Blood Composition and Functions

• Blood is a specialized connective tissue containing cells suspended in a fluid matrix.
• Blood, composed of plasma and formed elements, provides transport, regulation, and protective services to the body.
• The cardiovascular system consists of a pump (the heart), a series of conducting hoses (blood vessels), and fluid connective tissue (blood).

Functions of Blood

• Transports dissolved gases, nutrients, hormones, and metabolic wastes.
• Regulates pH and ion composition of interstitial fluids.
• Restricts fluid losses at injury sites.
• Defends against toxins and pathogens.
• Stabilizes body temperature.

Characteristics of Blood

• Blood temperature is around 38°C (100.4°F).
• Blood has high viscosity.
• Blood is slightly alkaline, with a pH between 7.35 and 7.45.
• Blood volume is 7% of body weight in kilograms; a 75-kg (165-lb) person has approximately 5.25 liters (5.4 quarts) of blood.

Whole Blood Components

• Plasma: Fluid containing many proteins.
• Formed elements: Cells and cell fragments.
• Fractionation: Process of separating whole blood into plasma and formed elements.

Plasma

• Makes up about 55% of blood volume.
• More than 90% of plasma is water, also containing dissolved plasma proteins and other solutes.
• Plasma has a similar composition to interstitial fluid because water, ions, and small solutes are exchanged across capillary walls.

Plasma Proteins

• Albumins (60%): Major contributors to plasma osmolarity, and transport fatty acids, thyroid hormones, and some steroid hormones.
• Globulins (35%): Includes antibodies (immunoglobulins), transport globulins for hormone-binding, metalloproteins, apolipoproteins, and steroid-binding proteins.
• Fibrinogen (4%): Soluble protein that functions in clotting; converts to insoluble fibrin, and its conversion leaves serum in a blood sample.
• Other plasma proteins (1%): Include varying concentrations of enzymes and hormones.

Origins of Plasma Proteins

• More than 90% are made in the liver, including all albumins, fibrinogen, most globulins, and various proenzymes.
• Antibodies are made by plasma cells.
• Peptide hormones are made by endocrine organs.

Formed Elements

• Red blood cells (erythrocytes)
• White blood cells (leukocytes)
• Cell fragments (platelets/thrombocytes)
• Hemopoiesis is the process of producing formed elements.

Red Blood Cells (RBCs)

• Also called erythrocytes, formed by erythropoiesis, and contain hemoglobin that transports respiratory gases.
• Make up 99.9% of formed elements.
• Hemoglobin: Red pigment that gives whole blood its color, binds, and transports oxygen and carbon dioxide.
• RBC Count: the number of RBCs per microliter of whole blood.
  • Adult male: 4.5-6.3 million
  • Adult female: 4.2-5.5 million
• Hematocrit: Percentage of formed elements in blood, packed cell volume (PCV).
  • Adult male: 46
  • Adult female: 42

Structure of RBCs

• Small, highly specialized cells.
• Biconcave discs: thin central region and thicker outer margin.

Function of RBC Structure

• Large surface-area-to-volume ratio allows quick absorption and release of oxygen.
• Rouleaux (formed stacks) allow smooth blood flow through narrow blood vessels.
• RBCs bend and flex when entering small capillaries, where a 7.8-µm RBC can pass through a 4-µm capillary.

Mature RBCs

• Anucleate: lack nuclei.
• Lack mitochondria and ribosomes.
• These lack the ability to divide, synthesize proteins, or repair damage, and live about 120 days.

Hemoglobin (Hb or Hgb)

• Protein in RBCs that transports respiratory gases.
• Normal hemoglobin levels:
  • Adult male: 14–18 g/dL whole blood
  • Adult female: 12–16 g/dL whole blood
• Has a complex quaternary structure with four globular protein subunits, each with one molecule of heme.
• Each heme contains one iron ion that interacts with oxygen to form oxyhemoglobin (HbO2) or dissociates to form deoxyhemoglobin.

Fetal Hemoglobin

• Form of hemoglobin in embryo or fetus.
• Binds oxygen more readily than adult hemoglobin.
• Takes up oxygen from maternal blood at placenta.

