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Lec.1.Blood,2018.pptx

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Lec.1.Blood,2018.pptx

  1. 1. The Cardiovascular System: The Blood Lec.1
  2. 2. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Blood Physiology  The cardiovascular system consists of three interrelated components:  Blood,  The heart  Blood vessels  Blood is a highly differentiated, complex living tissue that pulsates through the arteries to every part of the body, interacts with individual cells via an extensive capillary network, and returns to the heart through the venous system.  Many of the functions of blood are undertaken in the capillaries, allowing the efficient diffusion and transport across the monolayer of endothelial cells that form the thin capillary walls.
  3. 3. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Physical Characteristics of Blood  Blood is denser and more viscous (thicker) than water and slightly sticky.  The temperature of blood is 38°C (100.4°F), about 1°C higher than oral or rectal body temperature  pH ranging from 7.35 to 7.45.  The color of blood varies with its O+2 content. When saturated with oxygen, it is bright red. When unsaturated with O+2, it is dark red.  Blood constitutes about 20% of extracellular fluid, amounting to 8% of the total body mass.  The blood volume is 5 to 6 liters in adult male and 4 to 5 liters in adult female.  The gender difference in volume is due to differences in body size.
  4. 4. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. The general Functions of blood Blood has three general functions: • Transportation  Blood transports O+2 from the lungs to the cells of the body and carbon dioxide from the body cells to the lungs for exhalation.  It carries nutrients from the gastrointestinal tract to body cells and  hormones from endocrine glands to other body cells.  Blood also transports heat and waste products to various organs for elimination from the body. • Regulation  Circulating blood helps maintain homeostasis of all body fluids.  Blood helps regulate pH through the use of buffers.
  5. 5. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  It helps adjust body temperature through the heat absorbing and coolant properties of the water in blood plasma and its variable rate of flow through the skin, where excess heat can be lost from the blood to the environment.  Protection  Blood can clot, which protects against its excessive loss from the cardiovascular system after an injury.  its white blood cells protect against disease by carrying on phagocytosis.  Several types of blood proteins, including antibodies, interferons, and complement, help protect against disease in a variety of ways.
  6. 6. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Whole blood has two components: 1. The yellow upper layer is plasma, the liquid portion of blood, which accounts for about 55% of the total volume of whole blood. 2. The lower layer consists of the formed elements normally constitute about 45% of the total volume of whole blood.  If a sample of blood is centrifuged (spun) in a small glass tube, the cells (which are more dense) sink to the bottom of the tube  while the plasma (which is less dense) forms a layer on top. Composition of blood Components of blood
  7. 7. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  The plasma is a complex solution and suspension of chemical substances.  It consists of about 90% water, 1% inorganic substances, 6-8% proteins, with the remainder glucose, amino acids, lipids, nitrogenous wastes of metabolism (e.g. urea),  gases, enzymes, hormones and other substances.  The water of plasma serves in transport functions and  the inorganic substances act as buffers and osmotically active particles and ensure proper excitability of cells. The plasma
  8. 8. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  The plasma proteins are so named because they usually remain in the plasma, and maintain oncotic pressure which helps to keep the blood volume constant.  The three major types of plasma proteins are  Albumins (54% of plasma proteins),  globulins (38%)  fibrinogen (7%).  Most plasma proteins are made in the liver.  An exception is the antibodies or immunoglobulin produced by B- lymphocytes, which function in immunity.  The primary sign of plasma protein deficiency is development of edema because water filtered from blood vessels and is not osmotically return to the capillaries. The plasma proteins
  9. 9. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  The percentage of total blood volume occupied by RBCs is called the hematocrit.  A hematocrit of 40 indicates that 40% of the volume of blood is composed of RBCs.  The normal range of hematocrit for adult females is 38–46% (average 42); for adult males, it is 40–54% (average 47).  The hormone testosterone, present in much higher conce. in males than in females, stimulates synthesis of erythropoietin (EPO), the hormone that in turn stimulates production of RBCs.  Thus, testosterone contributes to higher hematocrits in males.  A significant drop in hematocrit indicates anemia. Hematocrit
  10. 10. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  In polycythemia the percentage of RBCs is abnormally high, and the hematocrit may be 65% or higher.  The formed elements  Blood cells include erythrocytes (red blood cells),  leukocytes (white blood cells),  blood thrombocytes (platelets)  RBCs and WBCs are whole cells
  11. 11. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Regulation of Blood Cell Production  The process of blood cell generation, hematopoiesis, occurs in healthy adults only in the bone marrow.  Extramedullary hematopoiesis (e.g., the generation of blood cells in the spleen) is observed only in some disease states, such as leukemia.  Hematopoietic cells are also found in the blood of adults, but in extremely low numbers.  Large numbers of hematopoietic cells can be recovered from aspirates of the iliac crest, sternum, pelvic bones, long bones, and ribs of adults.  Within the bones, hematopoietic cells germinate in extravascular sinuses, called marrow stroma. stromal cells, are differentiating cells found in abundance within bone marrow. The most common stromal cells include fibroblasts and pericytes.
