Blood

1. Blood Chapter 18

2. Agenda • Characteristic of Blood • Components • Functions of Components • Blood Cell Formation • Clotting • Blood Typing

3. Composition and Function • Only fluid tissue • Both solid and liquid components • Connective tissue – protects, supports and binds together other body tissues • Blood – formed elements suspended in plasma • Collagen and elastin absent, but proteins visible as fibrin during clotting

4. Components of Blood • % of total volume of blood sample that is rbc = hematocrit • Men = 42-52% Women = 37%-48% • Androgens stimulate erythropoiesis • Menstrual loss • Inversely proportion to percent body fat Figure 10.1

5. Physical Characteristics • Opaque, sticky, metallic taste • Color varies depending on arterial or venous blood, O2 level • Heavier and 5x thicker than H2O = viscosity – pressure on heart? • Alkaline, pH 7.35-7.45 • Temp = 100.4°F • 8% body weight, healthy man 6 quarts • Osmolarity – molarity of dissolved particles – exchange? Edema? High BP http://singularityhub.com/2008/08/22/is-an-unlimited-supply-of-blood-and-no-more-need-for-blood-donors-around-the-corner/

6. Plasma • ~90% H2O • Dissolved substances include – nutrients, salts (electrolytes), respiratory gases, hormones, plasma proteins, Nitrogenous wastes and products of metabolism • Proteins – albumins, globulins, fibrinogens • Helps distribute heat from cell metabolism http://www.lifeshare.cc/content.aspx?ID=13

7. Plasma Proteins • Plasma proteins – most made by liver • Albumin – shuttle, buffer, viscosity and osmolarity • Not taken up by cells, unlike nutrients or other substances • Globulins – α, β, γ = Antibodies (Ab) – immunity • Fibrinogens - Clotting proteins • Remains fairly constant in healthy person • Drastic changes – stimulates liver to make more proteins • When too acidic or basic – kidneys and respiratory systems help restore to homeostasis

8. Formed Elements - RBC • Erythrocytes far out number other cells • Carry O2 in blood • Anucleate • Very few organelles • Hemoglobin – Fe bearing protein, transports O2 • Shape – SA to vol. ratio, gas exchange • Lack mitochondria • What do Mitochondria do? Figure 10.3a

9. Hemopoiesis • Occurs in red bone marrow = myeloid tissue • Where is this in adults? • # of type of cell produced depends on body’s need and stimuli • After maturation, released into blood stream • 100 billion new cells everyday!

10. Formation of formed elements • All formed elements derived from hemocytoblast (type of stem cell) in red marrow • Development differs, but once committed can’t change path • Two decendents Figure 10.4

11. Formation of RBC • Anulceate – can’t synthesize proteins, grow, or divide • Become rigid and fragment at 100-120 days • Eliminated by phagocytes in liver, spleen, and other tissues • Lost cells replaced in red marrow • Developing RBC divide many times, produce large amount of hemoglobin • Nucleus and organelles ejected, cells collapse = reticulocyte (still contains some RER) • Enter blood, w/in 2 days eject RER, become erythrocytes

12. Erythropoiesis • 2.5 million/sec • Hemocytoblast-proerythroblast-erythroblast-normoblast-reticulocyte-erythrocyte • Erythroblast first committed cell w/ receptors for erythropoietin (made by liver and kidneys) • EPO stimulates proerythroblast to differentiate into erythroblasts – multiply and make Hb – become normoblast • Normoblast ejects nucleus = reticulocyte -> leave BM -> erythrocyte in blood

13. Controlling Rate of RBC Production • Erythropoietin • Small amount in blood at all times • Kidneys and liver secrete when O2 levels in blood drop (Hypoxemia) • Targets bone marrow • High O2 depresses erythropoietin release • NOT # of RBC in blood, but O2, how effective are the RBC Figure 10.5

14. Hemoglobin in blood • The more hemoglobin in RBC, the more O2 transported • Need to consume in Fe3+ and Fe2+ from diet • Only Fe2+ absorb by sm intestine • Stomach acid converts ferric to ferrous • Hemoglobin slightly higher in men • Men 13-18g/ml • Women 12-16g/ml • Single blood cell has ~250 mil. Hemoglobin molecules • How many O2 molecules is that? http://pennhealth.com/health_info/bloodless/000210.html

15. Death of a RBC • 100-120 days cells die • Most die in spleen = Hemolysis • Rupture – PM digested by Macrophages in liver and spleen, Hb takes some work • Macrophages separate Heme from globin (AA) • Fe removed from Heme by macrophages can be reused • Heme eventually converted into bilirubin pigment by macrophages into blood – bile pigments of gall bladder

16. Sickle Cell Anemia • Anemia – loss of O2 carrying ability • Cells become sickle shaped • unload O2 • O2 is low in blood • Exercise • Stress • Anxiety • Rupture, dam vessels • 6th a.a. change in 2 β chains – glutamic acid to valine • Evolutionary advantage in areas with malaria Figure 10.3

17. Erythrocyte Disorders • Anemia • Inadequate erythropoiesis or Hb synthesis • Hemorrhagic anemia • Hemolytic anemia • Polycythemia • Primary polycythemia – cancer of red blood cell line – High RBC count, hematocrit 80% • Secondary polycythemia – concentration of RBC due to fluid loss • Smoking, air pollution, emphysema, high altitude, physical activity etc.