Hemoglobin Function

• Each RBC contains about 280 million Hb molecules.
• Each RBC can carry over a billion molecules of O2. Where oxygen is low, in peripheral capillaries, hemoglobin releases O2, and binds CO2, forming carbaminohemoglobin.
• At the lungs, where O2 is high, hemoglobin binds oxygen and releases CO2.
• Anemia results when hematocrit or Hb content of RBCs is reduced, and interferes with oxygen delivery to peripheral tissues.

RBC Formation and Turnover

• 1% of circulating RBCs are replaced per day, which equates to about 3 million new RBCs entering the bloodstream each second.
• Erythropoiesis: red blood cell formation.
• In embryos, embryonic blood cells move from the bloodstream to the liver, spleen, thymus, and bone marrow, and differentiate into stem cells that divide to produce blood cells.
• In adults, erythropoiesis occurs only in myeloid tissue, which is red bone marrow.
• Hemocytoblasts, also called hematopoietic stem cells (HSCs), are stem cells in myeloid tissue that divide to produce...
  • Myeloid stem cells that become RBCs and some WBCs.
  • Lymphoid stem cells that become lymphocytes.
• Hematologists have identified several stages of RBC maturation.
  • Myeloid stem cell
  • Proerythroblast
  • Erythroblast stages
  • Reticulocyte
  • Mature RBC
• Erythropoietin (EPO): hormone that stimulates erythropoiesis.
  • Secreted by kidneys and liver when oxygen in peripheral tissues is low (hypoxia).
• Blood doping: re-infusing packed RBCs to elevate hematocrit. A dangerous practice used by some athletes.
• Erythropoiesis requires amino acids, iron, folic acid, and vitamins B12 and B6.
• Pernicious anemia: Lack of vitamin B12.

Hemoglobin Recycling

• Macrophages of spleen, liver, and red bone marrow engulf aged RBCs.
• Remove Hb molecules from hemolyzed RBCs, breaking Hb into components, but only the iron of each heme unit is recycled.
• Hemoglobinuria: red or brown urine due to abnormally high hemolysis in bloodstream.
• Hematuria: whole RBCs in urine due to kidney or blood vessel damage.
• Iron is removed from each heme unit, forming green biliverdin, which converts to orange-yellow bilirubin (excreted by liver in bile).
• Jaundice is caused by a buildup of bilirubin.
• Intestinal bacteria converts bilirubin to urobilins and stercobilins, where urobilins make urine yellow and stercobilins make feces brown.

Iron Recycling

• Iron is removed from heme, being bound and stored in a phagocytic cell, or released into bloodstream.
• In bloodstream, iron is bound to transferrin.
• Developing RBCs in red bone marrow absorb transferrins and use them to synthesize Hb.
• Excess transferrins are removed in liver and spleen, storing iron in ferritin and hemosiderin.

The ABO and Rh Blood Groups

• Groups are based on antigen-antibody responses.
• Surface antigens are substances on plasma membranes that identify cells to the immune system.
• Normal cells are ignored and foreign cells are attacked.
• Blood type is determined by presence or absence of surface antigens on RBCs: A, B, and Rh (or D).
• Four blood types:
  • Type A (surface antigen A)
  • Type B (surface antigen B)
  • Type AB (antigens A and B)
  • Type O (neither A nor B)
• Rh blood group is based on presence or absence of Rh antigen.
  • Rh positive (Rh+): Rh surface antigen is present (e.g., Type O+). -Rh negative (Rh−): Rh antigen is absent (e.g., Type O-).
• Agglutinogens are surface antigens on RBCs, which are screened by the immune system.
• Agglutinins are antibodies in plasma that attack antigens on foreign RBCs, and cause agglutination (clumping) of foreign cells.
• Blood types and their agglutinins:
  • Type A: anti-B antibodies
  • Type B: anti-A antibodies
  • Type O: both anti-A and anti-B antibodies
  • Type AB: neither anti-A nor anti-B antibodies
• Cross-reaction (transfusion reaction) may occur in a transfusion of blood or plasma from one person to another, and occurs if donor and recipient blood types are NOT COMPATIBLE.
• Plasma antibody meets its specific surface antigen, RBCs agglutinate, and may hemolyze.
• Compatibility testing is performed in advance of transfusions.
• Cross-match testing reveals cross-reactions between donor's RBCs and a recipient's plasma.
• Type O- is the universal donor.
• Type AB+ is the universal recipient.
• Cross-reactions can still occur because at least 48 surface antigens exist besides A and B.

