1. University of Jordan1 Body Fluids & Blood

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5. 5 Movement of water between compartments Normally, cells neither shrink or swell because intracellular and interstitial fluids have the same osmolarity  Increasing osmolarity of interstitial fluid draws water out of cells and cells shrink  Decreasing osmolarity of interstitial fluid causes cells to swell Changes in osmolarity most often result from changes in Na + concentration Water intoxication – drinking water faster than the kidneys can excrete it  Can lead to convulsions, coma or death

6. University of Jordan6 Electrolytes in body fluids  Ions form when electrolytes dissolve ad dissociate  4 general functions Control osmosis of water between body fluid compartments Help maintain the acid-base balance Carry electrical current Serve as cofactors

7. University of Jordan7 Concentrations in body fluids Concentration of ions typically expressed in milliequivalents per liter (mEq/liter)  Na + or Cl - number of mEq/liter = mmol/liter  Ca 2+ or HPO 4 2- number of mEq/liter = 2 x mmol/liter Chief difference between 2 ECF compartments (plasma and interstitial fluid) is plasma contains many more protein anions  Largely responsible for blood colloid osmotic pressure

8. University of Jordan8 ICF differs considerably from ECF  ECF most abundant cation is Na +, anion is Cl -  ICF most abundant cation is K +, anion are proteins and phosphates (HPO 4 2- )  Na + /K + pumps play major role in keeping K + high inside cells and Na + high outside cell

9. University of Jordan9 Sodium Na + Most abundant ion in ECF 90% of extracellular cations Plays pivotal role in fluid and electrolyte balance because it account for almost half of the osmolarity of ECF Level in blood controlled by  Aldosternone – increases renal reabsorption  ADH – if sodium too low, ADH release stops  Atrial natriuretic peptide – increases renal excretion

10. University of Jordan10 Chloride Cl - Most prevalent anions in ECF Moves relatively easily between ECF and ICF because most plasma membranes contain Cl - leakage channels and antiporters Can help balance levels of anions in different fluids  Chloride shift in RBCs Regulated by  ADH – governs extent of water loss in urine  Processes that increase or decrease renal reabsorption of Na + also affect reabsorption of Cl -

11. University of Jordan11 Potassium K + Most abundant cations in ICF Key role in establishing resting membrane potential in neurons and muscle fibers Also helps maintain normal ICF fluid volume Helps regulate pH of body fluids when exchanged for H + Controlled by aldosterone – stimulates principal cells in renal collecting ducts to secrete excess K +

12. University of Jordan12 Bicarbonate HCO 3 - Second most prevalent extracellular anion Concentration increases in blood passing through systemic capillaries picking up carbon dioxide  Carbon dioxide combines with water to form carbonic acid which dissociates  Drops in pulmonary capillaries when carbon dioxide exhaled Chloride shift helps maintain correct balance of anions in ECF and ICF Kidneys are main regulators of blood HCO 3 -  Can form and release HCO 3 - when low or excrete excess

13. University of Jordan13 Blood  Liquid connective tissue  3 general functions 1. Transportation Gases, nutrients, hormones, waste products 2. Regulation pH, body temperature, osmotic pressure 3. Protection Clotting, white blood cells, proteins

14. University of Jordan14 Components of Blood Blood plasma – water liquid extracellular matrix  91.5% water, 8.5% solutes (primarily proteins)  Hepatocytes synthesize most plasma proteins  Albumins, fibrinogen, antibodies  Other solutes include electrolytes, nutrients, enzymes, hormones, gases and waste products Formed elements – cells and cell fragments  Red blood cells (RBCs)  White blood cells (WBCs)  Platelets

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16. University of Jordan16 Composition of Blood  Plasma: Straw-colored liquid.  Consists of H 2 0 and dissolved solutes.  Ions, metabolites, hormones, antibodies.  Na + is the major solute of the plasma.  Plasma proteins: Constitute 7-9% of plasma.  Albumin:  Accounts for 60-80% of plasma proteins.  Provides the colloid osmotic pressure needed to draw H 2 0 from interstitial fluid to capillaries.  Maintains blood pressure.

