Chapter 19: Blood

Homeostasis Transports O2, CO2, nutrients, & hormones to & from body cells Helps to regulate pH & temperature Provides protection against disease

Figure 19-1 The Composition of Whole Blood.

White Bood Cells (WBCs) Hemopoiesis Red bone marrow Hemocytoblasts (Hematopoietic stem cells) Myeloid Stem Cells Lymphoid Stem Cells Progenitor Cells EPO GM-CSF G-CSF M-CSF Blast Cells Proerythroblast Erythroblast stages Reticulocyte Erythrocyte Ejection of nucleus Red Blood Cells (RBCs) White Bood Cells (WBCs) Myelocytes Band Cells Megakaryocyte Myeloblast Monoblast Lymphoblast Platelets Promonocyte Prolymphocyte Basophil Eosinophil Neutrophil Monocyte Lymphocyte Granulocytes Agranulocytes

Erythrocytes RBCs Contain hemoglobin which carries O2 Production = destruction Males have about 5.4million/ul Females have about 4.8 million/ul

Figure 19-2 The Anatomy of Red Blood Cells. LM × 477 Colorized SEM × 2100 Red blood cells 7.2–8.4 μm Blood smear a When viewed in a standard blood smear, RBCs appear as two-dimensional objects, because they are flattened against the surface of the slide. b The three-dimensional shape of RBCs. c A sectional view of a mature RBC, showing the normal ranges for its dimensions. Red blood cell (RBC) Rouleau (stacked RBCs) Nucleus of endothelial cell Blood vessels (viewed in longitudinal section) LM × 1430 Sectioned capillaries d When traveling through relatively narrow capillaries, RBCs may stack like dinner plates.

Clinical Note 19-1 Abnormal Hemoglobin. Sickling in Red Blood Cells

Hemoglobin β chain 1 α chain 1 Heme β chain 2 Heme α chain 2 Hemoglobin molecule

Figure 19-4 Recycling of Red Blood Cell Components. Events Occurring in Macrophages Events Occurring in the Red Bone Marrow Macrophages monitor the condition of circulating RBCs, engulfing them before they hemolyze (rupture), or removing Hb molecules, iron, and cell fragments from the RBCs that hemolyze in the bloodstream. Developing RBCs absorb amino acids and Fe2+ from the bloodstream and synthesize new Hb molecules. Macrophages in spleen, Liver, and red bone marrow RBC formation Fe2+ Fe2+ transported in bloodstream by transferrin Heme Amino acids Average life span of RBC is 120 days 90% Biliverdin New RBCs released into bloodstream Old and damaged RBCs Bilirubin 10% In the bloodstream, The rupture of RBCs Is called hemolysis. Bilirubin bound to albumin in bloodstream Hemoglobin that is not phagocytized breaks down, and the alpha and beta chains are eliminated in urine. Liver Kidney Bilirubin Hb Absorbed into the bloodstream Urobilins Excreted in bile Eliminated In urine Urobilins, stercobilins Bilirubin Events Occurring in the Kidney Events Occurring in the Liver Events Occurring in the Large Intestine Eliminated in feces Bilirubin released from macrophages binds to albumin and is transported to the liver for excretion in bile. Bacteria convert bilirubin to urobilins and stercobilins. Feces are yellow-brown or brown due to the presence of urobilins and stercobilins in varying proportions. The kidneys excrete some hemoglobin, as well as urobilins, which gives urine its yellow color.

Day 2: Basophilic erythroblast Day 3: Polychromatophilic erythroblast RED BONE MARROW Day 1: Proerythroblast Day 2: Basophilic erythroblast Erythroblasts Day 3: Polychromatophilic erythroblast Day 4: Normoblast Ejection of nucleus Days 5–7: Reticulocyte Enters bloodstream Erythropoiesis Hypoxia (cellular O2 deficiency) main stimulus for production Caused by High altitude Anemia Circulatory problems Mature red blood cell

Table 19-1 RBC Tests and Related Terminology.

Table 19-3 Formed Elements of the Blood (Part 1 of 4).

