Blood components and functions

• Blood is a fluid connective tissue composed of plasma and formed elements, providing transport, regulation, and protective services.

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

• Temperature is around 38°C (100.4°F).
• Has high viscosity.
• Is slightly alkaline (pH 7.35-7.45).
• Blood volume is about 7% of body weight in kilograms; a 75-kg person has approximately 5.25 liters.

Whole Blood Components

• Plasma, which is a fluid containing many proteins.
• Formed elements, including cells and cell fragments.
• Fractionation separates whole blood into plasma and formed elements.

Plasma

• Comprises about 55% of blood volume.
• Over 90% is water, containing dissolved plasma proteins and other solutes.
• Similar in composition to interstitial fluid due to the exchange of water, ions, and small solutes across capillary walls.

Plasma Proteins

• Albumins (60%) are major contributors to plasma osmolarity and transport fatty acids, thyroid hormones, and some steroid hormones.
• Globulins (35%) include antibodies (immunoglobulins) and transport globulins for hormones, metalloproteins, and steroids.
• Fibrinogen (4%) is a soluble protein functioning in clotting; its conversion to fibrin leaves serum.
• Other plasma proteins (1%) vary in concentrations of enzymes and hormones.
• Over 90% of plasma proteins are made in the liver, including albumins, fibrinogen, most globulins, and various proenzymes, while antibodies are made by plasma cells, and peptide hormones by endocrine organs.

Formed Elements

• Erythrocytes (red blood cells)
• Leukocytes (white blood cells)
• Thrombocytes (cell fragments/platelets)
• Hemopoiesis is the process of producing formed elements.

Red Blood Cells (RBCs)

• Erythrocytes contain hemoglobin for transporting respiratory gases.
• RBCs make up 99.9% of formed elements.
• Hemoglobin, a red pigment, binds and transports oxygen and carbon dioxide giving whole blood its color.
• RBC count varies, with adult males at 4.5-6.3 million and adult females at 4.2-5.5 million per microliter.
• Hematocrit, percentage of formed elements, is 46 for adult males and 42 for adult females.

Structure of RBCs

• Small, highly specialized biconcave discs, thin in the central region and thicker at the outer margin.
• A large surface-area-to-volume ratio allows quick absorption and release of oxygen.
• Rouleaux formations allow smooth blood flow through narrow vessels and capillaries
• 7.8-µm RBCs can pass through 4-µm capillaries due to their flexibility.
• Mature RBCs lack nuclei, mitochondria, and ribosomes, and cannot divide, synthesize proteins, or repair damage with a lifespan around 120 days.

Hemoglobin (Hb or Hgb)

• Protein in RBCs that transports respiratory gases.
• Normal hemoglobin levels: 14–18 g/dL in adult males and 12–16 g/dL in adult females.
• Has a complex quaternary structure with four globular protein subunits (two alpha and two beta chains), and each with one molecule of heme containing one iron ion
• Iron interacts with oxygen to form oxyhemoglobin (HbO2) but can dissociate easily to form deoxyhemoglobin.
• Fetal hemoglobin binds oxygen more readily than adult hemoglobin, facilitating oxygen uptake from maternal blood. Each RBC contains about 280 million Hb molecules, enabling each RBC to carry over a billion molecules of O2.

Hemoglobin Function

• In peripheral capillaries where O2 is low, hemoglobin releases O2 and binds CO2, forming carbaminohemoglobin.
• At the lungs where O2 is high, hemoglobin reversibly binds O2
• Anemia results when hematocrit or Hb content of RBCs is reduced, which interferes with oxygen delivery to peripheral tissues.

RBC Formation and Turnover

• About 1% of circulating RBCs are replaced daily, with approximately 3 million new RBCs entering the bloodstream each second.
• Erythropoiesis occurs in embryos when embryonic blood cells move from the bloodstream to the liver, spleen, thymus, and bone marrow where they differentiate into stem cells that divide to produce blood cells.
• In adults, erythropoiesis occurs only in myeloid tissue (red bone marrow).
• Hemocytoblasts (hematopoietic stem cells or HSCs) in myeloid tissue divide to produce myeloid stem cells (become RBCs and some WBCs) and lymphoid stem cells that become lymphocytes.
• Hematologists have identified several stages of RBC maturation, starting with myeloid stem cells, then proerythroblasts, erythroblast stages, reticulocytes, and finally, mature RBCs.
• Erythropoietin (EPO) hormone stimulates erythropoiesis and is secreted by kidneys and liver when oxygen in peripheral tissues is low (hypoxia).
• Blood doping (re-infusing packed RBCs to elevate hematocrit) is a dangerous practice.
• Erythropoiesis requires amino acids, iron, folic acid, and vitamins B12 and B6; lack of vitamin B12 leads to pernicious anemia.

