Blood

Composition of Blood Blood is the body’s only fluid tissue It is composed of liquid plasma and formed elements Formed elements include: Erythrocytes, or red blood cells (RBCs) Leukocytes, or white blood cells (WBCs) Platelets

Overview of Blood Circulation Blood leaves the heart via arteries that branch repeatedly until they become capillaries Oxygen (O2) and nutrients diffuse across capillary walls and enter tissues Carbon dioxide (CO2) and wastes move from tissues into the blood

Overview of Blood Circulation Oxygen-deficient blood leaves the capillaries and flows in veins to the heart This blood flows to the lungs where it releases CO2 and picks up O2 The oxygen-rich blood returns to the heart

The Human Body Respiratory system Circulatory system Digestive system Figure 7.1 Oxygen intake Elimination of carbon dioxide Food and water intake The Human Body Respiratory system O2 CO2 Nutrients, salt, water Water, salts, metabolic waste Circulatory system Digestive system Urinary system Metabolic waste Transport to and from all cells Elimination of food residues, metabolic wastes Elimination of excess water, salts, metabolic wastes

Regulation Body Temperature Body PH Fluid Balance

Physical Characteristics and Volume Blood is a sticky, opaque fluid with a metallic taste The pH of blood is 7.35–7.45 Temperature is 38°C, slightly higher than “normal” body temperature; warms the areas it passes through Blood accounts for approximately 8% of body weight Average volume of blood is 5–6 L for males, and 4–5 L for females

Components of Whole Blood Plasma (55% of whole blood) Buffy coat: leukocyctes and platelets (<1% of whole blood) Formed elements Erythrocytes (45% of whole blood) 1 Withdraw blood and place in tube 2 Centrifuge Hematocrit – the percentage of RBCs out of the total blood volume Figure 17.1

Components of Blood Plasma (makes up 55% of whole blood) Water Electrolytes Proteins (albumins, globulins, clotting proteins) Hormones Gases Nutrients and wastes Formed elements (makes up 45% of whole blood) RBCs WBCs Platelets

Blood Plasma Blood plasma contains over 100 solutes, including: Proteins – albumin, globulins, clotting proteins, and others Nonprotein nitrogenous substances – lactic acid, urea, creatinine Organic nutrients – glucose, carbohydrates, amino acids Electrolytes – sodium, potassium, calcium, chloride, bicarbonate Respiratory gases – oxygen and carbon dioxide

Maintaining Osmotic Pressure

Albumins Smallest/Most abundant blood protein Exerts greatest colloid pressure Transport ions, hormones, lipids

Globulins Alpha/Beta – bind and transport water-insoluble molecules and hormones, some metals, and ions Gamma – a.k.a. antibodies

Fibrinogen Type of clotting protein

Formed Elements Erythrocytes, leukocytes, and platelets make up the formed elements Only WBCs are complete cells RBCs have no nuclei or organelles, and platelets are just cell fragments Most formed elements survive in the bloodstream for only a few days Most blood cells do not divide but are renewed by cells in bone marrow

Hemopoiesis

Erythrocytes (RBCs) Biconcave discs, anucleate, essentially no organelles 97 % hemoglobin (Hb), a protein that functions in gas transport Contain the plasma membrane protein spectrin and other proteins that: Give erythrocytes their flexibility Allow them to change shape as necessary

Erythrocytes (RBCs) Figure 17.3

Erythrocyte Function Erythrocytes are dedicated to respiratory gas transport Hemoglobin reversibly binds with oxygen and most oxygen in the blood is bound to hemoglobin Each heme group bears an atom of iron, which can bind to one oxygen molecule Each hemoglobin molecule can transport four molecules of oxygen

Hematocrit & Hemoglobin Hematocrit: the percentage of whole blood that consists of red blood cells Men: 43–49% Women: 37–43% Hemoglobin measurement Men: 14–18 gm% Women: 12–14 gm% Low hematocrit or hemoglobin may indicate anemia High hematocrit may be response to high elevation (less O2 available in atmosphere) Very high hematocrit—risky because of increased blood viscosity

