Blood, a more in-depth examination Section 1: Blood • Functions of blood – Transportation of dissolved gases, nutrients, hormones, and metabolic wastes – Regulation of the pH and ion composition of interstitial fluids – Restriction of fluid loss at injury sites – Defense against toxins and pathogens – Stabilization of body temperature Module 17.1: Blood components • Blood – Is a fluid connective tissue – About 5 liters (5.3 quarts) in body • 5–6 in males, 4–5 in females (difference mainly body size) – Consists of: • Plasma (liquid matrix) • Formed elements (cells and cell fragments) – Properties • Temp is roughly 38°C (100.4°F) • Is 5× more viscous than water (due to solid components) • Is slightly alkaline (average pH 7.4) Module 17.1: Blood components • Whole blood – Term for removed blood when composition is unaltered • May be fractionated or separated – Plasma » 46%–63% of blood volume – Hematocrit (or packed cell volume [PCV]) » Percentage of whole blood contributed by formed elements (99% of which are red blood cells) » Average 47% for male (range 40%–54%) » Average 42% for female (range 37%–47%) Module 17.1: Blood components • Plasma – Composition resembles interstitial fluid in many ways • • • • Exists because exchange of water, ions, and small solutes 92% water 7% plasma proteins 1% other solutes – Primary differences • Levels of respiratory gases (oxygen and carbon dioxide) • Concentrations of dissolved proteins (cannot cross capillary walls) Module 17.1: Blood components • Plasma proteins – In solution rather than as fibers like other connective tissues – Each 100 mL has ~7.6 g of protein • ~5× that of interstitial fluid – Large size and globular shapes prevent leaving bloodstream – Liver synthesizes >90% of all plasma proteins Module 17.1: Blood components • Plasma proteins (continued) – Albumins • ~60% of all plasma proteins • Major contributors to plasma osmotic pressure – Globulins • ~35% of all plasma proteins • Antibodies (immunoglobulins) that attack pathogens • Transport globulins that bind ions, hormones, compounds – Fibrinogen • Functions in clotting and activate to form fibrin strands – Many active and inactive enzymes and hormones Module 17.1: Blood components • Plasma solutes – Electrolytes • Essential for vital cellular activities • Major ions are Na+, K+, Ca2+, Mg2+, Cl–, HCO3–, HPO4–, SO42– – Organic nutrients • Used for cell ATP production, growth, and maintenance • Includes lipids, carbohydrates, and amino acids – Organic wastes • Carried to sites of breakdown or excretion • Examples: urea, uric acid, creatinine, bilirubin, NH4+ Plasma (46–63%) Whole blood consists of Formed elements (37–54%) Figure 17.1 1 Module 17.1: Blood components • Formed elements – Platelets • Small membrane-bound cell fragments involved in clotting – White blood cells (WBCs) • Also known as leukocytes (leukos, white + -cyte, cell) • Participate in body’s defense mechanisms • Five classes, each with different functions – Red blood cells (RBCs) • Also known as erythrocytes (erythros, red + -cyte, cell) • Essential for oxygen transport in blood Module 17.1 Review a. Define hematocrit. b. Identify the two components constituting whole blood, and list the composition of each. c. Which specific plasma proteins would you expect to be elevated during an infection? Module 17.2: Red blood cells • RBCs in blood – Most numerous cell type in blood • Roughly 1/3 of all cells in the body – Red blood cell count (standard blood test) results • • • Adult males: 4.5–6.3 million RBCs/1 µL or 1 mm3 of whole blood Adult females: 4.2–5.5 million RBCs/1 µL or 1 mm3 of whole blood One drop = 260 million RBCs Module 17.2: Red blood cells • RBC characteristics – Biconcave disc – Average diameter ~8 µm – Large surface area-to-volume ratio • Greater exchange rate of oxygen – Can form stacks (rouleaux) • Facilitate smooth transport through small vessels – Are flexible • Allow movement through capillaries with diameters smaller than RBC (as narrow as 4 µm) Stained blood smear LM x 450 