Hemoglobin Recycling

• Macrophages in the spleen, liver, and red bone marrow engulf aged RBCs and remove Hb molecules from hemolyzed RBCs where the Hb is broken into component molecules.
• Only the iron of each heme unit is recycled
• Hemoglobinuria: the presence of red or brown urine due to abnormally high hemolysis in bloodstream

Recycling cont.

• Hematuria: the presence of whole RBCs in urine due to kidney or blood vessel damage
• Iron removed from each heme unit forms green biliverdin then converts to orange-yellow bilirubin and is excreted by the liver in bile.
• Jaundice is caused by a buildup of bilirubin.
• Intestinal bacteria converts bilirubin to urobilins and stercobilins (urobilins make urine yellow, stercobilins make feces brown).
• Iron is removed from heme, is bound/ stored in phagocytic cells or released into the bloodstream
• In bloodstream, iron is bound to transferrin, which developing RBCs in red bone marrow absorb to synthesize Hb
• Excess transferrins are removed in the liver and spleen, storing iron in ferritin and hemosiderin

Blood Groups

• ABO and Rh are based on antigen-antibody responses.
• Surface antigens are substances on plasma membranes that identify cells to the immune system; normal cells are ignored, while foreign cells are attacked.
• Blood type is determined by presence or absence of surface antigens A, B, and Rh (or D).
• Type A has surface antigen A, Type B has surface antigen B, Type AB has antigens A and B, and Type O has neither of these.
• Rh positive (Rh+) has the Rh surface antigen (e.g., Type O+), while Rh negative (Rh−) lacks it (e.g., Type O-).
• Agglutinogens are surface antigens on RBCs and are screened by the immune system.
• Agglutinins are antibodies in plasma that attack antigens on foreign RBCs, causing agglutination (clumping).

Blood Types and Agglutinins

• Type A blood has anti-B antibodies, Type B blood has anti-A antibodies, Type O blood has both anti-A and anti-B antibodies, and Type AB blood has neither.
• Only sensitized Rh− blood has anti-Rh antibodies.
• Cross-reaction (transfusion reaction) occurs when donor and recipient blood types are NOT compatible.
• Plasma antibodies interact with specific surface antigens, causing RBCs to agglutinate and hemolyze.
• Compatibility testing and cross-matching are performed in advance of transfusions to reveal cross-reactions between donor's RBCs and recipient's plasma.
• Type O- is the universal donor, while Type AB+ is the universal recipient.
• Despite universal compatibility, cross-reactions can still occur because at least 48 surface antigens exist besides A and B.

White Blood Cells (WBCs)

• Also called leukocytes that contribute to the body's defense.
• They have nuclei, other organelles, and no hemoglobin.
• WBCs defend the body against pathogens, remove toxins and wastes, and attack abnormal or damaged cells.
• Most WBCs are 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 the bloodstream and are capable of amoeboid movement
• Undergo positive chemotaxis where all are attracted to specific chemical stimuli, and some are phagocytic

Types of WBCs

• Neutrophils, Eosinophils, Basophils (all granulocytes), Monocytes and Lymphocytes (agranulocytes).

Granulocytes

• Neutrophils (neutral pH stain), also called polymorphonuclear leukocytes, make up 50-70% of circulating WBCs.
• Pale cytoplasmic granules containing lysosomal enzymes and bactericidal compounds.
• Very active, phagocytic cells that attack and digest bacteria.
• Degranulation occurs when vesicles containing pathogens fuse with lysosomes containing enzymes and defensins.
• Neutrophils release prostaglandins and leukotrienes and live in the bloodstream for 10 hours or less; dead neutrophils contribute to pus.
• Eosinophils (acidic pH stains them reddish), also called acidophils, comprise 2-4% of circulating WBCs.
• Engulf bacteria, protozoa, cellulose, and cellular debris.
• Attack large parasites by releasing toxic compounds (nitric oxide and cytotoxic enzymes) and are sensitive to allergens.
• Release enzymes that reduce inflammation caused by mast cells and neutrophils.
• Basophils (basic pH stains them blue-blackish) make up less than 1% of circulating WBCs.
• Cross capillary endothelium and accumulate in damaged tissues, releasing histamine (dilates blood vessels) and heparin (prevents blood clotting).

Agranulocytes

• Monocytes are large, spherical cells that make up 2-8% of circulating WBCs, remain in the bloodstream for 24 hours

• They enter peripheral tissues to become macrophages, aggressive phagocytes that engulf large pathogens.

• They release chemicals that attract other phagocytic cells and fibroblasts to the injured area.