Production of Erythrocytes: Erythropoiesis A hemocytoblast is transformed into a committed cell called the proerythroblast Proerythroblasts develop into early erythroblasts The developmental pathway consists of three phases Phase 1 – ribosome synthesis in early erythroblasts Phase 2 – hemoglobin accumulation in late erythroblasts and normoblasts Phase 3 – ejection of the nucleus from normoblasts and formation of reticulocytes Reticulocytes then become mature erythrocytes

Production of Erythrocytes: Erythropoiesis Figure 17.5

Role of EPO

Fate and Destruction of Erythrocytes The life span of an erythrocyte is 100–120 days Old erythrocytes become rigid and fragile, and their hemoglobin begins to degenerate Dying erythrocytes are engulfed by macrophages Heme and globin are separated and the iron is salvaged for reuse

Fate and Destruction of Erythrocytes Iron is transported by transferrin to liver and spleen Stored there until it’s return to the bone marrow for recycling Iron storage proteins: ferritin an hemosiderin

Fate and Destruction of Erythrocytes Heme is degraded to a yellow pigment called bilirubin The liver secretes bilirubin into the intestines as bile The intestines metabolize it into urobilinogen This degraded pigment leaves the body in feces, in a pigment called stercobilin Globin is metabolized into amino acids and is released into the circulation Hb released into the blood is captured by haptoglobin and phagocytized

Leukocytes (WBCs) Leukocytes, the only blood components that are complete cells: Are less numerous than RBCs Make up 1% of the total blood volume Can leave capillaries via diapedesis Move through tissue spaces Leukocytosis – WBC count over 11,000 per cubic millimeter Normal response to bacterial or viral invasion

Types of Leukocytes Granulocytes Agranulocytes Granules in the cytoplasm Agranulocytes Lack visible cytoplasmic granules

Leukocytes Found within body tissues as well as blood Diapedesis: movement of leukocytes from blood vessels to tissue

Leukocytes

Basophils Account for 0.5% of WBCs and: Have large, purplish-black (basophilic) granules that contain histamine Histamine – inflammatory chemical that acts as a vasodilator and attracts other WBCs (antihistamines counter this effect) Heparin - inhibits blood clotting

Eosinophils Eosinophils account for 1–4% of WBCs Lead the body’s counterattack against parasitic worms Lessen the severity of allergies by phagocytizing immune complexes

Neutrophils 60% of leukocytes First on the scene to fight an infection Phagocytize pathogens, especially bacteria

Monocytes Monocytes account for 4–8% of leukocytes Macrophages: They are the largest leukocytes They leave the circulation, enter tissue, and differentiate into macrophages Macrophages: Are highly mobile and actively phagocytic

Lymphocytes Account for 25% or more of WBCs and: Are found mostly enmeshed in lymphoid tissue (some circulate in the blood) There are two types of lymphocytes: T cells and B cells T cells function in the immune response B cells give rise to plasma cells, which produce antibodies

Changes in Leukocyte Count Leukopenia vs Leukocytosis Allergic reactions/Parasitic reactions - inc. eosinophils Chronic inflammatory disorders/ TB - inc. monocytes

Platelets Platelets are fragments of megakaryocytes Platelets function in the clotting mechanism by forming a temporary plug that helps seal breaks in blood vessels

Thrombopoiesis The stem cell for platelets is the hemocytoblast The sequential developmental pathway is hemocytoblast, megakaryoblast, promegakaryocyte, megakaryocyte, and platelets Figure 17.12

Hemostasis: Stopping Blood Loss Three stages 1. Vascular spasm: constriction of blood vessels to reduce blood flow 2. Platelet plug formation: sealing of the ruptured blood vessel 3. Coagulation: formation of a blood clot Blood changes from a liquid to a gel Complex series of reactions involving at least 12 different clotting proteins in the plasma

Clotting Cascade Damage to blood vessels initiates the process Platelets release prothrombin activator Prothrombin activator converts prothrombin (plasma protein) to thrombin (active enzyme) Thrombin converts fibrinogen (soluble plasma protein) to fibrin (insoluble fibers) Mass of fibrin, platelets, trapped RBCs forms blood clot Clot contracts and tightens

STEP 1: Blood vessel spasm (vascular spasm) When vessel damage occurs . . . STEP 1: Blood vessel spasm (vascular spasm)

STEP 2: Platelet plug forms

STEP 3: Blood coagulation (clotting)

The final key step in blood clot formation is the conversion of fibrinogen into fibrin.