White Blood Cells (WBCs)

• Also called leukocytes, contribute to the body’s defense.
• Have nuclei and other organelles.
• Lack hemoglobin.
• WBC Function: defending the body against pathogens, removing toxins and wastes, and attacking abnormal or damaged cells.
• Most WBCs are located in connective tissue proper and organs of the lymphatic system.
• A small fraction of WBCs circulates in blood about 5000 to 10,000 per microliter.

Characteristics of Circulating WBCs

• All can migrate out of bloodstream.
• All are capable of amoeboid movement.
• Positive chemotaxis: all are attracted to specific chemical stimuli.
• Some are phagocytic.

Types of WBCs

• Neutrophils
• Eosinophils
• Basophils
• Monocytes
• Lymphocytes
• WBCs are grouped into two classes: granulocytes and agranulocytes.

Granulocytes

• Neutrophils (neutral pH stain):
• Also called polymorphonuclear leukocytes and make up 50–70% of circulating WBCs.
• Pale cytoplasmic granules containing Lysosomal enzymes and Bactericidal (bacteria-killing) compounds.
• Very active, phagocytic cells that attack and digest bacteria.
• Degranulation: reduction in number of cytoplasmic granules that occurs when a vesicle containing a pathogen fuses with lysosomes containing enzymes and defensins. They release prostaglandins and leukotrienes, living in bloodstream for 10 hours or less.
• Dead neutrophils contribute to pus.
• Eosinophils (acidic pH stains them reddish):
  • Also called acidophils, making up 2-4% of circulating WBCs.
  • Engulf bacteria, protozoa, and cellular debris.
• Attack large parasites by releasing toxic compounds (such as nitric oxide, and cytotoxic enzymes), being sensitive to allergens.
• Basophils (basic pH stains them blue-blackish):
  • Less than 1% of circulating WBCs.
  • Cross capillary endothelium and accumulate in damaged tissues.
• Agranulocytes: release histamines that dilate blood vessels, and heparin to prevent blood clotting.
• Monocytes
  • large, spherical cells, making up 2-8% of circulating WBCs.
  • Remain in bloodstream for 24 hours, then enter peripheral tissues to become macrophages.
• Aggressive phagocytes that engulf large pathogens.
• Release chemicals that attract other phagocytic cells and fibroblasts to injured area.
• Three Classes of Lymphocytes:
  • T cells (T lymphocytes): cell-mediated immunity that attacks foreign cells or control other lymphocytes.
  • B cells (B lymphocytes): humoral immunity; differentiate into plasma cells, which synthesize antibodies.
  • Natural killer (NK) cells detect and destroy abnormal cells.
• Differential count of WBC population can detect infection, inflammation, and allergic reactions.

WBC Disorders

• Leukopenia: low WBC count.
• Leukocytosis: high WBC count.
• Leukemia: cancer of WBCs indicated by extreme leukocytosis.
• Leukopoiesis is WBC production.
  • Hemocytoblasts produce myeloid stem cells and lymphoid stem cells.
  • Myeloid stem cells divide to produce progenitor cells, giving rise to all formed elements except lymphocytes.
• Lymphocytopoiesis is the production of lymphocytes from lymphoid stem cells.
• WBC Development: some lymphoid stem cells remain in red bone marrow and differentiate into B cells or natural killer cells.
• Others migrate from red bone marrow to peripheral lymphatic tissues, such as the thymus, spleen, and lymph nodes, where lymphocytes are produced (T cells are produced in the thymus).
• Colony-stimulating factors (CSFs) are hormones that regulate WBC populations.
  • Multi-CSF accelerates production of granulocytes, monocytes, platelets, and RBCs.
  • GM-CSF stimulates granulocyte and monocyte production.
  • G-CSF stimulates granulocyte production.
  • M-CSF stimulates monocyte production.