Lymphocytes

• Three classes of Lymphocytes
• T cells (T lymphocytes) are involved in cell-mediated immunity, attacking foreign cells or controlling other lymphocytes.
• B cells (B lymphocytes) handle humoral immunity, differentiating into plasma cells that synthesize antibodies.
• Natural killer (NK) cells can detect and destroy abnormal cells.

WBC

• Differential count of WBC population can detect infection, inflammation, and allergic reactions.
• Leukopenia: low WBC count
• Leukocytosis: high WBC count
• Leukemia: cancer of WBCs indicated by extreme leukocytosis
• Leukopoiesis: WBC production.

WBC Development

• Hemocytoblasts produce myeloid stem cells and lymphoid stem cells
• Myeloid stem cells divide to produce progenitor cells that give rise to all formed elements except lymphocytes.
• Lymphocytopoiesis is the production of lymphocytes from lymphoid stem cells.
• 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
• Thymus, spleen, and lymph nodes produce lymphocytes, and 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

• Disc-shaped cell fragments which are involved in clotting
• Circulate for 9-12 days, are removed by phagocytes mainly in the spleen.
• A microliter of blood should contain between 150,000 to 500,000 platelets.
• One-third of the body's platelets are stored in vascular organs like the spleen and mobilized during a circulatory crisis.

Function of Platelets

• Release important clotting chemicals.
• Temporarily patch damaged vessel walls
• Reduce the size of break in vessel walls
• Thrombocytopoiesis: platelet production, which occurs in red bone marrow.
• Megakaryocytes: giant cells in red bone marrow
• Produces platelets by shredding membrane-enclosed packets of cytoplasm

Hormonal Control of Platelet Production

• Thrombopoietin (TPO)
• Interleukin-6 (IL-6)
• Multi-CSF

Hemostasis

• Hemostasis or the process of blood clotting, stops blood loss. Hemostasis has three phases: vascular, platelet, and coagulation

Vascular Phase

• A cut triggers a vascular spasm, the contraction of smooth muscle fibers of the vessel wall that lasts 30 minutes
• Changes in the endothelium occur during the vascular phase
• Endothelial cells contract and expose the basement membrane to the bloodstream, releasing chemical factors and local hormones like ADP, tissue factor, and prostacyclin and endothelins (peptide hormones) that cause smooth muscle contraction and cell division.
• Endothelial plasma membranes become “sticky,” sealing off the tear and preventing blood flow.

Platelet Phase

• Platelet adhesion: the attachment of platelets to exposed surfaces
• Platelet aggregation: Platelets that stick to each other beginning 15 seconds after injury and forms platelet plug that closes small breaks.

Platelet Activation

• 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 Platelet Plus Growth

• Prostacyclin inhibits platelet aggregation, including inhibitory compounds released by WBCs
• Circulating enzymes break down ADP.
• Negative feedback from serotonin stops clotting.
• A blood clot isolates area from general circulation.

Coagulation Phase

• The coagulation phase (blood clotting) begins 30 seconds or more after injury depending on clotting factors (procoagulants Ca2+ and 11 different proteins) and proenzymes, inactive enzymes are converted to active enzymes that direct reactions in clotting response.
• Chain reactions in three pathways occurs in coagulation: extrinsic, intrinsic, and common pathway.
• The extrinsic pathway is where damaged endothelial cells or peripheral tissues release Factor III (tissue factor), and the enzyme complex activates Factor X.
• The intrinsic pathway begins with activation of proenzymes exposed to collagen fibers at the injury site, platelets release PF-3, and the enzyme complex activates Factor X.
• The common pathway begins with activation of Factor X, Factor X activates prothrombin activator, which converts prothrombin to thrombin, and thrombin converts fibrinogen to insoluble fibrin, producing blood clots.

Thrombin

• It stimulates release of tissue factor, stimulates the release of PF-3 by platelets and forms a positive feedback loop that accelerates clotting process.

Feedback Control of Blood Clotting

• Anticoagulants (enzymes that inhibit clotting) such as antithrombin-III 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 for all three pathways, all three of which require for synthesis of four clotting factors.

Bleeding and Clotting Extremes

• Thrombocytopenia
• Hemophilia
• Thrombophilia
• Deep vein thrombosis (DVT)
• Clot retraction pulls the torn edges of the vessel closer together which reduces residual bleeding.
• Stabilizing injury sites reduces the size of the damaged area, making it easier for fibroblasts, smooth muscle cells, and endothelial cells to complete repairs.

Explore the roles and composition of blood. Understand the function of blood including plasma proteins, pH levels, and compensatory mechanisms following blood loss. Learn about the differences between blood plasma and interstitial fluid.