Figure 17.2 1 The size and biconcave shape of an RBC 7.2–8.4 μm 0.45–1.16 μm RBCs 2.31–2.85 μm Colorized SEM x 1800 Figure 17.2 2 The advantages of the biconcave shape of RBCs Functional Aspects of Red Blood Cells • Large surface area-to-volume ration. Each RBC carries oxygen bound to intracellular proteins, and that oxygen must be absorbed or released quickly as the RBC passes through the capillaries. The greater the surface area per unit volume, the faster the exchange between the RBC’s interior and the surrounding plasma. The total surface area of all the RBCs in the blood of a typical adult is about 3800 square meters, roughly 2000 times the total surface area of the body. Rouleaux (stacks of RBCs) Blood vessels (viewed in longitudinal section) • RBCs can form stacks. Like dinner plates, RBCs can form stacks that ease the flow through narrow blood vessels. An entire stack can pass along a blood vessel only slightly larger than the diameter of a single RBC, whereas individual cells would bump the walls, bang together, and form logjams that could restrict or prevent blood flow. • Flexibility. Red blood cells are very flexible and can bend and flex when entering small capillaries and branches. By changing shape, individual RBCs can squeeze through capillaries as narrow as 4 μm. Nucleus of endothelial cell Red blood cell (RBC) Sectional view of capillaries LM x 1430 Figure 17.2 3 Module 17.2: Red blood cells • RBC characteristics (continued) – Lose most organelles including nucleus during development • – Cannot repair themselves and die in ~120 days Contain many molecules (hemoglobin) associated with primary function of carrying oxygen • • Each cell contains ~280 million hemoglobin (Hb) molecules Normal whole blood content (grams per deciliter) – • 14–18 dL (males), 12–16 dL (females) ~98.5% of blood oxygen attached to Hb in RBCs – Rest of oxygen dissolved in plasma Module 17.2: Red blood cells • Hemoglobin – – Protein with complex quaternary structure Each molecule has 4 chains (globular protein subunits) • • – 2 alpha (α) chains 2 beta (β) chains Each chain contains a single heme pigment molecule • Each heme (with iron) can reversibly bind one molecule of oxygen – Forms oxyhemoglobin (HbO2) (bright red) » Deoxyhemoglobin when not binding O2 (dark red) Figure 17.2 4 The quaternary structure of hemoglobin β chain 1 α chain 1 β chain 2 Heme α chain 2 Figure 17.2 5 The chemical structure of a heme unit Heme Figure 17.2 6 Module 17.2 Review a. Define rouleaux. b. Describe hemoglobin. c. Compare oxyhemoglobin with deoxyhemoglobin. Module 17.3: Red blood cell production and recycling • RBC production and recycling – Events occurring in red bone marrow • Blood cell formation (erythropoiesis) occurs only in red bone marrow (myeloid tissue) – Located in vertebrae, ribs, sternum, skull, scapulae, pelvis, and proximal limb bones • Fatty yellow bone marrow can convert to red bone marrow in cases of severe, sustained blood loss • Developing RBCs absorb amino acids and iron from bloodstream and synthesize Hb Module 17.3: Red blood cell production and recycling • Events occurring in red bone marrow (continued) – Stages • Proerythroblasts • Erythroblasts – Actively producing Hb – After four days becomes normoblast • Reticulocyte (80% of mature cell Hb) – Ejects organelles including nucleus – Enters bloodstream after two days – After 24 hours in circulation, is mature RBC Module 17.3: Red blood cell production and recycling • Events occurring at macrophages – Engulf old RBCs before they rupture (hemolyze) – Hemoglobin recycling • Iron – Stored in phagocyte – Released into bloodstream attached to plasma protein (transferrin) • Globular proteins disassembled into amino acids for other uses • Heme biliverdin bilirubin bloodstream • Hemoglobin not phagocytized breaks down into protein chains and eliminated in urine (hemoglobinuria) Module 17.3: Red blood cell production and recycling • Events occurring at liver – Bilirubin excreted into bile • Accumulating bile due to diseases