Chapter 19! Blood! SECTION 19-1! Blood has several important functions and unique characteristics! 2! Functions of Blood - 1! 1. Transportation of:! Dissolved gases! Nutrients! Hormones! Metabolic wastes! Heat! 2. Regulation of ph and ion composition of ECF! Contains buffers! Diffusion between blood and ECF eliminates ion differences between them! 3! 1!
Functions of Blood - 2! 3. Restricts fluid loss at injury sites! Hemostasis - clotting! 4. Defense against toxins, pathogens! White blood cells! Antibodies! 5. Body temperature regulation! Redistributes heat! Facilitates heat loss or heat gain! 4! Composition of Whole Blood! 1. Plasma = fluid fraction! 2. Formed elements! Red blood cells (erythrocytes)! White blood cells (leukocytes)! Platelets (thrombocytes)! Hemo- or hematopoiesis = blood cell formation! Hemocytoblasts myeloid stem cells + lymphoid stem cells! Lymphoid stem cells lymphocytes! Myeloid stem cells other formed elements! 5! Characteristics of Normal Whole Blood! 1. Temperature about 38 C! 2. Viscosity = stickiness, cohesiveness! 5 times more viscous than water! viscosity harder for heart to pump! 3. ph: 7.35 7.45! 4. Blood volume! Estimate as 7 8% of body weight (in kg)! Adult male: 5 6 liters! Adult female: 4 5 liters! 6! 2!
The Composition of Whole Blood Spotlight 19-1! 7! SECTION 19-2! Plasma, the fluid portion of blood, contains significant quantities of plasma proteins! 8! Plasma Proteins 1! 1. Albumins! 60% of plasma proteins! Major source of blood colloid osmotic pressure! Transport lipid-soluble substances! 2. Globulins! Fatty acids, thyroid hormones, etc.! 35% of plasma proteins! A. Antibodies (immunoglobulins)! 9! 3!
Plasma Proteins 2! B. Transport globulins! Thyroid-binding globulin, transthyretin; transcortin (ACTH); transcalciferin (calcitriol)! Metalloproteins! e.g. Transferrin (Fe 2+ )! Apolipoproteins (triglycerides, other lipids)! Lipid + apolipoprotein = lipoprotein! e.g. HDL, LDL! Steroid-binding proteins! e.g. testosterone-binding protein! 10! Plasma Proteins 3! 3. Fibrinogen! 4% of plasma proteins! Circulates in blood in dissolved form! Fibrinogen fibrin clot! 4. Others! Plasma with clotting proteins removed is called serum! Peptide hormones (e.g. insulin)! Glycoprotein hormones (e.g. TSH, FSH, LH)! 11! Sources of Plasma Proteins! Liver (90%)! All albumins! Fibrinogen! Many globulins! Plasma cells! Antibodies (globulins)! Endocrine glands! Protein/peptide/glycoprotein hormones! 12! 4!
!! Composition of Plasma! Composition:! A. About 92% water! B. About 7% plasma proteins! Much higher [protein] than ECF! About 5 times higher - Why?! C. About 1% other solutes! Electrolytes, organic nutrients/wastes, etc.! 13! SECTION 19-3! Red blood cells, formed by erythropoiesis, contain hemoglobin that can be recycled! 14! Formed Elements in Blood Spotlight 19-1! 15! 5!
! Red Blood Cells! A.K.A. erythrocytes, red blood corpuscles! Contain hemoglobin - carries O 2 and CO 2! 99.9% of formed elements are RBCs! Hematocrit = % of whole blood that is cells! A.K.A. packed cell volume (PCV)! Average male: 46%! (Androgens stimulate erythropoiesis)! Average female: 42%! 16! The Anatomy of Red Blood Cells Figure 19-2! 17! RBC Structure! Biconcave disc! About 8 µm in diameter! No nucleus or most other organelles when mature! Retain cytoskeleton! No nucleus: no instructions for making repairs, cannot divide limited lifespan! Last about 120 days! No mitochondria! Why does this make sense?! About 3 million new RBCs produced per second in red marrow! 18! 6!