17. University of Jordan17  Plasma proteins (continued): Globulins:  a globulin:  Transport lipids and fat soluble vitamins.  b globulin:  Transport lipids and fat soluble vitamins.  g globulin:  Antibodies that function in immunity.  Fibrinogen: Constitutes 4% of plasma proteins. Important clotting factor.  Converted into fibrin during the clotting process. Composition of the Blood (continued)

18. University of Jordan18  Serum: Fluid from clotted blood.  Does not contain fibrinogen.  Plasma volume: Number of regulatory mechanisms in the body maintain homeostasis of plasma volume.  Osmoreceptors.  ADH.  Renin-angiotensin-aldosterone system. Composition of the Blood (continued)

19. University of Jordan19 Formed Elements of Blood

20. University of Jordan20 Formation of Blood Cells  Negative feedback systems regulate the total number of RBCs and platelets in circulation  Abundance of WBC types based of response to invading pathogens or foreign antigens  Hemopoiesis or hemotopoiesis  Red bone marrow primary site  Pluripotent stem cells have the ability to develop into many different types of cells

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22. University of Jordan22 Formation of Blood Cells  Pluripotent stem cells produce Myeloid stem cells  Give rise to red blood cells, platelets, monocytes, neutrophils, eosinophils and basophils Lymphoid stem cells give rise to  Lymphocytes  Hemopoietic growth factors regulate differentiation and proliferation Erythropoietin – RBCs Thrombopoietin – platelets Colony-stimulating factors (CSFs) and interleukins – WBCs

23. University of Jordan23 Leukopoiesis  Cytokines stimulate different types and stages of WBC production.  Multipotent growth factor-1, interleukin-1, and interleukin- 3: Stimulate development of different types of WBC cells.  Granulocyte-colony stimulating factor (G-CSF): Stimulates development of neutrophils.  Granulocyte-monocyte colony stimulating factor (GM- CSF): Simulates development of monocytes and eosinophils.

24. University of Jordan24 Erythrocytes  Flattened biconcave discs.  Provide increased surface area through which gas can diffuse.  Lack nuclei and mitochondria. Half-life ~ 120 days.  Each RBC contains 280 million hemoglobin with 4 heme chains (contain iron).  Removed from circulation by phagocytic cells in liver, spleen, and bone marrow.

25. University of Jordan25 Leukocytes  Contain nuclei and mitochondria.  Move in amoeboid fashion. Can squeeze through capillary walls (diapedesis).  Almost invisible, so named after their staining properties. Granular leukocytes:  Help detoxify foreign substances.  Release heparin. Agranular leukocytes:  Phagocytic.  Produce antibodies.

26. University of Jordan26 Platelets (thrombocytes)  Smallest of formed elements. Are fragments of megakaryocytes. Lack nuclei.  Capable of amoeboid movement.  Important in blood clotting: Constitute most of the mass of the clot. Release serotonin to vasoconstrict and reduce blood flow to area.  Secrete growth factors: Maintain the integrity of blood vessel wall.  Survive 5-9 days.

27. University of Jordan27 Blood Cells and Platelets

28. University of Jordan28 Hematopoiesis  Undifferentiated cells gradually differentiate to become stem cells, that form blood cells.  Occurs in myeloid tissue (bone marrow of long bones) and lymphoid tissue.  2 types of hematopoiesis: Erythropoiesis:  Formation of RBCs. Leukopoiesis:  Formation of WBCs.

29. University of Jordan29 Erythropoiesis  Active process. 2.5 million RBCs are produced every second.  Primary regulator is erythropoietin. Binds to membrane receptors of cells that will become erythroblasts. Erythroblasts transform into normoblasts. Normoblasts lose their nuclei to become reticulocytes. Reticulocytes change into mature RBCs.  Stimulates cell division.  Old RBCs are destroyed in spleen and liver. Iron recycled back to myeloid tissue to be reused in hemoglobin production.  Need iron, vitamin B 12 and folic acid for synthesis.