or disorders can lead to yellowish discoloration of eyes and skin (jaundice) • Events occurring at the large intestine – Bacteria convert bilirubin to urobilins and stercobilins which become part of feces • Give feces yellow-brown or brown coloration Module 17.3: Red blood cell production and recycling • Events occurring at kidneys – Excrete some hemoglobin and urobilins • Give urine its yellow color – Presence of intact RBCs in urine (hematuria) • Only after urinary tract damage Events Occurring in the Red Bone Marrow Start Developing RBCs absorb amino acids and Fe2+ from the bloodstream and synthesize new Hb molecules. Proerythroblasts then differentiate into various stages of cells called erythroblasts, which actively synthesize hemoglobin. Erythroblasts are named according to total size, amount of hemoglobin present, and size and appearance of the nucleus. Events in the life cycle of RBCs Events Occurring in Macrophages Macrophages in liver, spleen, and bone marrow Fe2+ Heme Fe2+ transported in circulation RBC formation by transferrin Amino acids Average life span of RBC is 120 days 90% Biliverdin Bilirubin 10% Bilirubin bound to albumin in bloodstream Cells destines to become RBCs first differentiate into proerythroblasts. Old and damaged RBCs In the bloodstream, the rupture of RBCs is called hemolysis. Hemoglobin that is not phagocytized breaks down, and the alpha and beta chains are eliminated in urine. When abnormally large numbers of RBCs break down in the bloodstream, urine may turn red or brown. This condition is called hemoglobobinuria. Ejection of nucleus After roughly four days of differentiation, the erythroblast, now called a normoblast, sheds its nucleus and becomes a reticulocyte (re-TIK-ū-lō-sīt), which contains 80 percent of the Hb of mature RBC. After two days in the bone marrow, reticulocytes enter the bloodstream. After 24 hours in circulation, the reticulocytes complete their maturation and become indistinguishable from other mature RBCs. New RBCs released into circulation Liver Bilirubin Events Occurring in the Kidney Absorbed into the circulation Excreted in bile Hb Events Occurring in the Liver Bilirubin Urobilins Urobilins, sterconilins Events Occurring in the Large Intestine Eliminated in feces Eliminated in urine Figure 17.3 Module 17.3 Review a. Define hemolysis. b. Identify the products formed during the breakdown of heme. c. In what way would a liver disease affect the level of bilirubin in the blood? Module 17.4: Blood types • Blood types – Determined by presence or absence of cell surface markers (antigens) • • • • Are genetically determined glycoproteins or glycolipids Can trigger a protective defense mechanism (immune response) Identify blood cells as “self” or “foreign” to immune system More than 50 blood cell surface antigens exist – Three particularly important » A, B, Rh (or D) Module 17.4: Blood types • Four blood types (AB antigens) 1. Type A (A surface antigens) • Anti-B antibodies in plasma 2. Type B (B surface antigens) • Anti-A antibodies in plasma 3. Type AB (Both A and B surface antigens) • No anti-A or anti-B antibodies in plasma 4. Type O (no A or B surface antigens) • Both anti-A and anti-B antibodies in plasma The characteristics of blood for each of the four blood types Type A Type B Type A blood has RBCs with surface antigen A only. Type B blood has RBCs with surface antigen B only. Surface antigen A Surface antigen B If you have Type A blood, your plasma contains anti-B antibodies, which will attack Type B surface antigens. If you have Type B blood, your plasma contains anti-A antibodies. Type AB Type O Type AB blood has RBCs with both A and B surface antigens. Type O blood has RBCs lacking both A and B surface antigens. If you have Type AB blood, your plasma has neither anti-A nor anti-B antibodies. If you have Type O blood, your plasma contains both anti-A and anti-B antibodies. Figure 17.4 1 Module 17.4: Blood types • Rh surface antigens – Separate antigen from A or B – Presence or absence on RBC