Advantages of Biconcave Shape! 1. Large surface area to volume ratio! Increased diffusional exchange across membrane! 2. Facilitates flow through narrow vessels! Form stacks of RBCs! 3. Allows bending and flexing of membrane! Can flow through 4 µm diameter vessels! 19! The Structure of Hemoglobin Figure 19-3! 20! Hemoglobin (Hb)! Normal values: male: 14 18 g/dl (a.k.a. g%)! female: 12 16 g/dl! Hb Structure:! 4 polypeptides and 4 heme groups! Heme = iron-containing pigment! O 2 reversibly binds to iron in heme! In adults:! 2 α and 2 β chains (4 polypeptides, 4 hemes)! Each Hb molecule can therefore carry 4 O 2! Oxyhemoglobin abbreviation = HbO 2! 21! 7!
Hb Recycling! Worn out RBCs (containing Hb and iron) are phagocytized by cells in:! Spleen! Liver! Bone marrow! Macrophages split heme from globin! A. Globin amino acids (recycled)! B. Heme group! Iron-containing portion! Non-iron containing portion! 22! Fate of Iron-containing Portion of Heme! 1. Iron released from macrophage! 2. Combines with plasma protein, transferrin! 3. Can be stored attached to ferritin and hemosiderin in:! Muscle and liver cells, and macrophages in spleen and liver! 4. New iron from gut or iron released from storage transported to bone marrow (by transferrin)! 5. Taken up via receptor-mediated endocytosis by RBC precursors (What do you know about this type of transport?)! 23! Fate of Non-iron Portion of Heme! 1. Macrophage: heme biliverdin (green) bilirubin (yellow-orange) released into blood! 2. Liver: bilirubin excreted in bile! 3. Bile enters small, then large intestine! 4. In large intestine: Bile urobilinogen! Urobilinogen in large intestine! Bacterial action: urobilinogen stercobilin (brown) feces! Urobilinogen blood kidney! Urobilinogen urobilin (yellow) urine! 24! 8!
Red Blood Cell Turnover Figure 19-4! 25! Stages of RBC Maturation Figure 19-5! Hemocytoblast! Myeloid stem cell!! Begin Hb synthesis! All are erythroblasts! Reticulocytes:! < 1% of circulating RBCs! Mature after about a day in blood! 26! Regulation of Erythropoiesis! RBC formation requires:! Amino acids (for globin)! Iron (for heme)! Vitamins (B 12, B 6, folic acid normal stem cell division)! Intrinsic factor from stomach (absorption of B 12 from diet)! Erythropoietin (EPO) from kidney stimulates production! 27! 9!
Stimulus for RBC Production! Stimulus = hypoxia = low tissue O 2 (in this case)! Causes erythropoietin (EPO) release from kidneys! Causes of tissue hypoxia! Anemia! Decreased hematocrit or [Hb]! Low blood flow to kidneys! Decreased O 2 content of air (e.g. high altitude)! Lung damage! 28! Effects of Erythropoietin (EPO)! 1. Stimulate mitosis in stem cells and erythroblasts! 2. Increased maturation and Hb synthesis rate! 3. Can increase RBC production up to 30 million/ sec!!!! 29! Blood Types! Antigen = a substance that triggers an immune response! Antibody = globular protein that binds antigen! RBC membranes may have glycolipid or glycoprotein surface antigens (agglutinogens)! Plasma may contain antibodies (agglutinins)! Binding of antibodies to antigens causes:! Agglutination (clumping)! Downstream tissue dies - and/or -! Hemolysis (rupture of RBCs)! Vasoconstriction, shock, kidney damage! 30! 10!
Blood Typing Figure 19-6! 31! ABO Blood Groups! Type Genotype(s) RBC antigen(s) Plasma antibody (antibodies) O.K. Donor? A AA or AO A Anti-b You B BB or BO B Anti-a figure AB AB AB None this O OO None Anti-a and Anti-b out 32! Blood Transfusions - the Bottom Line! When figuring out if a particular transfusion will be theoretically successful (i.e., the recipient won t have a potentially lethal reaction), ask yourself:! Does the recipient s blood contain antibodies that can attack antigens on the donated red blood cells?! Very important!! Yes? - Very BAD L! No? - Probably O.K. J! 33! 11!