18. Leukocytes – White Blood Cells • Leukopoiesis – generation of WBCs • Only complete cell in blood • Body’s defense • Move in and out of blood into tissue – diapedesis • Positive chemotaxis – respond to chemicals secreted by damaged cells • Move by ameboid motion • Destroy invaders, remove dead dying cells • Remember the eye? http://www.irvingcrowley.com/cls/hemo.htm

19. Leukocytosis vs Leukopenia • WBC mobilized, body increases production • Can double w/in 2 hours • Total WBC count over 11,000 cells/mm3 is leukocytosis • Indicates infection • Low WBC count is leukopenia • Caused by drugs like corticosteriods, anticancer drugs • Diseases such as cyclical neutropenia

20. Leukemia and Infectious Mononucleosis • Excessive production of abnormal WBC • Leukemia – bone marrow cancerous, pumps out immature WBC that can’t do job, leaves person open to infectious disease • Other blood cell lines crowed out, leads to bleeding and anemia • Mononucleosis - caused by EBV.

21. WBC - Granulocytes Table 10.2 (1 of 2

22. WBC - Agranulocytes Never let monkeys eat bananas Table 10.2 (2 of 2)

23. Platelets • Not typical cell • Fragments of multinucleate megakaryocyte = thrombopoiesis • Platelets anucleate • Clotting process in plasma when blood vessels rupture or broken • Functions • Secrete procoagulants (CF) promote clotting • Vasoconstrictors – vascular spasm • Platelet plugs to stop bleeding • Dissolve blood clots • Destroy bacteria • Attract neutrophils and monocytes Figure 10.2

24. Formation of WBCs and Platelets • Also controlled by hormones • Thrombopoietin - platelets • Colony Stimulating Factor (CSF) or Interleukins - WBCs • Prompt red marrow to produce new WBC and platelets • Enhance ability of mature leukocytes to fight • Released in response to chemical signals • Inflammatory chemicals, bacterial toxins

25. Human Blood Groups • Antigen (Ag) – substance body identifies as foreign, stimulates Ab production or other means of defense • Antibodies (Ab) – proteins that recognize Ag • Agglutination – Ab bind Ag, cause clumping and then eventual lysed • 4 Blood Types • O, AB, A, B

26. Human Blood Groups • On plasma membrane of RBCs are Ag • We do not have Ab against the Ag on our own RBC Table 10.3

27. Rh Factor • Rh antigen on cell • Most humans are Rh + • Rh antibodies (anti D Ab) are not automatically formed in Rh – individuals, requires sensitization • 1st transfusion of Rh + no reaction • 2nd time and after immune response, destroys RBCs • Pregnant Rh - women get RhoGAM shot • w/o mom’s Ab can cross placenta destroy babies RBC = hemolytic disease, fetal transfusions

28. Blood Typing Figure 10.8

29. Hemostasis - Clotting • Break or tear of vessel walls • Fast, localized response • Components of plasma and some released by platelets and injured tissue • 3 steps • Vascular Spasms – short, prevent blood flow to area • Platelet Plug Formation – normally don’t stick due to prostacyclin. Collagen exposure allows platelets to stick via pseudopods • Coagulation – most important, cascade of events Figure 10.6

30. Blood Clotting • Want to convert fibrinogen into fibrin • Reaction Cascade – activation of the next molecule • CF are called procoagulants, most made by liver • PF are procoagulants made by platetes • Two pathways • Extrinsic mechanism – CF released by damaged BV and perivascular tissue • Intrinsic mechanism – CF from blood • Work together simultaneously

31. Clotting Process 3-6 mins 15 secs Positive Feedback

32. Clot Retraction • Pseudopods pull fibrin closer together pulling damage vessel together • Platelets and endothelial cells secrete Platelet-derived growth factor (PDGF) mitotic stimulant • Stimulates fibroblasts and smooth muscle • Breakdown of fibrin clot by a different positive feedback cascade

33. Prevention of Coagulation • Platelet repulsion – prostacyclin • Dilution – Thrombin always in blood, normal blood flow dilutes. When blood flow slows can accumulate and initiate clotting • Anticoagulants – suppressed by anticoagulants present in plasma • Antithrombin – liver, deactivate thrombin before acts on Fibrinogen • Heparin – basophils and mast cells, interfere with prothrombin activator, blocks thrombin from acting on fibrinogen, promotes antithrombin

34. Blood Diseases • Hemophilia – lack of clotting factors • Group of disorders • Bleeding into joints painful and debilitating • Require transfusions of plasma or injections of clotting factors • Thrombus – clot in unbroken vessel • What problems can this cause? • Free floating Thrombus = embolus • What problems when an embolus lodges somewhere?

35. The End