determines positive or negative blood type respectively – Examples: AB+, O– Figure 17.4 3 Module 17.4: Blood types • Antigen-antibody interactions – Antibodies “protect our bodies” from “foreign” blood cells • – Anti-A and anti-B antibodies remain constant through life while antiRh antibodies can develop for Rh– people If one blood type is exposed to corresponding antibodies, clumping (agglutination) occurs • • Hemolysis may occur Cross-reactions (transfusion reactions) can block blood vessels to vital organs with agglutinated RBCs or cell fragments – Important to make sure donor and recipient blood types are compatible (will not cross-react) The events in a cross-reaction between incompatible donor and recipient blood types RBC Surface antigens Opposing antibodies Agglutination (clumping) Hemolysis Figure 17.4 2 Results of blood typing tests on blood samples from four individuals Anti-A Anti-B Anti-D Blood type A+ B+ AB+ O– Figure 17.4 4 Module 17.4 Review a. What is the function of surface antigens on RBCs? b. Which blood type(s) can be safely transfused into a person with Type O blood? c. Why can’t a person with Type A blood safely receive blood from a person with Type B blood? CLINICAL MODULE 17.5: Newborn hemolytic disease • Newborn hemolytic disease – Genetically determined antigens mean that a child can have a blood type different from either parent – During pregnancy, the placenta restricts direct transport between maternal and infant blood • • Anti-A and anti-B antibodies are too large to cross Anti-Rh antibodies can cross – Can lead to mother’s antibodies attacking fetal RBCs CLINICAL MODULE 17.5: Newborn hemolytic disease • First pregnancy with Rh– mother and Rh+ infant – During pregnancy, few issues occur because no anti-Rh antibodies exist in maternal circulation – During birth, hemorraging may expose maternal blood to fetal Rh+ cells • Leads to sensitization or activation of mother’s immune system to produce anti-Rh antibodies Rh– mother First Pregnancy of an Rh– Mother with an Rh+ infant Rh+ fetus The most common form of hemolytic disease of the newborn develops after an Rh– women has carried an Rh+ fetus. During First Pregnancy Problems seldom develop during a first pregnancy, because very few fetal cells enter the maternal circulation then, and thus the mother’s immune system is not stimulated to produce anti-Rh antibodies. Maternal blood supply and tissue Placenta Fetal blood supply and tissue Exposure to fetal red blood cell antigens generally occurs during delivery, when bleeding takes place at the placenta and uterus. Such mixing of fetal and maternal blood can stimulate the mother’s immune system to produce anti-Rh antibodies, leading to sensitization. Hemorrhaging at Delivery Maternal blood supply and tissue Fetal blood supply and tissue Roughly 20 percent of Rh– mothers who carried Rh+ children become sensitized within 6 months of delivery. Because the anti-Rh antibodies are not produced in significant amounts until after delivery, a woman’s first infant is not affected. Rh antigen on fetal red blood cells Maternal Antibody Production Maternal blood supply and tissue Maternal antibodies to Rh antigen Figure 17.5 • CLINICAL MODULE 17.5: Newborn hemolytic disease Second pregnancy with Rh– mother and Rh+ infant – Subsequent pregnancy with Rh+ infant can allow maternal anti-Rh antibodies to cross placental barrier • Attack fetal RBCs and cause hemolysis and anemia – – = Erythroblastosis fetalis Full transfusion of fetal blood may be necessary to remove maternal anti-Rh antibodies Prevention – • RhoGAM antibodies can be administered to maternal circulation at 26– 28 weeks and before/after birth – – Destroys any fetal RBCs that cross placenta Prevents maternal sensitization Rh– mother Second Pregnancy of an Rh– Mother with an Rh+ Infant If a subsequent pregnancy involves an Rh+ fetus, maternal anti-Rh antibodies produced after the first delivery cross the placenta and enter the fetal bloodstream. These antibodies destroy fetal RBCs, producing a