Composition of Blood Consists of formed elements (cells) suspended & carried in plasma (fluid part) Total blood volume is about 5L Plasma is straw-colored liquid consisting of H 2 0 & dissolved solutes –Includes ions, metabolites, hormones, antibodies 13-7

Plasma Proteins Constitute 7-9% of plasma Three types of plasma proteins: albumins, globulins, & fibrinogen –Albumin accounts for 60-80% Creates colloid osmotic pressure that draws H 2 0 from interstitial fluid into capillaries to maintain blood volume & pressure Globulins carry lipids –Gamma globulins are antibodies Fibrinogen serves as clotting factor –Converted to fibrin –Serum is fluid left when blood clots 13-8

Formed Elements Are erythrocytes (RBCs) & leukocytes (WBCs) RBCs are flattened biconcave discs –Shape provides increased surface area for diffusion –Lack nuclei & mitochondria –Each RBC contains 280 million hemoglobins Fig

Leukocytes Have nucleus, mitochondria, & amoeboid ability Can squeeze through capillary walls (diapedesis) –Granular leukocytes help detoxify foreign substances & release heparin Include eosinophils, basophils, & neutrophils Fig

Leukocytes continued Agranular leukocytes are phagocytic & produce antibodies Include lymphocytes & monocytes Fig

Platelets (thrombocytes) Are smallest of formed elements, lack nucleus Are fragments of megakaryocytes; amoeboid Constitute most of mass of blood clots Release serotonin to vasoconstrict & reduce blood flow to clot area Secrete growth factors to maintain integrity of blood vessel wall Survive 5-9 days Fig

Hematopoiesis Is formation of blood cells from stem cells in marrow (myeloid tissue) & lymphoid tissue Erythropoiesis is formation of RBCs –Stimulated by erythropoietin (EPO) from kidney Leukopoiesis is formation of WBCs –Stimulated by variety of cytokines = autocrine regulators secreted by immune system 13-13

Erythropoiesis 2.5 million RBCs are produced/sec Lifespan of 120 days Old RBCs removed from blood by phagocytic cells in liver, spleen, & bone marrow –Iron recycled back into hemoglobin production Fig

RBC Antigens & Blood Typing Antigens present on RBC surface specify blood type Major antigen group is ABO system –Type A blood has only A antigens –Type B has only B antigens –Type AB has both A & B antigens –Type O has neither A or B antigens Click here to play ABO Blood Types RealMedia Movie

Transfusion Reactions People with Type A blood make antibodies to Type B RBCs, but not to Type A Type B blood has antibodies to Type A RBCs but not to Type B Type AB blood doesn’t have antibodies to A or B Type O has antibodies to both Type A & B If different blood types are mixed, antibodies will cause mixture to agglutinate Fig

Transfusion Reactions continued If blood types don't match, recipient’s antibodies agglutinate donor’s RBCs Type O is “universal donor” because lacks A & B antigens –Recipient’s antibodies won’t agglutinate donor’s Type O RBCs Type AB is “universal recipient” because doesn’t make anti-A or anti-B antibodies –Won’t agglutinate donor’s RBCs Insert fig Fig

Hemostasis Is cessation of bleeding Promoted by reactions initiated by vessel injury: –Vasoconstriction restricts blood flow to area –Platelet plug forms Plug & surroundings are infiltrated by web of fibrin, forming clot 13-19

Role of Platelets Platelets don't stick to intact endothelium because of presence of prostacyclin (PGI 2 --a prostaglandin) & NO –Keep clots from forming & are vasodilators Fig 13.7a

Role of Platelets Damage to endothelium allows platelets to bind to exposed collagen –von Willebrand factor increases bond by binding to both collagen & platelets –Platelets stick to collagen & release ADP, serotonin, & thromboxane A 2 = platelet release reaction Fig 13.7b

Role of Platelets continued Serotonin & thromboxane A 2 stimulate vasoconstriction, reducing blood flow to wound ADP & thromboxane A 2 cause other platelets to become sticky & attach & undergo platelet release reaction –This continues until platelet plug is formed Fig 13.7c

Platelet plug becomes infiltrated by meshwork of fibrin Clot now contains platelets, fibrin & trapped RBCs –Platelet plug undergoes plug contraction to form more compact plug Role of Fibrin 13-23

Can occur via 2 pathways: –Intrinsic pathway clots damaged vessels & blood left in test tube Initiated by exposure of blood to negatively charged surface of glass or blood vessel collagen –This activates factor XII (a protease) which initiates a series of clotting factors –Ca 2+ & phospholipids convert prothrombin to thrombin »Thrombin converts fibrinogen to fibrin which polymerizes to form a mesh –Damage outside blood vessels releases tissue thromboplastin that triggers a clotting shortcut (= extrinsic pathway) Conversion of Fibrinogen to Fibrin 13-24

Fig

Dissolution of Clots When damage is repaired, activated factor XII causes activation of kallikrein –Kallikrein converts plasminogen to plasmin Plasmin digests fibrin, dissolving clot 13-26

Anticoagulants Clotting can be prevented by Ca +2 chelators (e.g. sodium citrate or EDTA) –or heparin which activates antithrombin III (blocks thrombin) Coumarin blocks clotting by inhibiting activation of Vit K –Vit K works indirectly by reducing Ca +2 availability 13-27

Prostaglandins (PGs) Are produced in almost every organ Belong to eicosanoid family -- all derived from arachidonic acid of plasma membrane Fig

Have wide variety of functions –Different PGs may exert antagonistic effects in tissues Some promote smooth muscle contraction & some relaxation Some promote clotting; some inhibit –Promotes inflammatory process of immune system –Plays role in ovulation –Inhibits gastric secretion in digestive system Prostaglandins (PGs) continued 11-73

Cyclooxygenase (COX) 1 & 2 are involved in PG synthesis (Fig 11.34) –Are targets of a number of inhibitory non-steroidal anti- inflammatory drugs (NSAIDs) Aspirin, indomethacin, ibuprofen inhibit both COX 1 & 2 thereby producing side effects Celebrex & Vioxx only inhibit COX 2 & thus have few side effects Prostaglandins (PGs) continued 11-74