blood physiology

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1. DR. WILMA BUNAYOG KOU BLOOD PHYSIOLOGY

2. Blood By the end of the lecture you should be able to: State the composition of Blood State the function of red blood cells and plasma Explain the function of hemoglobin in the transport of oxygen State the function of macrophages and lymphocytes To understand the value of blood as an important factor in homeostasis

3. INTRODUCTION : GENERAL CHARACTERISTICS OF BLOOD: 1. color: bright red  oxygenated (systemic) dark red/purple  deoxygenated (venous) 2. pH: 7.35 -7.45 3. 0smolality : 285 -295 mOsm 4. Viscosity  3-4x more viscous than water 5. Almost all blood cells are found red bone marrow.

4. BLOOD FUNCTIONS: Transport function - nutrients glucose, AA, etc - waste products urea, lactic acid , creatinine - gases O 2 , CO 2 - electrolytes Na + K + Cl - Ca ++ regulation - ph buffers - temperature protection - infection WBC , antibodies - blood loss platelets, clotting factors  

5. 5 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Centrifuged Blood Sample Peripheral Blood Smear Liquid (plasma) “Buffy coat” (white blood cells and platelets) Red blood cells Red blood cells Platelets White blood cells

6. 6 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Plasma = 55% Capillary tube Plug Buffy coat Red cells = 45% (hematocrit)

7. Blood Volume and Composition Volume varies with size. Blood is about 8% of the total body weight. Average adult has 5 liters of blood Blood is 40-45 % cells This is also known as the percent packed cell volume 95% are red blood cells, remainder white blood cells and blood platelets The hematocrit is an indicator of anemia, polycythemia , and other conditions. Blood is 55 -60% plasma water, amino acids, proteins, carbohydrates, lipids, vitamins, hormones, electrolytes, wastes

8. 8 Blood (4.8%) (95.1%) (0.1%) Plasma Hormones Monocytes Basophils Eosinophils Neutrophils (54–62%) (1–3%) (<1%) (3–9%) (25–33%) Globulins Albumins (92%) (7%) N 2 O 2 CO 2 Platelets Red blood cells Proteins Nutrients Gases 45% 55% Wastes Water White blood cells Electrolytes Vitamins Lymphocytes Fibrinogen Formed elements Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

9. Composition of Blood

10. PLASMA CHARACTERISTICS: 1. Straw colored 2. mainly water (92%), plasma CHONs, nutrients, gases, non-CHON nitrogen subs, and electrolytes FUNCTIONS 1. transport of nutrients, gases and vitamins 2. regulate fluid and electrolyte balance 3. maintain pH

11. PLASMA PLASMA PROTEINS 1. most abundant dissolved substances in plasma 2. Three main plasma proteins: a. albumin – 60% of plasma CHONs, made in the liver and they help to maintain oncotic pressure, and transport certain molecules such as bilirubin and fatty acids. b. globulins – 36% of plasma CHONs i . alpha and beta – produced in the liver, transport lipids and fat soluble vitamins ii. Gamma globulins – made by lymph tissue, a type of antibody c. fibrinogen - 4% of plasma CHONs, made in the liver, help in blood coagulation

12. PLASMA NUTRIENTS AND GASES 1. Nutrients : amino acids, simple sugars, nucleotides and lipids 2. Blood gases: oxygen and carbon dioxide NONPROTEIN NITROGEN SUBSTANCES 1. contain nitrogen but are not proteins 2. include: urea, uric acid, creatine & creatinine 3. CHON digestion  amino acids 4. CHON & nucleic acid catabolism  uric acid & urea 5. creatine metabolism  creatinine

13. PLASMA PLASMA ELECTROLYTES 1. Electrolyte release ions when dissolved in water 2. include: sodium, potassium, calcium, magnesium, chloride, bicarbonate, phosphate and sulfate ions 3. Function: maintain osmotic pressure and the pH of the plasma.