Transfusion Example 1! Assume Rh factor (later) is compatible! Recipient (large volume) Donor (small volume) Type RBC antigens Plasma antibodies A A Anti-b B B Anti-a Dashed arrow = minor reaction: Small pool of donor antibodies attacks recipient RBCs.! Solid arrow = Major bummer : Large pool of recipient antibodies attacks donor RBCs. Agglutination, hemolysis: recipient may die.! 34! Transfusion Example 2! Assume Rh factor (later) is compatible! Recipient (large volume) Donor (small volume) Type RBC antigens Plasma antibodies AB AB None A A Anti-b In theory, this would be O.K. because:! Large pool of recipient s plasma does not have antibodies to attack donated blood! Small amount of donor antibodies would be diluted in large pool of recipient s blood.! 35! Example 3 - Universal donor! Assume Rh factor (later) is compatible! Recipient (large volume) Donor (small volume) Type RBC antigens Plasma antibodies A A Anti-b O None Anti-a and Anti-b Type O blood has no surface antigens to be attacked (agglutinated, hemolyzed) by any recipient s antibodies.! Donor antibodies diluted in large pool of recipient s blood.! 36! 12!
! Rh Factor! Rh comes from Rhesus monkey in which this was first studied.! Also called D antigens! Person with Rh antigens on RBCs is Rh +! Person without Rh antigens on RBCs is Rh -! Major difference from ABO grouping:!! Rh - person who has never been exposed to Rh + blood does not have anti-rh antibodies 37! Importance of Rh Factor 1! 1. Rh - person receives Rh + proper ABO blood transfusion! First transfusion O.K. (mild or no reaction)! Recipient makes antibodies to Rh factor over time! Second transfusion now a potential problem! 38! Importance of Rh Factor 2! Pregnant female:! Rh - mother and Rh + fetus (father was Rh + )! 1. First pregnancy probably O.K.! During delivery, maternal and fetal blood may mix! Mother makes anti-rh antibodies! 2. Next pregnancy with Rh + fetus:! Maternal antibodies may cross placenta! IgG antibodies - only ones that can do this! Produce hemolytic disease of the newborn! a.k.a. erythroblastosis fetalis! 39! 13!
Rh Factors and Pregnancy Spotlight 19-8! First! pregnancy! 40! Rh Factors and Pregnancy Figure 19-8! Second! pregnancy! RhoGam:! Anti-Rh antibodies! Destroy fetal Rh + RBCs before mother s body makes antibodies against them! Generally given last trimester and after delivery! 41! SECTION 19-5! The various types of white blood cells contribute to the body s defenses! 42! 14!
! WBC Summary 1 Table 19-3! 43! WBC Summary 2 Table 19-3! 44! White Blood Cells (WBCs) Leukocytes! About 1% of formed elements! Circulate in blood for limited times! Migrate to connective tissues of body! Granulocytes:! Neutrophils, basophils, eosinophils! Agranulocytes:! Monocytes, lymphocytes! Much more on this subject in Chapter 22! 45! 15!
WBC Characteristics! 1. Amoeboid movement! Move along vessel walls, through tissues! 2. Emigration or diapedesis! Adhere to vessel wall (margination)! Squeeze between endothelial cells into tissues 3. Chemotaxis! Attracted to specific chemical signals! 4. Phagocytosis! Microphages = neutrophils, eosinophils! Macrophages = monocytes! 46! 1. Neutrophils! a.k.a. polymorphonuclear leukocytes! Normally most numerous WBC (50-70%)! Structure:! Neutrally-staining granules! (i.e. not pink or purple)! 10-12 µm diameter! Multi-lobed nucleus! (polymorphonuclear)! Functions:! First line of defense (Not a good answer on a lab test!)! 47! Neutrophil Functions! 1. Phagocytize pathogens:! Especially microbes marked by antibodies or complement proteins! 2. Destroy pathogens with:! Strong oxidants (e.g. H 2 O 2, O 2- )! Defensins - poke holes in bacterial membrane! Digestive enzymes (e.g. lysozyme)! 3. Release chemicals into ECF:! Prostaglandins (promote inflammation)! Leukotrienes (attract other WBCs)! 48! 16!