dangerous anemia. The fetal demand for blood cells increases, and they begin leaving the bone marrow and entering the bloodstream before completing their development. Because these immature RBCs are erythroblasts, HDN is also known as erythroblastosis fetalis. Fortunately, the mother’s anti-Rh antibody production can be prevented if such antibodies (available under the name RhoGAM) are administered to the mother in weeks 26–28 of pregnancy and during and after delivery. These antibodies destroy any fetal RBCs that cross the placenta before they can stimulate a maternal immune response. Because maternal sensitization does not occur, no anti-Rh antibodies are produced. Rh+ fetus During Second Pregnancy Maternal blood supply and tissue Maternal anti-Rh antibodies Fetal blood supply and tissue Hemolysis of fetal RBCs Figure 17.5 CLINICAL MODULE 17.5 Review a. Define hemolytic disease of the newborn (HDN). b. Why is RhoGAM administered to Rh– mothers? c. Does an Rh+ mother carrying an Rh– fetus require a RhoGAM injection? Explain your answer. Module 17.6: White blood cells • White blood cells (leukocytes) – Spend only a short time in circulation • Mostly located in loose and dense connective tissues where infections often occur • Can migrate out of bloodstream – Contact and adhere to vessel walls near infection site – Squeeze between adjacent endothelial cells – = Emigration or diapedesis • Are attracted to chemicals from pathogens, damaged tissues, or other WBCs – = Positive chemotaxis Module 17.6: White blood cells • White blood cell types 1. Granular leukocytes (have cytoplasmic granules) • • • Neutrophil Eosinophil Basophil 2. Agranular leukocytes (lacking cytoplasmic granules) • • Monocyte Lymphocyte • Changing populations of different WBC types associated with different conditions can be seen in a differential WBC count Module 17.6: White blood cells • Granular leukocytes – Neutrophils • Multilobed nucleus • Phagocytic cells that engulf pathogens and debris – Eosinophils • Granules generally stain bright red • Phagocytic cells that engulf antibody-labeled materials – Increase abundance with allergies and parasitic infections – Basophils • Granules generally stain blue • Release histamine and other chemicals promoting inflammation The structure and function of white blood cells (leukocytes) GRANULAR LEUKOCYTES Neutrophil Eosinophil Basophil WBCs can be divided into two classes Shared Properties of WBCs • WBCs circulate for only a short portion of their life span, using the bloodstream primarily to travel between organs and to rapidly reach areas of infection or injury. White blood cells spend most of their time migrating through loose and dense connective tissues throughout the body. AGRANULAR LEUKOCYTES Monocyte Lymphocyte • All WBCs can migrate out of the bloodstream. When circulating white blood cells in the bloodstream become activated, they contact and adhere to the vessel walls and squeeze between adjacent endothelial cells to enter the surrounding tissue. This process is called emigration, or diapedesis (dia, through; pedesis, a leaping). • All WBCs are attracted to specific chemical stimuli. This characteristic, called postive chemotaxis (kē-mō-TAK-sis), guides WBCs to invading pathogens, damaged tissues, and other active WBCs. • Neutrophils, eosinophils, and monocytes are capable of phagocytosis. These phagocytes can engulf pathogens, cell debris, or other materials. Macrophages are monocytes that have moved out of the bloodstream and have become actively phagocytic. Figure 17.6 Module 17.6: White blood cells • Agranular leukocytes – Monocytes • Large cells with bean-shaped nucleus • Enter tissues and become macrophages (phagocytes) – Lymphocytes • Slightly larger than RBC with large round nucleus • Provide defense against specific pathogens or toxins Module 17.6 Review a. Identify the five types of white blood cells. b. Which type of white blood cell would you find in the greatest numbers in an infected cut? c. How do basophils respond during