14. Blood Cells 14 Blood cells originate in red marrow from hemocytoblasts or hematopoietic stem cells Stem cells can then: Give rise to more stem cells Specialize or differentiate HEMATOPOIESIS - making of blood cells ERYTHROPOIESIS - making of RBC LEUKOPOIESIS - making of WBC

15. PLURIPOTENTIAL HEMATOPOIETIC STEM CELLS

16. Hematopoiesis

17. Blood vessel Red blood cell platelet Plasma White blood cell

18. PRODUCTION OF RBC: Early embryonic life : nucleated RBC  yolk sac Middle trimester: liver main organ for production, some are produced in the spleen and lymph nodes Last month of gestation and after birth: exclusively produced in the bone marrow Bone marrow of essentially all bones produces RBCs until 5 years old Bone marrow of the long bones, except proximal portions of the humeri and tibiae no RBCs after 20 yrs old >20 yo  membranous bones , like vertebrae, sternum, ribs, ilia  less productive as age increases.

19. GENESIS OF RBC

20. FUNCTIONS OF RBC To transport Hemoglobin, which carries oxygen from the lungs to the tissues As an enzyme that catalyzes the reversible reaction between carbon dioxide (CO2) and water to form carbonic acid (H2CO3)  carbonic anhydrase As an excellent acid-base buffer

21. Characteristics of Red Blood Cells Red blood cells are: Erythrocytes Biconcave discs Able to readily squeeze through capillaries Lack nuclei and mitochondria average volume: 90 -95 cubic micrometers Normal men: 5,200,00 cubic mm Normal women: 4,700,00 cubic mm Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Top view 2.5 micrometers 7.8 micrometers Sectional view (a) (b)

22. RED BLOOD CELLS Concentrate Hemoglobin ( Hgb ) in the cell fluid: 34 grams in each 100 milliliters of cells Hematocrit ( % of blood that is cells – normally , 40-45%) and the quantity of Hgb  men : 15 grams of Hgb /100ml of cells  women: 14 grams Hgb /100ml of cells Each gram of pure Hgb  1.34 ml of Oxygen Normal man: 20ml of O2/100ml of blood Normal woman: 19 ml of O2/100 ml of blood

23. REGULATION OF RBC Regulated within narrow limits: 1. adequate number is always available to provide sufficient transport of O2 2. cells do not become so numerous that they impede blood flow Tissue oxygenation is the most essential regulator of RBC

24. Red Blood Cell Production & Its Control 25 Low blood oxygen causes the kidneys and the liver to release erythropoietin (EPO) which stimulates RBC production This is a negative feedback mechanism Within a few days many new blood cells appear in the circulating blood Low blood oxygen Liver Kidney Erythropoietin Red bone marrow + – Bloodstream Stimulation Inhibition Release into bloodstream Increased oxygen- carrying capacity Increased number of red blood cells

25. ERYTHROPOIETEN A glycoprotein, molecular wt 34,000 90% kidneys; 10% liver Epi or norepi will also stimulate erythropoietin Maximum production within 24hours  5 days Stimulation of the erythroblast

26. Dietary Factors Affecting Red Blood Cell Production Vitamin B 12 and folic acid are necessary They are required for DNA synthesis making them necessary for the growth and division of all cells Iron is also necessary It is required for hemoglobin synthesis

27. Formation of hemoglobin Synthesis of hemoglobin begin in the proerythroblast and continues into Reticulocyte Hemoglobin molecule compose of 4 hemoglobin chains There are four different chains of hemoglobin (alpha, beta, gamma and delta chain) Hemoglobin A is a combination of two alpha and two beta chain

28. FORMATION OF HEMOGLOBIN

29. Heme 8 8 Succinyl CoA Glycine** HEME SYNTHESIS ** Amino acid (building blocks of protein) synthesized in your body

30. STRUCTURE OF HEME Ferrous iron (Fe 2+ ) Protoporphyrin IX: contains 4 pyrrole rings linked together by methenyl bridges

31. Fig. 14.8 Note that, in muscle, myoglobin (Mb) binds oxygen. Mb consists of only 1 protein chain. Note the 4 protein chains that make up 1 molecule of Hb.