30. University of Jordan30 Red Blood Cells/ Erythrocytes  Contain oxygen-carrying protein hemoglobin  Production = destruction with at least 2 million new RBCs per second  Biconcave disc – increases surface area  Strong, flexible plasma membrane  Glycolipids in plasma membrane responsible for ABO and Rh blood groups  Lack nucleus and other organelles No mitochondria – doesn’t use oxygen

31. University of Jordan31 Hemoglobin Globin – 4 polypeptide chains Heme in each of 4 chains Iron ion can combine reversibly with one oxygen molecule Also transports 23% of total carbon dioxide  Combines with amino acids of globin Nitric oxide (NO) binds to hemoglobin  Releases NO causing vasodilation to improve blood flow and oxygen delivery

32. University of Jordan32 Shapes of RBC and Hemoglobin

33. University of Jordan33 Red Blood Cells  RBC life cycle Live only about 120 days Cannot synthesize new components – no nucleus Ruptured red blood cells removed from circulation and destroyed by fixed phagocytic macrophages in spleen and liver Breakdown products recycled  Globin’s amino acids reused  Iron reused  Non-iron heme ends as yellow pigment urobilin in urine or brown pigment stercobilin in feces

34. University of Jordan34 Red blood cell death and phagocytosis Key: in blood in bile Macrophage in spleen, liver, or red bone marrow 1 Globin Red blood cell death and phagocytosis Key: in blood in bile Macrophage in spleen, liver, or red bone marrow Heme 2 1 Amino acids Reused for protein synthesis Globin Red blood cell death and phagocytosis Key: in blood in bile Macrophage in spleen, liver, or red bone marrow Heme 3 2 1 Amino acids Reused for protein synthesis Globin Red blood cell death and phagocytosis Transferrin Fe 3+ Key: in blood in bile Macrophage in spleen, liver, or red bone marrow Heme 4 3 2 1 Amino acids Reused for protein synthesis Globin Red blood cell death and phagocytosis Transferrin Fe 3+ Liver Key: in blood in bile Macrophage in spleen, liver, or red bone marrow Ferritin Heme 5 4 3 2 1 Amino acids Reused for protein synthesis Globin Red blood cell death and phagocytosis Transferrin Fe 3+ Transferrin Liver Key: in blood in bile Macrophage in spleen, liver, or red bone marrow Ferritin Heme 6 5 4 3 2 1 Amino acids Reused for protein synthesis Globin Red blood cell death and phagocytosis Transferrin Fe 3+ Transferrin Liver + Globin + Vitamin B 12 + Erythopoietin Key: in blood in bile Macrophage in spleen, liver, or red bone marrow Ferritin Heme Fe 3+ 7 6 5 4 3 2 1 Amino acids Reused for protein synthesis Globin Circulation for about 120 days Red blood cell death and phagocytosis Transferrin Fe 3+ Transferrin Liver + Globin + Vitamin B 12 + Erythopoietin Key: in blood in bile Erythropoiesis in red bone marrow Macrophage in spleen, liver, or red bone marrow Ferritin Heme Fe 3+ 8 7 6 5 4 3 2 1 Amino acids Reused for protein synthesis Globin Circulation for about 120 days Red blood cell death and phagocytosis Transferrin Fe 3+ Transferrin Liver + Globin + Vitamin B 12 + Erythopoietin Key: in blood in bile Erythropoiesis in red bone marrow Macrophage in spleen, liver, or red bone marrow Ferritin Heme Biliverdin Bilirubin Fe 3+ 9 8 7 6 5 4 3 2 1 Amino acids Reused for protein synthesis Globin Circulation for about 120 days Bilirubin Red blood cell death and phagocytosis Transferrin Fe 3+ Transferrin Liver + Globin + Vitamin B 12 + Erythopoietin Key: in blood in bile Erythropoiesis in red bone marrow Macrophage in spleen, liver, or red bone marrow Ferritin Heme Biliverdin Bilirubin Fe 3+ 10 9 8 7 6 5 4 3 2 1 Amino acids Reused for protein synthesis Globin Stercobilin Bilirubin Urobilinogen Feces Small intestine Circulation for about 120 days Bacteria Bilirubin Red blood cell death and phagocytosis Transferrin Fe 3+ Transferrin Liver + Globin + Vitamin B 12 + Erythopoietin Key: in blood in bile Erythropoiesis in red bone marrow Macrophage in spleen, liver, or red bone marrow Ferritin Heme Biliverdin Bilirubin Fe 3+ 12 11 10 9 8 7 6 5 4 3 2 1 Amino acids Reused for protein synthesis Globin Urine Stercobilin Bilirubin Urobilinogen Feces Small intestine Circulation for about 120 days Bacteria Bilirubin Red blood cell death and phagocytosis Transferrin Fe 3+ Transferrin Liver + Globin + Vitamin B 12 + Erythopoietin Key: in blood in bile Erythropoiesis in red bone marrow Kidney Macrophage in spleen, liver, or red bone marrow Ferritin Urobilin Heme Biliverdin Bilirubin Fe 3+ 13 12 11 10 9 8 7 6 5 4 3 2 1 Amino acids Reused for protein synthesis Globin Urine Stercobilin Bilirubin Urobilinogen Feces Large intestine Small intestine Circulation for about 120 days Bacteria Bilirubin Red blood cell death and phagocytosis Transferrin Fe 3+ Transferrin Liver + Globin + Vitamin B 12 + Erythopoietin Key: in blood in bile Erythropoiesis in red bone marrow Kidney Macrophage in spleen, liver, or red bone marrow Ferritin Urobilin Heme Biliverdin Bilirubin Fe 3+ 14 13 12 11 10 9 8 7 6 5 4 3 2 1 Formation and Destruction of RBC’s