  12. 12. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  All blood cells are production begins with the proliferation of pluripotent hematopoietic stem cells (uncommitted) in red bone marrow,  A single population of bone marrow cells, which are undifferentiated cells  capable to produce two further types of stem cells, which have the capacity to develop into several types of cells.  These stem cells are called myeloid stem cells and lymphoid stem cells.  Myeloid stem cells give rise to red blood cells, platelets, monocytes, neutrophils, eosinophils, and basophils.
  13. 13. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  Lymphoid stem cells begin their development in red bone marrow but complete it in lymphatic tissues; they give rise to lymphocytes.  During hemopoiesis, some of the myeloid stem cells differentiate into progenitor cells.  Other myeloid stem cells and the lymphoid stem cells develop directly into precursor cells.  Progenitor cells are no longer capable of reproducing themselves and are committed to giving rise to more specific elements of blood.  Some progenitor cells are known as colony-forming units (CFUs).  Following the CFU designation is an abbreviation that indicates the mature elements in blood that they will produce:
  14. 14. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  CFU-E ultimately produces erythrocytes;  CFU-Meg produces megakaryocytes, the source of platelets;  CFU-GM ultimately produces granulocytes (specifically, neutrophils) and monocytes.  In the next generation, the cells are called precursor cells, also known as blasts.  Over several cell divisions they develop into the actual formed elements of blood.  For example, monoblasts develop into monocytes,  Eosinophilic myeloblasts develop into eosinophils.  Several hormones called hemopoietic growth factors regulate the differentiation and proliferation of particular progenitor cells.
  15. 15. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  Erythropoietin increases the number of RBCs precursors and produced primarily by cells in the kidneys that lie between the kidney tubules (peritubular interstitial cells).  Thrombopoietin is a hormone produced by the liver that stimulates the formation of platelets from megakaryocytes.  Several different cytokines regulate development of different blood cell types.  Two important families of cytokines that stimulate white blood cell formation are:  Colony-stimulating factors (CSFs) and  Interleukins.
  16. 16. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
  17. 17. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. The Erythrocyte  Mature erythrocyte is disc biconcave,  Non nucleated and flexible.  Disc averaging 7.8-8 µm in diameter, 2 µm thick at their edges and 1 µm thick at their center.  The shape disc biconcave provides the maximum surface area to give the greatest possible surface for diffusion of gasses.  The erythrocyte maintains its shape by virtue of its complex membrane skeleton, which consists of an insoluble mesh of fibrous proteins attached to the inside of the plasma membrane.  This structural arrangement allows the erythrocyte great flexibility as the cell twists and turns through small, curved vessels.