32. Mechanism of Transport * 4 Heme Molecules = * 4 Oxygen Molecules *Oxygenated Hemoglobin Bright Red (systemic) *Deoxygenated Hemoglobin Blue (venous circulation) HEMOGLOBIN

33. Formation of hemoglobin There are 4 iron atom in each hemoglobin molecule. Each can bind one molecule of oxygen that can be transported in each hemoglobin molecule

34. Normal iron metabolism : -The primary function is oxygen transport. -Iron is absorbed by duodenum and jejunim -Average total body iron content 4000-5000 mg. - 65% in the form of HGB, 4% myoblogin , 1% heme cpd -Iron is also stored in RE cells (BM, Spleen and liver) as hemosiderin and ferritin . -Also iron found in myglobin and myeloperoxidase and in certain electron transfer. -Iron is more stable in ferric state (Fe +++ ) than in ferrous state (Fe ++ ).

35. Overview of Normal Iron Metabolism Iron Tansport Via transferrin Iron Storage (Hepatic - major site) Hepatic uptake of transferrin bound Fe via classic transferrin receptor TfR1 (& homologous TfR2) Hepatocytes are storage reservoir for iron Taking up dietary iron from portal blood Releasing iron into the circulation via ferroportin in times of increased demand Iron Utilisation Erythropoiesis for haem synth / general cellular respiration

36. Normally the body stores iron but women need to consume more iron than men . Why ?

37. Absorption, transport, and storage of iron

38. BLOOD CELLS LIVER Bilirubin diglucuronide ( water-soluble ) 2 UDP-glucuronic acid via bile duct to intestines Stercobilin excreted in feces Urobilinogen formed by bacteria KIDNEY Urobilin excreted in urine CO Biliverdin IX  Heme oxygenase O 2 Bilirubin ( water-insoluble ) NADP + NADPH Biliverdin reductase Heme Globin Hemoglobin reabsorbed into blood Bilirubin ( water-insoluble ) via blood to the liver INTESTINE Figure 2. Catabolism of hemoglobin

39. 44 Bilirubin Bone Blood Liver Globin + Heme 3 2 1 Absorption 4 5 Macrophage Hemoglobin Iron + Biliverdin 8 6 7 Bile Red bone marrow Red blood cells produced Red blood cells circulate in bloodstream for about 120 days Old red blood cells Blood transports absorbed nutrients Nutrients from food Vitamin B 12 Folic acid Iron Small intestine Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

40. Too few, Too many Anemia – low hematocrit (below-normal oxygen-carrying capacity of the blood) Nutritional, pernicious, aplastic, renal, hemorrhagic, hemolytic Polycythemia- abnormally high hematocrit (too many RBCs in circulation) Primary, secondary

41. ANEMIAS Blood Loss Anemia - after hemorrhage , replaces the fluid portion of the plasma in 1 to 3 days. - cell concentration usually returns to normal within 3 to 6 weeks. - chronic blood loss - microcytic,hypochromic anemia Aplastic Anemia - Bone marrow aplasia means lack of functioning bone marrow. Megaloblastic Anemia - deficiency of vitamin B12, folic acid, and intrinsic factor from the stomach mucosa - atrophy of the stomach mucosa, as occurs in pernicious anemia, or loss of the entire stomach after surgical total gastrectomy

42. ANEMIAS HEMOLYTIC ANEMIA 1. hereditary spherocytosis the red cells are very small and spherical rather than being biconcave discs. 2. sickle cell anemia present in 0.3 to 1.0 % of West African and American blacks the cells have an abnormal type of hemoglobin called hemoglobin S, containing faulty beta chains in the hemoglobin molecule 3. erythroblastosis fetalis Rh-positive red blood cells in the fetus are attacked by antibodies from an Rh-negative mother.

43. GENESIS OF RBC

44. Effects of Anemia on Function of the Circulatory System Increased cardiac output Increased pumping workload of the heart during exercise, which greatly increases tissue demand for oxygen, extreme tissue hypoxia results, and acute cardiac failure ensues.

