biconcave disc shape.

  • Removal: Aged RBCs are removed from circulation by macrophages (large phagocytic cells) primarily in the liver and spleen.

  • Recycling: Iron and amino acids from the broken-down hemoglobin are recycled.

  • Bilirubin Formation: The heme group (minus the iron) is converted to bilirubin, which is then discarded through the digestive tract.

Regulation of RBC Production (Figure 7.6)

  • Negative Feedback Loop: RBC number is maintained by a negative feedback mechanism.

  • Kidney's Role: Special oxygen-sensitive cells in the kidneys monitor O2 availability. If O2 levels are low, these cells secrete the hormone erythropoietin (EPO).

  • EPO's Action: EPO stimulates stem cells in the bone marrow, leading to an increase in red blood cell production.

  • Clinical Relevance: In cases of kidney disease, inadequate EPO secretion can lead to anemia, requiring EPO supplementation. Some athletes have abused EPO by injecting it to increase RBC production, which can dangerously increase blood viscosity and strain the heart.

2. White Blood Cells (Leukocytes)

  • Origin: Arise from the division of stem cells in the bone marrow (Figure 7.5).

  • Number: Approx. 4000-11,000 per mm^3 of blood. Make up about 1% of whole blood.

  • Functions:

    • Protection from infection by invading organisms and abnormal cells.

    • Regulation of the inflammatory reaction.

  • General Types: Leukocytes are categorized into two main groups based on the presence or absence of visible granules in their cytoplasm:

    • Granular Leukocytes: Neutrophils, Eosinophils, and Basophils.

    • Agranular Leukocytes: Lymphocytes and Monocytes.

Granular Leukocytes

  • Neutrophils:

    • Constitute about 60% of circulating WBCs (5400 per mm^3).

    • First on the scene to fight infection by engulfing (phagocytizing) microorganisms. Possess a lobed nucleus and fine granules.

  • Eosinophils:

    • Constitute about 2-4% of circulating WBCs (275 per mm^3).

    • Defend against large parasites (e.g., worms).

    • Moderate the severity of allergic reactions. Possess a lobed nucleus and red or yellow granules. May phagocytize antigen-antibody complexes.

  • Basophils:

    • Constitute about 0.5% of circulating WBCs (35 per mm^3).

    • Contain histamine in their granules, playing a role in inflammation and allergic reactions. Possess an obscure nucleus and large purple granules. Release heparin, histamine, and serotonin.

Agranular Leukocytes

  • Monocytes:

    • Constitute about 5% of circulating WBCs (540 per mm^3).

    • Leave the blood and transform into macrophages, which are powerful phagocytic cells. Possess a kidney-shaped nucleus.

  • Lymphocytes:

    • Constitute about 30% of circulating WBCs (2750 per mm^3).

    • Play a large role in the immune response. Possess a round nucleus and little cytoplasm.

    • Two main types:

      • B lymphocytes: Produce antibodies.

      • T lymphocytes: Destroy specific target cells.

3. Platelets

  • Origin: Arise from megakaryocytes, which are large cells that develop from stem cells in the bone marrow (Figure 7.5).

  • Formation: Megakaryocytes fragment into small pieces known as platelets.

  • Number: Approx. 250,000-500,000 per mm^3 of blood.

  • Function: Play a crucial role in hemostasis (stopping blood loss) and blood clotting.

    • If a blood vessel is injured, platelets initiate the clotting process by forming a plug.

    • Platelets also participate in the repair process of damaged vessels.

Hemostasis: Stopping Blood Loss (Figure 7.8)

Hemostasis involves three main stages to prevent excessive blood loss from an injured blood vessel:

  1. Vascular Spasm: Immediate constriction of the injured blood vessel. This reduces blood flow to the damaged area.

  2. Platelet Plug Formation: Platelets adhere to the exposed collagen in the damaged vessel wall and to each other, forming a temporary seal (platelet plug) over the rupture.

  3. Coagulation (Blood Clot Formation): A complex series of reactions, involving at least 12 different clotting proteins (factors) in the plasma, leading to the transformation of blood from a liquid to a gel (blood clot).

Mechanism of Blood Clot Formation

  • Damage to blood vessels initiates the process.

  • Platelets release prothrombin activator.

  • Prothrombin activator converts prothrombin (an inactive plasma protein) into thrombin (an active enzyme).

  • Thrombin, in turn, converts fibrinogen (a soluble plasma protein) into insoluble fibrin fibers.

  • A mass of fibrin, platelets, and trapped red blood cells forms the definitive blood clot.

  • The clot subsequently contracts and tightens, pulling the edges of the damaged vessel together.

Clotting Disorders

  • Bleeding Disorders:

    • Hemophilia: A deficiency of one or more clotting proteins.

      • Hemophilia A: Specifically a lack of clotting factor VIII.

      • Modern treatment involves supplementing with Factor VIII, often produced by genetic engineering.

    • Medication Interference: Some medications, such as aspirin, can interfere with hemostasis by inhibiting platelet aggregation.

Human Blood Types

  • Blood Transfusion: The administration of blood directly into the bloodstream of another person.

  • Compatibility: Success depends critically on matching the blood type of the donor with that of the recipient to prevent adverse reactions.

  • Primary Systems: The two major blood typing systems are ABO blood types (A, B, AB, and O) and Rh factors (Rh-positive and Rh-negative).

Key Definitions

  • Antigen: A non-self protein, or any substance foreign to the body, that can trigger an immune response. Antigens can be found on cells from another individual (e.g., blood cells) or on the cells of invading microorganisms (e.g., bacteria, viruses).

  • Antibody: A defensive protein produced by the body's immune system, specifically directed against particular antigens. Antibodies are gamma globulins found in the plasma.

    • Many antibodies target infectious microbes.

    • Other antibodies can target antigens found on transfused blood cells, causing a severe reaction (agglutination or clumping) and inactivating antigen-bearing cells (Figure 7.11).

  • Agglutination: The clumping of antigen-bearing cells by antibodies. This effectively inactivates the foreign cells.

ABO Blood Typing (Figure 7.12)

  • Basis: Determined by the presence or absence of specific antigens (A and B) on the surface of red blood cells.

  • Antibody Production: Individuals naturally produce antibodies against the A or B antigens that are not present on their own red blood cells.

  • Compatibility Rule: The recipient of a blood transfusion must not receive cells that carry antigens against which they have antibodies. If incompatible blood is transfused, a severe and potentially fatal reaction (agglutination, hemolysis) can occur.

  • Blood Types and Compatibility:

    • Type A Blood: Has A antigens on RBCs and anti-B antibodies in plasma. Can receive A or O blood.

    • Type B Blood: Has B antigens on RBCs and anti-A antibodies in plasma. Can receive B or O blood.

    • Type AB Blood: Has both A and B antigens on RBCs and neither anti-A nor anti-B antibodies in plasma. Can receive A, B, AB, or O blood. Considered the