35. University of Jordan35 Erythropoiesis Starts in red bone marrow with proerythroblast Cell near the end of development ejects nucleus and becomes a reticulocyte Develop into mature RBC within 1-2 days Negative feedback balances production with destruction Controlled condition is amount of oxygen delivery to tissues Hypoxia stimulates release of erythropoietin

37. University of Jordan37 White Blood Cells/ Leukocytes  Have nuclei  Do not contain hemoglobin  Granular or agranular based on staining highlighting large conspicuous granules  Granular leukocytes Neutrophils, eosinophils, basophils  Agranular leukocytes Lymphocytes and monocytes

38. University of Jordan38 Types of White Blood Cells

39. University of Jordan39 Functions of WBCs Usually live a few days Except for lymphocytes – live for months or years Far less numerous than RBCs Leukocytosis is a normal protective response to invaders, strenuous exercise, anesthesia and surgery Leukopenia is never beneficial General function to combat invaders by phagocytosis or immune responses

40. University of Jordan40 Emigration of WBCs  Many WBCs leave the bloodstream  Emigration (formerly diapedesis)  Roll along endothelium  Stick to and then squeeze between endothelial cells  Precise signals vary for different types of WBCs

41. University of Jordan41 WBCs  Neutrophils and macrophages are active phagocytes Attracted by chemotaxis  Neutrophils respond most quickly to tissue damage by bacteria Uses lysozymes, strong oxidants, defensins  Monocytes take longer to arrive but arrive in larger numbers and destroy more microbes Enlarge and differentiate into macrophages

42. University of Jordan42 WBCs  Basophila leave capillaries and release granules containing heparin, histamine and serotonin, at sites of inflammation Intensify inflammatory reaction Involved in hypersensitivity reactions (allergies)  Eosinophils leave capillaries and enter tissue fluid Release histaminase, phagocytize antigen-antibody complexes and effective against certain parasitic worms