inflammation? Module 17.7: Formed element production • Formed elements – Appropriate term since platelets are cell fragments • Platelets – – – Structure: flattened discs that appear round when viewed from top but spindle-shaped in blood smear Function: clump together and stick to damaged vessel walls where they release clotting chemicals Immediate precursor cell is megakaryocyte (mega-, big + karyon, nucleus + -cyte, cell) Figure 17.7 2 • Module 17.7: Formed element production Formed element production – – All formed elements are produced in adult red bone marrow All cells arise from multipotent stem cells • • = Hemocytoblasts (hemo-, blood + cyto, + blastos, precursor) Give rise to two other stem cell lines 1. 2. Lymphoid stem cells (produce lymphocytes) » Occur in red marrow and lymphoid tissues Myeloid stem cells (produce other formed elements) Animation: Formed Elements The early stages in the development of formed elements, which occurs in the highly vascular red marrow of adult bones Figure 17.7 1 The early stages in the development of formed elements, which occurs in the highly vascular red marrow of adult bones Nutrient artery Venous sinuses Red bone marrow Figure 17.7 1 The early stages in the development of formed elements, which occurs in the highly vascular red marrow of adult bones Lymphoid Stem Cells Hemocytoblasts Hemocytoblasts (hemo-, blood + cyte, cell + blastos, precursor), or multipotent stem cells, are found in the red bone marrow of adults. Their divisions give rise to two types of stem cells responsible for producing all formed elements. Lymphoid stem cells, which are responsible for the production of lymphocytes, originate in the red bone marrow. Some remain there, while others migrate from the bone marrow to other lymphoid tissues, including the thymus, spleen, and lymph nodes. As a result, lymphocytes are produced in these organs as well as in the red bone marrow. Myeloid Stem Cells Myeloid Stem Cells are stem cells in red bone marrow that divide to give rise to all types of formed elements other than lymphocytes. Figure 17.7 1 Module 17.7: Formed element production • Erythropoietin (EPO) – Released into plasma when peripheral tissues (especially kidneys) have low oxygen (hypoxia) • Examples 1. 2. 3. 4. During anemia When kidney blood flow declines When oxygen content of air in lungs declines due to disease or altitude When respiratory surfaces are damaged – Transported to red bone marrow and stimulates stem cells and developing RBCs Module 17.7 Review a. Define hemocytoblast. b. Explain the role of erythropoietin. c. Compare lymphoid stem cells with myeloid stem cells. Module 17.8: Hemostasis • Hemostasis (haima, blood + stasis, halt) – Stops blood loss from damaged blood vessel walls – Establishes framework for tissue repairs – Usually divided into three phases but continuous process 1. Vascular phase 2. Platelet phase 3. Coagulation phase Module 17.8: Hemostasis 1. Events of the vascular phase – Endothelial cells contract exposing underlying basal lamina to bloodstream Endothelial cells release chemical factors, local hormones, and endothelins – • Endothelin functions 1. 2. – Stimulate smooth muscle and vascular spasms Stimulate division of endothelial cells, smooth muscle cells, and fibroblasts Endothelial cells become sticky • • In capillaries, cells can reduce flow in vessel Can cause platelets to attach The vascular phase of hemostasis Vascular Phase Lasts for roughly 30 minutes after the injury occurs; is dominated by the response of the endothelial cells and the smooth muscle of vessel walls Knife blade Blood vessel injury Vascular spasm Events of the Vascular Phase • The endothelial cells contract and expose the underlying basal lamina to the bloodstream. • The endothelial cells begin releasing chemical factors and local hormones. Endothelial cells also release endothelins, peptide hormones that (1) stimulate smooth muscle contraction and promote vascular spasms and (2) stimulate the division of endothelial cells, smooth muscle