  18. 18. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  In addition to structural proteins of the membrane, several functional proteins are found in the cytoplasm of erythrocytes.  These include haemoglobin,  Antioxidant enzymes, and  Glycolytic systems to provide cellular energy (ATP).  The plasma membrane possesses ion pumps that maintain a high level of intracellular K+ and a low level of intracellular Ca+2 and Na+.  RBCs does not contain nucleus, to consume small amounts of O2, glucose and ATP, and  Produce small quantities of CO2.  Because mature RBCs have no nucleus, all their internal space is available for O2 transport.
  19. 19. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  Because RBCs lack mitochondria and generate ATP anaerobically, they do not use up any of the O2 they transport.  A healthy adult male has about 5.4 million RBCs per microliter of blood,  A healthy adult female has about 4.8 million.  To maintain normal numbers of RBCs, new mature cells must enter the circulation at the astonishing rate of at least 2 million per second, a pace that balances the equally high rate of RBC destruction.  The red, oxygen-transporting protein of erythrocytes consists of  A globin (or protein) portion and  Four heme groups, the iron-carrying portion.
  20. 20. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hemoglobin  This complex protein possesses four polypeptide chains: two α -globin molecules of 141 amino acids each and two molecules of another type of globin chain (β, γ, Δ, £), each containing 146 amino acid residues.  Four types of hemoglobin molecules can be found in human erythrocytes:  embryonic, fetal, and two different types found in adults (HbA, HbA2).  Each hemoglobin molecule is designated by its polypeptide composition.  For example, the most prevalent adult hemoglobin, HbA, consists of two α chains and two β chains.  Its formula is given as α2β2.
  21. 21. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. RBC shape and Structure of hemoglobin A. Each molecule of hemoglobin possesses four polypeptide chains, each containing iron bound to its heme group
  22. 22. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  HbA2, which makes up about 1.5 to 3% of total haemoglobin in an adult, has the subunit formula (α2Δ2).  Fetal haemoglobin (α2γ2) is the major hemoglobin component during intrauterine life.  Its levels in circulating blood cells decrease rapidly during infancy and reach a conce. of 0.5% in adults.  Embryonic hemoglobin is found earlier in development. It consists of (α2£2), the production of £ chains ceases at about the third month of fetal development.  Sickle-cell anemia, for example, results from the presence of sickle- cell haemoglobin (HbS), which differs from normal adult HbA because of the substitution of a single amino acid in each of the two β chains.
  23. 23. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  In normal people, the percentage of Hb in RBCs is always near the maximum value.  The heme portion of Hb is synthesized in mitochondria and the protein part (globin) is synthesized in ribosomes.  However, when Hb formation is deficient in the bone marrow,  The percentage of Hb in these cells may lower below normal value  The volume of RBCs decrease because of diminished Hb to fill the cell.  When the hematocrit value or packed cell volume (is the volume of red cells expressed as percentage of total volume of blood- normally=40-45%), and The quantity of Hb in each cells are normal, Quantity of Hemoglobin in RBCs
  24. 24. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  The whole blood of men contains about 16gm Hb/(dl) of blood  In women contain about 14gm Hb/(dl) of blood. and  Each gram of pure Hb is able to combine with about 1.39 milliliters of oxygen.  Each RBC contains about 280 million hemoglobin molecules.
  25. 25. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Regulation of RBCs production  Tissue oxygenation consider as the basic regular of RBCs production so that, any condition that causes decrease in the quantity of O+2 transported to the tissue ordinarily increases the rate of RBCs production. such as:  Low blood volume, anemia, low Hb,  Poor blood flow-cardiac failure,  Pulmonary disease  Hemorrhage  Thus when a person becomes extremely anemic as a result of hemorrhage or other conditions, the bone marrow immediately begins to produce large quantities of RBCs.