43. University of Jordan43 Lymphocytes  Lymphocytes are the major soldiers of the immune system B cells – destroying bacteria and inactivating their toxins T cells – attack viruses, fungi, transplanted cells, cancer cells and some bacteria Natural Killer (NK) cells – attack a wide variety of infectious microbes and certain tumor cells

44. University of Jordan44 Platelets/ Thrombocytes  Myeloid stem cells develop eventually into a megakaryocyte  Splinters into 2000-3000 fragments  Each fragment enclosed in a piece of plasma membrane  Disc-shaped with many vesicles but no nucleus  Help stop blood loss by forming platelet plug  Granules contain blood clot promoting chemicals  Short life span – 5-9 days

45. University of Jordan45 Stem cell transplants  Bone marrow transplant Recipient's red bone marrow replaced entirely by healthy, noncancerous cells to establish normal blood cell counts Takes 2-3 weeks to begin producing enough WBCs to fight off infections Graft-versus-host-disease – transplanted red bone marrow may produce T cells that attack host tissues  Cord-blood transplant Stem cells obtained from umbilical cord shortly before birth Easily collected and can be stored indefinitely Less likely to cause graft-versus-host-disease

46. University of Jordan46 Hemostasis  Sequence of responses that stops bleeding  3 mechanisms reduce blood loss 1. Vascular spasm Smooth muscle in artery or arteriole walls contracts 2. Platelet plug formation Platelets stick to parts of damaged blood vessel, become activated and accumulate large numbers 3. Blood clotting (coagulation)

47. University of Jordan47 Platelet Plug Formation

48. University of Jordan48 Blood Clotting 3. Blood clotting Serum is blood plasma minus clotting proteins Clotting – series of chemical reactions culminating in formation of fibrin threads Clotting (coagulation) factors – Ca 2+, several inactive enzymes, various molecules associated with platelets or released by damaged tissues

49. University of Jordan49 3 Stages of Clotting 1. Extrinsic or intrinsic pathways lead to formation of prothrombinase 2. Prothrombinase converts prothrombin into thrombin 3. Thrombin converts fibrinogen (soluble) into fibrin (insoluble) forming the threads of the clot

50. University of Jordan50 Blood Clotting  Extrinsic pathway Fewer steps then intrinsic and occurs rapidly Tissue factor (TF) or thromboplastin leaks into the blood from cells outside (extrinsic to) blood vessels and initiates formation of prothrombinase  Intrinsic pathway More complex and slower than extrinsic Activators are either in direct contact with blood or contained within (intrinsic to) the blood Outside tissue damage not needed Also forms prothrombinase

51. University of Jordan51 Blood Clotting: Common pathway Marked by formation of prothrombinase Prothrombinase with Ca 2+ catalyzes conversion of prothrombin to thrombin Thrombin with Ca 2+ converts soluble fibrinogen into insoluble fibrin Thrombin has 2 positive feedback effects  Accelerates formation of prothrombinase  Thrombin activates platelets  Clot formation remains localized because fibrin absorbs thrombin and clotting factor concentrations are low

52. University of Jordan52 Blood Clotting  Function of platelets: Platelets normally repelled away from endothelial lining by prostacyclin (prostaglandin).  Do not want to clot normal vessels.  Damage to the endothelium wall: Exposes subendothelial tissue to the blood.

53. University of Jordan53 Blood Clotting (continued)  Platelet release reaction: Endothelial cells secrete von Willebrand factor to cause platelets to adhere to collagen. When platelets stick to collagen, they degranulate as platelet secretory granules:  Release ADP, serotonin and thromboxane A 2.  Serotonin and thromboxane A 2 stimulate vasoconstriction.  ADP and thromboxane A 2 make other platelets “sticky.”  Platelets adhere to collagen.  Stimulates the platelet release reaction.  Produce platelet plug.  Strengthened by activation of plasma clotting factors.