Platelets

• Platelets (thrombocytes) are disc-shaped cell fragments that function in the clotting process.
• They circulate for 9-12 days, are removed by phagocytes (mainly in the spleen), 150,000 to 500,000 per microliter of blood.
• One-third of platelets in blood are stored in vascular organs like the spleen, and are mobilized during a circulatory crisis.
• Functions of Platelets:
  • Release important clotting chemicals.
  • Temporarily patch damaged vessel walls.
  • Reduce size of break in vessel wall.
• Thrombocytopoiesis: platelet production that occurs in red bone marrow.
• Megakaryocytes: giant cells in red bone marrow, and produce platelets by shedding membrane-enclosed packets of cytoplasm.
• Hormonal Control of Platelet Production:
  • Thrombopoietin (TPO)
  • Interleukin-6 (IL-6)
  • Multi-CSF

Hemostasis

• Hemostasis: the process of blood clotting, or hemostasis, stops blood loss.
• Hemostasis has three phases:
  • Vascular phase
  • Platelet phase
  • Coagulation phase

Vascular Phase

• A cut triggers vascular spasm, the contraction of smooth muscle fibers of vessel wall that lasts about 30 minutes.
• Changes in Endothelium During Vascular Phase include:
  • Endothelial cells contracting and exposing basement membrane to bloodstream.
  • Endothelial cells releasing ADP, tissue factor, prostacyclin, and endothelins (peptide hormones).
• Endothelins cause smooth muscle contraction and cell division.
• Endothelial plasma membranes become “sticky”, sealing off the tear and preventing blood flow.

Platelet Phase

• Platelet adhesion: platelets attach to exposed surfaces.
• Platelet aggregation: platelets stick to each other, beginning within 15 seconds after injury. Forms a platelet plug that closes small breaks.
• Activated platelets release clotting compounds including adenosine diphosphate (ADP), thromboxane A2 and serotonin, clotting factors, platelet-derived growth factor (PDGF), and calcium ions.
• Factors that Limit Growth of Platelet Plug:
  • Prostacyclin inhibits platelet aggregation.
  • Inhibitory compounds released by WBCs.

Coagulation Phase

• Begins 30 seconds or more after injury.
• Depends on clotting factors (procoagulants): Ca2+ and 11 different proteins.
• Proenzymes: inactive enzymes converted to active enzymes that direct reactions in clotting response.
• Involves chain reactions of three pathways:
  • Extrinsic pathway
  • Intrinsic pathway
  • Common pathway

Extrinsic Pathway

• Damaged endothelial calls or peripheral tissues release Factor III (tissue factor).
• Enzyme complex activates Factor X.

Intrinsic Pathway

• Begins with activation of proenzymes exposed to collagen fibers at injury site.
• Platelets release PF-3.
• Enzyme complex activates Factor X.

Common Pathway

• Begins with activation of Factor X.
• Factor X activates prothrombin activator.
• Prothrombin (proenzyme) to thrombin.
• Thrombin converts fibrinogen to insoluble fibrin, producing a blood clot.
• Thrombin generated in the common pathway stimulates formation of tissue factor and release of PF-3 by platelets, forming a positive feedback loop that accelerates the clotting process.
• Feedback Control of Blood Clotting from Anticoagulants (enzymes that inhibit clotting), such as Antithrombin-III.
• Heparin accelerates activation of antithrombin-III.
• Thrombomodulin activates protein C, which inactivates clotting factors and stimulates formation of plasmin.
• Prostacyclin inhibits platelet aggregation and opposes factors.
• Calcium ions and vitamin K are essential to clotting process where all three pathways require Ca2+ and vitamin K is required for synthesis of four clotting factors.
• Bleeding and clotting extremes: thrombocytopenia, hemophilia, thrombophilia, and deep vein thrombosis (DVT).
• Clot retraction is the process that pulls torn edges of vessel closer together.
• Reduces residual bleeding.
• Stabilizes injury site.
• Reduces size of damaged area.
• Clot retraction makes it easier for fibroblasts, smooth muscle cells, and endothelial cells to complete repairs.

Explore the components and vital roles of blood, including plasma proteins, formed elements, and blood volume regulation. Understand the primary functions of blood in transporting substances, defending against pathogens, and maintaining homeostasis. Learn about the consequences of impaired albumin production and compensatory mechanisms for decreased erythrocyte production.