!! 2. Eosinophils! Normally 2 4% of WBCs! Structure:! Pink-staining granules (Eos = goddess of dawn)! 2 or 3 lobes to nucleus! 10 12 µm diameter! (Granules pink with H&E or! Wright s stain in lab)! 49! Eosinophil Functions! 1. Release compounds toxic to pathogens! e.g. nitric oxide! 2. Phagocytize antigen-antibody and complexes! 3. Combat some parasitic worms (e.g. with NO, e.g., trichinosis, ascariasis (roundworms))! 4. Release antihistamine! Inhibits inflammation response! 50! 3. Basophils! Normally rare: 0.5 1% of WBCs! Structure:! Purple-staining granules! Often obscure (purple) nucleus! 8 10 µm diameter! Function to intensify inflammation:! Release histamine - dilate small vessels, increase capillary wall permeability (edema)! Release heparin (anti-coagulant)! Release serotonin (constrict large vessels)! 51! 17!
4. Monocytes! Normally 2 8% of WBCs! Structure:! Agranular! LARGE cells (12 20 µm dia.)! (In lab, look for a cell 2 3X larger than a RBC)! Kidney-shaped nucleus! Cytoplasm glassy! Note size of monocyte! compared to RBC.! Note kidney-shaped! nucleus.! 52! Monocyte Functions! Migrate to tissues! Become wandering or fixed macrophages! Highly phagocytic! Act as antigen-presenting cells! Release chemotaxic chemicals! (Call other WBCs to site of battle)! 53! Lymphocytes! 20 30% of WBCs in blood! Structure:! No visible granules! Round or dented nucleus! 6 14 µm diameter! Migration pattern:! Blood tissues blood tissues, etc.! Most are in tissues and lymphatic organs at any one time! Note cytoplasm visible around purple-staining nucleus.! This easily distinguishes a lymphocyte from a basophil in lab. (At least on a test!)! 54! 18!
! Lymphocyte General Functions - 1! A. B cells! Humoral or antibody-mediated immunity! (What does humoral refer to?)! Mature in bone marrow! Migrate to lymph nodes! Differentiate into plasma cells Secrete antibodies! Label invader for destruction! Act as antigen-presenting cells! 55! Lymphocyte General Functions - 2! B. T cells! Cell-mediated immunity! Mature in thymus (that s the T )! Attack virus-infected and cancerous cells, transplanted tissues! Types of T cells:! Cytotoxic (Killer) T cells! Helper T cells! Suppressor T cells! 56! Lymphocyte General Functions - 3! C. Natural Killer (NK) cells! Perform immune surveillance! Recognize a variety of antigens that they can attack! (B and T cells are much more specific)! Kill microbes, cancerous cells! Chapter 22 will cover lymphocyte function in detail! 57! 19!
WBC Origins and Differentiation Figure 19-10! Note: the arrows indicate the big picture. 58! WBC Production and Differentiation! Know the big picture:! Hemocytoblasts myeloid and lymphoid stem cells! Lymphoid stem cells lymphocytes! Myeloid stem cells progenitor cells all others (including RBCs)! 59! Colony-stimulating Factors (CSFs)! Not well understood, but promote growth and differentiation! M-CSF: Stimulates Monocyte production! G-CSF: Stimulates Granulocyte production! Neutrophils, eosinophils, basophils! GM-CSF: Stimulates Granulocytes and Monocytes! Multi-CSF: Stimulates granulocytes, monocytes, platelets, RBCs! Released by T cells, monocyte/macrophages, endothelial cells, fibroblasts. 60! 20!
SECTION 19-6! Platelets, disc-shaped structures formed from megakaryocytes, function in the clotting process! 61! Platelets! a.k.a. thrombocytes (but not really cells in humans)! Structure:! Are fragments of megakaryocytes! Up to 3.5 µm in diameter! Stain purple in lab! Contain vesicles (not visible)! Production = thromobcytopoiesis! Megakaryocyte 4000 platelets! Note how small the platelet! is when compared to an RBC.! 62! Platelet General Functions! Live 9 12 days! About 1/3 of total stored in spleen! 1. Transport clotting chemicals! 2. Form platelet plug! Temporary patch! 3. Contract after clot has formed! Reduce size of damaged area! 4. Production stimulated by:! Thrombopoietin from kidney, Interleukin-6, Multi-CSF! 63! 21!