cells, and fibroblasts to accelerate the repair process. • The endothelial plasma membranes become “sticky”. A tear in the wall of a small artery or vein may be partially sealed off by the attachment of endothelial cells on either side of the break. In small capillaries, endothelial cells on opposite sides of the vessel may stick together and prevent blood flow along the damaged vessel. The stickiness also facilitates the attachment of platelets as the platelet phase gets under way. Figure 17.8 1 Module 17.8: Hemostasis 2. Events of the platelet phase – Begins with platelet attachment to endothelial cells, basal lamina, exposed collagen fibers, and each other Platelets release chemicals – • • • • • ADP (stimulates platelet aggregation and secretion) Chemicals that stimulate vascular spasm Platelet factors (proteins play role in clotting) Platelet-derived growth factor (PDGF) (promotes vessel repair) Calcium ions (required for platelet aggregation and clotting process) The platelet phase of hemostasis Platelet Phase Begins with the attachment of platelets to sticky endothelial surfaces, to the basal lamina, to exposed collagen fibers, and to each other Plasma in vessel lumen Release of chemicals (ADP, PDGF, Ca2+, platelet factors) Platelet aggregation Endothelium Platelet adhesion to damaged vessel Basal lamina Vessel wall Platelet plug may form Interstitial fluid Contracted smooth muscle cells Cut edge of vessel wall Chemicals Released by Activated Platelets • Adenosine diphosphate (ADP), which stimulates platelet aggregation and secretion • Several chemicals that stimulate vascular spasms • Platelet factors, proteins that play a role in blood clotting • Platelet-derived growth factor (PDGF), a peptide that promotes vessel repair • Calcium ions, which are required for platelet aggregation and in several steps in the clotting process Figure 17.8 2 Module 17.8: Hemostasis 3. Events of coagulation phase • • Starts 30 seconds or more after damage Involves complex sequence of steps leading to conversion of circulating fibrinogen to insoluble fibrin – • Procoagulants (clotting factors) play a key role – – • Blood cells and platelets are trapped in fibrin network Many are enzymes essential to clotting response Activated enzymes lead to chain reaction (cascade) Two pathways that both lead to common pathway – Extrinsic and Intrinsic Module 17.8: Hemostasis 3. Events of coagulation phase (continued) • Extrinsic pathway – – Begins with release of tissue factor (Factor III) from endothelial cells or peripheral tissues Tissue factor combines with Ca2+ and another clotting factor to activate Factor X (first step in common pathway) Module 17.8: Hemostasis 3. Events of coagulation phase (continued) • Intrinsic pathway – – – Begins with proenzymes exposed to collagen fibers at injury site Pathway proceeds with assistance of PF-3 (factor released by aggregating platelets) Sequence of enzyme activations leads to Factor X Module 17.8: Hemostasis 3. Events of coagulation phase (continued) • Common Pathway – – Activated Factor X forms prothrombinase » An enzyme that converts proenzyme prothrombin to the enzyme thrombin Thrombin converts fibrinogen to fibrin » Completes clotting process • Clot retraction – RBCs and platelets stick to clot • Platelets contract to form tighter clot Module 17.8: Hemostasis • Events of dissolving clots (fibrinolysis) after tissue repair – Proenzyme plasminogen is activated by • • Thrombin in common pathway Tissue plasminogen activator (t-PA) released by damaged tissues – Plasminogen becomes plasmin which erodes clot Module 17.8 Review a. Define hemostasis. b. Briefly describe the vascular, platelet, and coagulation phases of hemostasis. c. Provide the correct sequence for the following list of events involved in the process of hemostasis: 1. coagulation; 2. fibrinolysis; 3. vascular spasm; 4. retraction; 5. platelet phase. CLINICAL MODULE 17.9: Blood disorders and diseases • Blood disorders and diseases – Venipuncture (vena, vein + punctura, a