45. POLYCYTHEMIA Secondary Polycythemia > too little oxygen in the breathed air, such as at high altitudes, or because of failure of oxygen delivery to the tissues, such as in cardiac failure, the blood-forming organs automatically produce large quantities of extra red blood cells. > RBC counts 6 to 7 million/mm3, about 30 % above normal. >physiologic polycythemia , occurs in natives who live at altitudes of 14,000 to 17,000 feet, where the atmospheric oxygen is very low.

46. POLYCYTHEMIA Polycythemia Vera ( Erythremia ) > pathological condition known in which the red blood cell count may be 7 to 8 million/mm3 and the hematocrit may be 60 to 70 per cent. > caused by a genetic aberration in hemocytoblastic cells that produce the blood cells. > not only does the hematocrit increase, but the total blood volume also increases, on some occasions to almost twice normal. > the viscosity of the blood increases from the normal of 3 times the viscosity of water to 10 times that of water.

47. Effect of Polycythemia on Function of the Circulatory System increased viscosity of the blood , blood flow through the peripheral blood vessels is often very sluggish  decreases the rate of venous return to the heart. Conversely, the blood volume is greatly increased in polycythemia , which tends to increase venous return. cardiac output in polycythemia is not far from normal

48. (b) (a) a: © The McGraw-Hill Companies, Inc./Al Telser, photographer :b © Ed Reschke Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 53

49. WHITE BLOOD CELLS

50. Blood Cell Origin and Production Bone Marrow Circulation Figure 11-8

51. 5 - Types of WBC’s Each WBC has a specific function Granulocytes Agranulocytes

52. White Blood Cells (Leukocytes) Mobile units of body’s defense system: “Seek and Destroy” Functions: Destroy invading microorganisms Destroy abnormal cells ( ie : cancer ) Clean up cellular debris ( phagocytosis ) 3. Assist in injury repair

53. Phagocytosis WBC function is phagocytosis which means cellular ingestion of the offending agent Phagocytes is selective of the material that is phagocytized and depends on: Tissue surface structure Protein coats Development of antibodies This selection of phagocytosis called opsonization

54. Characteristics of WBC White Blood Cells enter the tissue spaces by Diapedesis . Neutrophils and monocytes can squeeze through the pores of the blood capillaries by diapedesis . White Blood Cells move through tissue spaces by Ameboid Motion. White Blood Cells are attracted to inflamed tissue areas by Chemotaxis

55. Movement of Leukocytes through Epithelia Protect against infection: phagocytize bacteria; produce proteins that destroy foreign particles Diapedesis: leukocytes can squeeze between cells and leave the circulation Fig. 14.14

56. Infection

57. Characteristics of WBC The adult human 7000 WBC/ ml of bld (in comparison with 5 million red blood cells).(NV: 5,000 – 6,000) The normal percentages of the different types are Polymorphonuclear neutrophils 62.0% (54 -62%) Polymorphonuclear eosinophils 2.3% (1 -3%) Polymorphonuclear basophils 0.4% ( 0.5 - 1%) Monocytes 5.3% (3 – 8%) Lymphocytes 30.0% ( 25- 35%)

58. Characteristics of WBC The life of the granulocytes normally 4 to 8 hours circulating in the blood and another 4 to 5 days in tissues . The monocytes  short transit time, 10 to 20 hours in the blood, before wandering through the capillary membranes into the tissues. Once in the tissues, they swell to much larger sizes to become tissue macrophages, and, in this form, can live for months

59. Types of WBC’s Polymorphonuclear Granulocytes Neutrophils Eosinophils Basophils

60. 1. NEUTROPHILS * 54 -62% of all leukocytes (most abundant of WBC’s) * Phagocytes that engulf bacteria and Debris * Important in inflammatory responses

61. 2. EOSINOPHILS * 1 -3 % of the WBC's * Attack parasitic worms * Control inflammation and allergic reactions

62. 3. BASOPHILS Releases histamine and heparin * 0.5 - 1% of the WBC's * Important in Allergic Reactions * Heparin anticoagulant and helps clear fat from blood

63. Types of WBC’s Mononuclear Agranulocytes 4. Monocytes 5. Lymphocytes (B and T cells)

64. 4. MONOCYTES * Exit blood (diapedesis) to become macrophages * 3 - 8 % of the WBC's * Phagocytic = defend against viruses and bacteria