Leukocytes WBCs Granular Agranular Monocytes Neutrophils Eosinophils Basophils Agranular Monocytes Migrate into tissues where they differentiate into macrophages Lymphocytes LM × 1500 d RBC Eosinophil Basophil Monocyte Lymphocyte Neutrophil c b a e

Functions of WBCs Fight pathogens by phagocytosis or immune responses Leave bloodstream & move into tissue Emigration or diapedesis Use adhesion molecules to accomplish this

Table 19-3 Formed Elements of the Blood (Part 2 of 4).

Table 19-3 Formed Elements of the Blood (Part 3 of 4).

Platelets Large cell, megakaryocyte, fragments creating small pieces containing vesicles Chemicals in vesicles promote blood clotting

Table 19-3 Formed Elements of the Blood (Part 4 of 4).

Hemostasis Responses that stop bleeding 1 2 3 4 Vascular Phase Platelet Phase Coagulation Phase Clot Retraction 1 2 3 4 The vascular phase of hemostasis lasts for about 30 minutes after the injury occurs. The endothelial cells contract and release endothelins, which stimulate smooth muscle contraction and endothelial division. The endothelial cells become “sticky” and adhere to platelets and each other. The platelet phase of hemostasis begins with the Attachment of platelets to sticky endothelial surfaces, to the basement membrane, to exposed collagen fibers, and to each other. As they become activated, platelets release a variety of chemicals that promote aggregation, vascular spasm, clotting, and vessel repair. Coagulation, or blood clotting, involves a complex sequence of steps leading to the conversion of circulating fibrinogen (a soluble protein) into fibrin (an insoluble protein). As the fibrin network grows, blood cells and additional platelets are trapped in the fibrous tangle, forming a blood clot that seals off the damaged portion of the vessel. Once the fibrin meshwork has formed, platelets and red blood cells stick to the fibrin strands. The platelets then contract, and the entire clot begins to undergo clot retraction, a process that continues over 30–60 minutes. Knife blade Blood vessel injury Vascular spasm Release of chemicals (ADP, PDGF, Ca2+, platelet factors) Plasma in vessel lumen Platelet adhesion to damaged vessel aggregation Interstitial fluid Platelet plug may form Cut edge of vessel wall Endothelium Basement membrane Vessel wall Contracted smooth muscle cells Extrinsic Pathway Common Pathway Intrinsic Pathway Tissue factor complex Clotting factor (VII) (Factor III) Tissue damage Activated proenzymes (usually Factor XII) factor (PF-3) Clotting factors (VIII, IX) Factor X activator Prothrombin Thrombin Fibrin Fibrinogen Ca2+ Blood clot containing trapped RBCs SEM × 1200

Vascular Spasm Contraction of smooth muscle in vessel wall Knife blade Blood vessel injury Vascular spasm 1 The vascular phase of hemostasis lasts for about 30 minutes after the injury occurs. The endothelial cells contract and release endothelins, which stimulate smooth muscle contraction and endothelial division. The endothelial cells become “sticky” and adhere to platelets and each other. Vascular Phase Contraction of smooth muscle in vessel wall Probably due to Damage to muscle Substances released from platelets Reflexes from pain receptors

Platelet Plug Formation Endothelium 2 The platelet phase of hemostasis begins with the attachment of platelets to sticky endothelial surfaces, to the basement membrane, to exposed collagen fibers, and to each other. As they become activated, platelets release a variety of chemicals that promote aggregation, vascular spasm, clotting, and vessel repair. Platelet Phase Vessel wall Plasma in vessel lumen Interstitial fluid Platelet adhesion to damaged vessel Platelet aggregation Platelet plug may form Cut edge of vessel wall Contracted smooth muscle cells Release of chemicals (ADP, PDGF, Ca2+, platelet factors) Platelet adhesion Stick to collagen Platelet release reaction Release of chemicals in vesicles Platelet aggregation Large numbers of platelets stick forming platelet plug Basement membrane

Coagulation Blood clotting Series of chemical reactions that end in formation of fibrin If blood clots too easily, have thrombosis If blood clotting takes too long, have hemorrhage