Coagulation Intrinsic pathway Extrinsic pathway Triggered by damage to inside of the vessel Takes 3-6 min Extrinsic pathway Caused by damage to outside the vessel Takes 15 seconds

Clot Retraction As clot forms, actinomyosin, contracts and squeezes the serum out of the developing clot Plasmin degrades the fibrin strands through fibrinolysis

Undesirable Clotting Thrombus Embolus A clot in an unbroken vessel Can be fatal in coronary vessels Embolus A thrombus that breaks away and floats in the blood stream Can clog vessels in other areas

Hemophilia Deficiency of one or more clotting factors Unable to form clots sufficiently Complications Life threatening hemorrhage Painful, swollen joints Infections Easy bruising

Blood Disorders Red blood cells Anemia: reduction in oxygen-carrying capacity due to inadequate number of red blood cells or inadequate hemoglobin Iron-deficiency anemia: caused by inadequate intake or malabsorption of dietary iron Hemorrhagic anemia: caused by blood loss Pernicious anemia: caused by Vitamin B12 deficiency Hemolytic anemia: caused by destruction of red blood cells Anemia due to renal failure Results from inadequate erythropoietin secretion

Sickle Cell Disease

Leukemia Excessive proliferation of leukocytes Cancer begins in bone marrow

Human Blood Groups RBC membranes have glycoprotein antigens on their external surfaces These antigens are: Unique to the individual Recognized as foreign if transfused into another individual Promoters of agglutination and are referred to as agglutinogens Presence or absence of these antigens is used to classify blood groups

ABO Blood Groups The ABO blood groups consists of: Two antigens (A and B) on the surface of the RBCs Two antibodies in the plasma (anti-A and anti-B) Agglutinogens and their corresponding antibodies cannot be mixed without serious hemolytic reactions

Rh Blood Groups Presence of the Rh agglutinogens on RBCs is indicated as Rh+ Anti-Rh antibodies are not spontaneously formed in Rh– individuals However, if an Rh– individual receives Rh+ blood, anti-Rh antibodies form A second exposure to Rh+ blood will result in a typical transfusion reaction

Antibody binds to antigen. Antibodies ignore Figure 7.11 “Self” surface protein Foreign cell Antigen-antibody complex Antigen Antibody Antibody binds to antigen. Antibodies ignore the “self” surface proteins but bind to the antigen of the foreign cell, forming an antigen-antibody complex. Antigen-antibody complexes clump together. Clumping effectively inactivates the foreign cells.

Type A Type B Type AB Type O Red blood cells Plasma antibodies Figure 7.12 Type A Type B Type AB Type O Antigen A Antigen B Antigens A and B Neither A nor B antigens Red blood cells Plasma antibodies B A Neither A nor B A and B Incidences: U.S. Caucasians U.S. African Americans Native Americans 40% 27% 8% 10% 20% 1% 5% 4% 0% 45% 49% 91%

Rh Blood Typing Is Based On the Rh Factor Rh factor: another antigen found on red blood cell surfaces 85% of Americans are Rh-positive (have the antigen) 15% are Rh-negative These individuals will respond to Rh-positive blood by producing anti-Rh antibodies

Rh Blood Typing Is Based On the Rh Factor Can be a problem when an Rh-negative women is pregnant with an Rh-positive fetus Mother may produce anti-Rh antibodies that cross placenta and damage fetal red blood cells Anti-Rh antibodies from mother cause hemolytic disease of the newborn Rh-positive baby Risk much higher for second and subsequent pregnancies Can be prevented by giving mother Rho-GAM (anti- Rh antibodies) during pregnancy and at delivery

being tested Antibodies Anti-A Anti-B Figure 7.14 Blood being tested Antibodies Anti-A Anti-B Type A (Contains antigen A) Type B (Contains antigen B) Agglutinated blood Type AB (Contains antigens A and B) Type O (Contains neither A nor B antigens)

Hemolytic Disease in Pregnancy https://www.youtube.com/watch?v=e2KK86bekNw