65. 5. LYMPHOCYTES * B-lymphocytes: Produce Antibodies * T-lymphocytes: Directly destroy virus- invaded cells and cancer cells * 25-35 % of the WBC's

66. Charateristics Both Neutrophils and Macrophages can kill bacteria. - contain bactericidal agents that kill most bacteria Some bacteria have protective coats or other factors that prevent destruction, killing results from oxidizing agents formed by enzymes in the membrane These oxidizing agents include large quantities of superoxide (O2 –), hydrogen peroxide (H2O2), and hydroxyl ions (–OH–), all of which are lethal to most bacteria, even in small quantities. Also, lysosomal enzymes, myeloperoxidase , catalyzes the reaction between H2O2 and chloride ions to form hypochlorite, which is exceedingly bactericidal.

67. Monocyte -Macrophage Cell System ( Reticuloendothelial System) The total combination of monocytes,mobile , macrophages, fixed tissue macrophages, and a few specialized endothelial cells in the bone marrow, spleen, and lymph nodes is called the reticuloendothelial system. all or almost all these cells originate from monocytic stem cells; therefore, the reticuloendothelial system is almost synonymous with the monocyte -macrophage system.

68. Tissue macrophages in the skin and subcutaneous tissues  Histiocytes Macrophages ( Kupffer Cells) in the liver sinusoids

69. Inflammation: Role of Neutrophils & Macrophages Tissue macrophages is the First Line of defense against infection Neutrophil invasion of the inflamed area is a Second Line of Defense. Second Macrophage invasion into the inflamed tissue is a Third Line of Defense. Along with the invasion of neutrophils . Increased production of granulocytes and monocytes by the Bone Marrow Is a Fourth Line of Defense

70. Blood vessel Red blood cell Plasma White blood cell Platelets

71. 3. Platelets (Thrombocytes) * Cell fragments bound to megakaryocytes * “Bud Off” and are released into the blood

72. CHARACTERISTICS OF PLATELETS CHARACTERISTICS: 1. Fragment of cells 2. round cell that lacks a nucleus 3. half size of the RBC 4. life span = around 10 days Platelet count: NV 140,000 – 440,000/ cumm FUNCTION: 1. Release serotonin which contracts smooth muscle in the blood vessel reducing the flow of blood and will begin the formation of a blood clot

73. Function of Platelets Stop bleeding from a damaged vessel * Hemostasis Three Steps involved in Hemostasis 1. Vascular Spasm 2. Formation of a platelet plug 3. Blood coagulation (clotting)

74. Steps in Hemostasis Immediate constriction of blood vessel Vessel walls pressed together – become “sticky”/adherent to each other Minimize blood loss *DAMAGE TO BLOOD VESSEL LEADS TO: Vascular Spasm:

75. Steps in Hemostasis a. PLATELETS attach to exposed collagen b. Aggregation of platelets causes release of chemical mediators ( ADP, Thromboxane A 2 ) c. ADP attracts more platelets d. Thromboxane A 2 (powerful vasoconstrictor) * promotes aggregation & more ADP 2. Platelet Plug formation: (figure 11-10) Leads to formation of platelet plug !

76. Figure 11-10 (+) Feedback promotes formation of platelet Plug !

77. Final Step in Hemostasis Transformation of blood from liquid to solid Clot reinforces the plug Multiple cascade steps in clot formation Fibrinogen (plasma protein) Fibri n Thrombin Blood Coagulation (clot formation): “Clotting Cascade”

78. COMPLETE BLOOD COUNT RBC 4.5 – 6 MILLION/ cumm HEMOGLOBIN 12 – 16 gm/dl HEMATOCRIT 40 – 48 % RETICULOCYTE < 1% WBC 5,000 – 10,0000/ cumm NEUTROPHIL 54 - 62% EOSINOPHIL 1 – 3% BASOPHILS <1% LYMPHOCYTES 25 – 35% MONOCYTES 3 – 9% PLATELETS 140,000 – 440,000/ cumm

79. THANK YOU!