Coagulation 3 stages Extrinsic pathway Intrinsic pathway Extrinsic & intrinsic pathways lead to formation of prothrombinase (prothrombin activator) Prothrombinase converts prothrombin to thrombin Thrombin converts fibrinogen to fibrin Extrinsic pathway Occurs rapidly Tissue factor leaks into blood from outside vessel Intrinsic pathway Occurs more slowly Its activators are either in direct contact with blood (endothelial cells) or contained within blood (platelets)

3 Coagulation Phase Extrinsic Pathway Common Pathway Intrinsic Pathway Figure 19-11 The Vascular, Platelet, and Coagulation Phases of Hemostasis and Clot Retraction (Part 3 of 4). 3 Coagulation Phase Coagulation, or blood clotting, involves a complex sequence of steps leading to the conversion of circulating fibrinogen (a soluble protein) into fibrin (an insoluble protein). As the fibrin network grows, blood cells and additional platelets are trapped in the fibrous tangle, forming a blood clot that seals off the damaged portion of the vessel. Extrinsic Pathway Common Pathway Intrinsic Pathway Factor X Prothrombin activator Tissue factor complex Factor X activator complex Prothrombin Thrombin Clotting factor (VII) Clotting factors (VIII, IX) Fibrin Fibrinogen Ca2+ Ca2+ Platelet factor (PF-3) Tissue factor (Factor III) Activated proenzymes (usually Factor XII) Tissue damage Blood clot containing trapped RBCs SEM × 1200 Contracted smooth muscle cells

Table 19-4 Clotting Factors.

Clot Retraction 4 Tightening of the fibrin clot Once the fibrin meshwork has formed, platelets and red blood cells stick to the fibrin strands. The platelets then contract, and the entire clot begins to undergo clot retraction, a process that continues over 30–60 minutes. Clot Retraction Tightening of the fibrin clot Fibrin threads contract as platelets pull on them Permanent repair can now take place

Vitamin K Required for the synthesis of 4 clotting factors Normally produced by bacteria in large intestine

Fibrinolysis Dissolution of a clot Plasminogen is incorporated into clot Tissues & blood have substances that activate plasminogen to plasmin Plasmin digests fibrin threads & inactivates some clotting factors

Other Mechanisms of Control Prostacyclin Produced by endothelial cells & WBCs Opposes action of thromboxane A2 Inhibits platelet adhesion & release Anticoagulants Antithrombin Blocks action of several factors Heparin Combines with antithrombin & increases its effectiveness Activated protein C Inactivates 2 major clotting factors

Intravascular Clotting Thrombosis Clotting in an unbroken vessel Due to Slow flow Roughened endothelial surfaces from atherosclerosis, trauma Called thrombus If dislodges & begins to flow in blood, it is an embolus This can lodge causing blockage

Blood Groups & Blood Types Genetically determined antigens on surface of RBCs Glycoproteins & glycolipids Called agglutinogens Organizes blood into different groups based on antigen on surface

ABO Blood Group Type A Type B Type AB Type O Type A blood has RBCs with surface antigen A only. Type B blood has RBCs with surface antigen B only. Type AB blood has RBCs with both A and B surface antigens. Type O blood has RBCs lacking both A and B surface antigens. 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, which will attack type A 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. a Blood type depends on the presence of surface antigens (agglutinogens) on RBC surfaces. The plasma contains antibodies (agglutinins) that will react with foreign surface antigens.

Rh Blood Group Presence or absence of Rh factor or D antigen on surface of RBCs If present = + If absent = -

Figure 19-7 Blood Type Testing. Anti-A Anti-B Anti-D A+ B+ AB+ O−

Table 19-2 Differences in Blood Group Distribution.

Figure 19-6b Blood Types and Cross-Reactions. RBC Surface antigens Opposing antibodies Agglutination (clumping) Hemolysis b In a cross-reaction, antibodies react with their target antigens causing agglutination and hemolysis of the affected RBCs.

Hemolytic Disease of the Newborn