SECTION 19-7! Hemostasis involves vascular spasm, platelet plug formation, and blood coagulation! 64! Hemostasis! Hemostasis = stoppage of bleeding! Three phases:! 1. Vascular phase (vascular spasm)! 2. Platelet phase (platelet plug formation)! 3. Coagulation phase (blood clotting)! 65! 1. Vascular Phase - 1! A. Reflexive contraction of smooth muscle! Vessel diameter decreases, blood flow decreases, so blood loss decreases! Potential contractile stimuli:! Pain receptors! Substances from activated platelets! Substances released from damaged smooth muscle cells! 66! 22!
1. Vascular Phase - 2! B. Endothelial changes! Endothelial cells contract, expose basal lamina to blood! Endothelial cells release chemicals, hormones! e.g. ADP, Tissue Factor, endothelins! Endothelins:! Stimulate smooth muscle contraction! Stimulate endothelial cell division! Endothelial cell membranes become sticky! Walls of vessels may stick together! 67! 2. Platelet Phase (Platelet Plug Formation)! A. Platelet adhesion! Platelets adhere to sticky endothelium! B. Platelet aggregation platelet plug formation! C. New arrivals activated, secrete chemicals! ADP aggregation and secretion! Thromboxane A 2 and serotonin vasoconstriction! Clotting Factors! Platelet-derived growth factor vessel repair! Ca 2+ aggregation and clotting! 68! Vascular and Platelet Phases Figure 19-11! 69! 23!
! 3. Coagulation Phase (Blood Clotting)! Plasma contains clotting factors (procoagulants)! e.g. Ca 2+ and proteins (many are proenzymes)! Activation (damage) produces an enzyme cascade! Fibrinogen fibrin fibrin polymer blood clot! Coagulation phase involves:! An extrinsic pathway,! An intrinsic pathway and both stimulate the! Common pathway (Figure 19-11)! 70! A. Extrinsic Pathway! Faster response compared to intrinsic pathway! Endothelial cells or peripheral (extrinsic) tissues damaged! Tissue factor (TF or Factor III) released from tissue (i.e. from outside (extrinsic to) the blood vessels:! TF binds Ca 2+! Ultimately activates Factor X (ten, not ex )! Factor X activates common pathway! 71! Coagulation Phase Extrinsic Figure 19-11! Extrinsic pathway 72! 24!
B. Intrinsic Pathway (Slower than extrinsic)! Necessary factors are within vascular system! Activators are either:! a. In direct contact with blood (collagen) -OR -! b. Contained within the blood (platelets)! Endothelial cell damage results in:! a. Blood coming into contact with collagen fibers! Proenzymes in blood activated (Factor XII)! b. Rough endothelial surface damages platelets! Release chemicals (e.g. PF-3)! Common pathway activated via Factor X! 73! Coagulation Phase Figure 19-13! Intrinsic pathway 74! C. Common Pathway! Common link between extrinsic and intrinsic paths! Vessel damage both pathways activated! Factor X activates prothrombinase! Prothrombin thrombin! Fibrinogen (soluble) fibrin (insoluble)! Clot! Antithrombin inactivates clotting factors away from site of injury!! 75! 25!
Coagulation Phase Figure 19-13! Common pathway 76! Feedback Control of Clotting! Thrombin from common pathway stimulates both extrinsic (TF) and intrinsic (PF-3) pathways! Positive feedback loop (see next slide)! Calcium, Vitamin K required for proper clotting! All three pathways require Ca 2+! Vitamin K required for synthesis of clotting factors by liver! Clot retraction and fibrinolysis! Platelets contract retract clot! Clot dissolved by plasmin (from plasminogen released by tissues)! 77! Positive Feedback in Clotting! 78! 26!
! Some Interesting Stuff! Vitamin K required for the synthesis of several clotting factors.! Warfarin (Coumadin) is antagonistic to Vitamin K, prevents synthesis of these factors! First used as a rat poison! Heparin! Present in tissues. Physiological significance unknown, but! Helps antithrombin inactivate clotting factors (thrombin and Factor X)! 79! 27!