  26. 26. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  At high altitudes, where the quantity of O+2 in the air is greatly decreased and insufficient O+2 is transported to the tissues and RBCs production is considerably increased.  The principal factor that stimulates RBCs production and maturation is a circulating hormone called erythropoietin and its formation in response to hypoxia (cellular O+2 deficiency) and  This hormone enhances RBCs production until hypoxia is relieved.  In normal person, about 90% of all erythropoietin is formed in the kidney and the remainder is formed mainly in the liver.  So that, in kidney failure, the person becomes very anemic, because 10% of erythropoietin that is formed mainly in the liver is not sufficient to cause formation of RBCs as needed in the body.
  27. 27. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Fig.4.Action of erythropoietin.
  28. 28. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  When RBCs are delivered from bone marrow to the circulation, they normally circulate an average of about 120 day before being destroyed.  Because of the wear and tear their plasma membranes undergo as they squeeze through blood capillaries.  Without a nucleus and other organelles, RBCs cannot synthesize new components to replace damaged ones.  The plasma membrane becomes more fragile with age, and the cells are more likely to burst, especially as they squeeze through narrow channels in the spleen.  Some of the senescent (old) red cells break up in the bloodstream, but the majority is engulfed by macrophages by the monocyte- macrophage system, Destruction of RBCs
  29. 29. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  The breakdown products are recycled and used in numerous metabolic processes, including the formation of new red blood cells.  The recycling occurs as follows: ● Macrophages in the spleen, liver, or red bone marrow phagocytize ruptured and worn-out red blood cells. ● The globin and heme portions of hemoglobin are split apart. ● Globin is broken down into amino acids, which can be reused to synthesize other. ● Iron is removed from the heme portion in the form of Fe3+, which associates with the plasma protein transferrin, a transporter for Fe3+ in the bloodstream.
  30. 30. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ● In muscle fibers, liver cells, and macrophages of the spleen and liver, Fe3+ detaches from transferrin and attaches to an iron-storage protein called ferritin. ● On release from a storage site or absorption from the gastrointestinal tract, Fe3+ reattaches to transferrin. ● The Fe3+-transferrin complex is then carried to red bone marrow, where RBC precursor cells take it up through receptor mediated endocytosis for use in hemoglobin synthesis. • Iron is needed for the heme portion of the hemoglobin molecule, • and amino acids are needed for the globin portion. • Vitamin B12 is also needed for the synthesis of hemoglobin.
  31. 31. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ● Erythropoiesis in red bone marrow results in the production of RBCs, which enter the circulation. ● When iron is removed from heme, the non-iron portion of heme is converted to biliverdin, a green pigment, and ● Then into bilirubin, a yellow orange pigment. ● Bilirubin enters the blood and is transported to the liver. ● Within the liver, bilirubin is released by liver cells into bile, which passes into the small intestine and then into the large intestine. ● In the large intestine, bacteria convert bilirubin into urobilinogen.
  32. 32. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ● Some urobilinogen is absorbed back into the blood, converted to a yellow pigment called urobilin, and excreted in urine. ● Most urobilinogen is eliminated in feces in the form of a brown pigment called stercobilin, which gives feces its characteristic color.
  33. 33. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
  34. 34. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Reactions of Hemoglobin  Hemoglobin binds O+2 to form oxyhemoglobin, O+2 attaching to the Fe2+ in the heme.  The affinity of hemoglobin for O+2 is affected by:  PH,  Temperature  The conce. in the red cells of 2,3-biphosphoglycerate (2,3-BPG).  These factors decreasing the affinity of hemoglobin for O+2.  When blood is exposed to various drugs and other oxidizing agents in vitro or in vivo, the ferrous iron (Fe2+) molecule is converted to ferric iron (Fe3+), forming methemoglobin.
  35. 35. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  Methemoglobin is dark-colored, and when it is present in large quantities in the circulation, it causes a dusky discoloration of the skin resembling cyanosis.  Carbon monoxide reacts with hemoglobin to form carbon monoxyhemoglobin (carboxyhemoglobin).  Heme is a part of the structure of myoglobin, an oxygen-binding pigment found in red muscles.  Neuroglobin, an oxygen-binding globin, is found in the brain.

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