54. University of Jordan54  Platelet plug strengthened by fibrin.  Clot reaction: Contraction of the platelet mass forms a more compact plug. Conversion of fibrinogen to fibrin occurs.  Conversion of fibrinogen to fibrin: Intrinsic Pathway:  Initiated by exposure of blood to a negatively charged surface (collagen).  This activates factor XII (protease), which activates other clotting factors.  Ca 2+ and phospholipids convert prothrombin to thrombin.  Thrombin converts fibrinogen to fibrin.  Produces meshwork of insoluble fibrin polymers. Blood Clotting (continued)

55. University of Jordan55 Blood Clotting (continued)  Extrinsic pathway: Thromboplastin is not a part of the blood, so called extrinsic pathway. Damaged tissue releases thromboplastin.  Thromboplastin initiates a short cut to formation of fibrin.

56. University of Jordan56 Blood Clotting (continued)

57. University of Jordan57 Dissolution of Clots  Activated factor XII converts an inactive molecule into the active form (kallikrein). Kallikrein converts plasminogen to plasmin.  Plasmin is an enzyme that digests the fibrin. Clot dissolution occurs.  Anticoagulants: Heparin:  Activates antithrombin III. Coumarin:  Inhibits cellular activation of vitamin K.

58. University of Jordan58 Blood Groups and Blood Types  Agglutinogens – surface of RBCs contain genetically determined assortment of antigens  Blood group – based on presence or absence of various antigens  At least 24 blood groups and more than 100 antigens ABO and Rh

59. University of Jordan59 RBC Antigens and Blood Typing  Each person’s blood type determines which antigens are present on their RBC surface.  Major group of antigens of RBCs is the ABO system: Type AB: Both A and B antigens present. Type O: Neither A or B antigens present. Type A: Only A antigens present. Type B: Only B antigens present.

60. University of Jordan60 RBC Antigens and Blood Typing (continued)  Each person inherits 2 genes that control the production of ABO groups. Type A: May have inherited A gene from each parent. May have inherited A gene from one parent and O gene from the other. Type B: May have inherited B gene from each parent. May have inherited B gene from one parent and O gene from the other parent. Type AB: Inherited the A gene from one parent and the B gene from the other parent. Type O: Inherited O gene from each parent.

61. University of Jordan61 ABO Blood Group Based on A and B antigens Type A blood has only antigen A Type B blood has only antigen B Type AB blood has antigens A and B  Universal recipients – neither anti-A or anti-B antibodies Type O blood has neither antigen  Universal donor Reason for antibodies presence not clear

62. University of Jordan62 Antigens and Antibodies of ABO Blood Types

63. University of Jordan63 Rh Factor  Another group of antigens found on RBCs.  Rh positive: Has Rho(D) antigens.  Rh negative: Does not have Rho(D) antigens.  Significant when Rh- mother gives birth to Rh+ baby. At birth, mother may become exposed to Rh+ blood of fetus.  Mother at subsequent pregnancies may produce antibodies against the Rh factor.  Erythroblastosis fetalis: Rh- mother produces antibodies, which cross placenta.  Hemolysis of Rh+ RBCs in the fetus.

64. University of Jordan64  Rh blood group People whose RBCs have the Rh antigen are Rh + People who lack the Rh antigen are Rh - Normally, blood plasma does not contain anti-RH antibodies Hemolytic disease of the newborn (HDN) – if blood from Rh + fetus contacts Rh - mother during birth, anti-Rh antibodies made  Affect is on second Rh + baby Hemolytic Disease

65. University of Jordan65 Typing Blood Single drops of blood are mixed with different antisera Agglutination with an antisera indicates the presence of that antigen on the RBC

66. University of Jordan66 Transfusion Reactions  If blood types do not match, the recipient’s antibodies attach to donor’s RBCs and agglutinate.  Type O: Universal donor:  Lack A and B antigens.  Recipient’s antibodies cannot agglutinate the donor’s RBCs.  Type AB: Universal recipient:  Lack the anti-A and anti-B antibodies. Cannot agglutinate donor’s RBCs.  Insert fig. 13.6

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