piercing) • • Withdrawal of whole blood from vein Commonly used because: 1. Easy to locate superficial veins 2. Vein walls are thinner than comparable arteries 3. Venous blood pressure is relatively low, so seals quickly • Most clinical procedures to diagnose many disorders examine venous blood • CLINICAL MODULE 17.9: Blood disorders and diseases Nutritional blood disorders – Iron deficiency anemia • RBCs cannot synthesize functional hemoglobin and are unusually small (microcytic) because iron reserves or intake is too low – – Women are especially susceptible since their iron reserves are half that of typical man Pernicious anemia • • Deficiency of vitamin B12 preventing normal stem cell divisions in red bone marrow Few RBCs and often misshapen and large (macrocytic) CLINICAL MODULE 17.9: Blood disorders and diseases • Nutritional blood disorders (continued) – Clotting disorders • Reduced calcium or vitamin K can lead to clotting disorders since they are involved in many steps of the clotting process CLINICAL MODULE 17.9: Blood disorders and diseases • Congenital blood disorders – Sickle cell anemia • Sickle-shaped RBCs due to affected amino acid sequence in Hb beta chains – • Affected cells are fragile and can block vessels Individuals with disorder must have two copies of sickling gene – Those with one copy have the sickling trait but not disorder » Have increased resistance to malaria • CLINICAL MODULE 17.9: Blood disorders and diseases Congenital blood disorders (continued) – Hemophilia • • • • Inherited bleeding disorder Malfunctioning clotting cascade due to reduced production of single clotting factor Severity of disorder varies 1 person out of 10,000 affected – – 80%–90% males Thalassemias • Diverse group of inherited disorders caused by inability to adequately produce normal Hb protein subunits Normal and sickled RBCs characteristic of the congenital blood disorder called sickle cell anemia Figure 17.9 2 CLINICAL MODULE 17.9: Blood disorders and diseases • Infections of the blood – Pathogens entering the blood through wound or infection – Bacteremia • Bacteria circulating in blood but not multiplying there – Viremia • Viruses circulating in blood but not multiplying there – Septicemia • Pathogens present and multiplying in blood and spreading The legs on an infant with septicemia (a blood infection) caused by meningococcal bacteria) Figure 17.9 2 CLINICAL MODULE 17.9: Blood disorders and diseases • Infections of the blood (continued) – Malaria • • • Parasitic disease caused by several species of the protozoan Plasmodium Kills 1.5–3 million people per year, up to half children Initially infects liver but fragments infect RBCs – – Periodically (2–3 days), all RBCs rupture and release more parasites Dead RBCs block vessels to vital organs A mosquito biting a human, and an RBC infected with the protozoan parasite Plasmodium, the organism that causes malaria Figure 17.9 2 CLINICAL MODULE 17.9: Blood disorders and diseases • Tumors of the blood – Leukemia (cancers of blood-forming tissues) • Cancerous cells spread throughout body from their origin in red bone marrow – • First symptoms appear with presence of immature and abnormal WBCs in circulation Two types 1. 2. Myeloid leukemia (abnormal levels of granulocytes) Lymphoid leukemia (abnormal levels of lymphocytes and stem cells) Abnormal WBCs (marked with red dots) in a blood smear of an individual with the cancer called myeloid leukemia Figure 17.9 2 CLINICAL MODULE 17.9: Blood disorders and diseases • Degenerative blood disorders – Disseminated intravascular coagulation (DIC) • Bacterial toxins activate clotting process steps – – • Converts too much fibrinogen to fibrin » Small clots may appear in small vessels Phagocytes and plasmin work to remove fibrin Liver works to keep fibrinogen at adequate levels – Uncontrolled bleeding may occur without enough fibrinogen CLINICAL MODULE 17.9 Review a. Define venipuncture. b. Identify the two types of leukemia. c. Compare pernicious anemia with iron deficiency anemia.