General physiology lecture 2


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General physiology lecture 2

  1. 1. BLOOD PHYSIOLOGY Lecture No.2
  2. 2. Main F unctions of B lood <ul><li>Transport: A giant transportation system </li></ul><ul><li>Milieu or homeostatic funtion : Organism tries to keep blood composition stable and it help s to hold interstitial environment stability </li></ul><ul><li>Defense /protection: </li></ul><ul><ul><li>3.1. Defense against blood loss or bleeding – hemostasis, blood coagulation. </li></ul></ul><ul><ul><li>3.2. Defense against foreign biological material or immunological defense </li></ul></ul><ul><ul><li>NB : To reali z e those functions blood has to be permanently circulating </li></ul></ul>
  3. 3. Body W ater <ul><li>Adult person contains ~60% of water, i.e. 70 kg weighting person 42 L </li></ul><ul><li>2/3 (~28 l) of body water is intracellular fluid ja 1/3 (~14 l) extracellular fluid </li></ul><ul><li>4/5 of extracellular fluid (~11 l) is interstitial fluid and 1/5 (~3 l ) the blood plasma </li></ul><ul><li>Extracellular fluid also contains transcellular fluids: cerebrospinal fluid (CSF), secretions of exocrine glands, etc </li></ul>
  4. 4. Body F luids <ul><li>Glandular secretions, filtrates or composites of several simultaneously running processes </li></ul><ul><li>Body fluids usually contain many components </li></ul><ul><li>Body fluids have several functions based on their component properties. </li></ul>
  5. 5. Transfer of substances between different fluid compartments <ul><li>Inside of the compartment: concentration or pressure gradient </li></ul><ul><li>Between compartments: </li></ul><ul><li>Extracellular space – cells: ordinary and osmotic diffusion </li></ul><ul><li>Blood plasma – interstitial space: diffusion and filtration (see the Starling equation by microcirculation or ultrafiltration in kidneys) </li></ul>
  6. 6. Estimation of the fluid compartment volume <ul><li>The most popular way to estimate those volumes is the dilution method, which takes into account a decrease of indicator substantce content in a new common volume. </li></ul><ul><li>D 2 O as an indicator is good to measure total body water </li></ul><ul><li>Inulin is good to measure volume of extracellular fluid compartmet, because it can penetrate capillaries but not cell membranes. </li></ul><ul><li>Evans blue or radioactive 131 I are good to measure blood plasma volume, because they do well in circulation. </li></ul>
  7. 7. Blood <ul><li>Hematolology and many other special terms </li></ul><ul><li>Blood has a holy reputation, other body fluids do not possess much importance but participates in homeostasis </li></ul><ul><li>The maintenance of a relatively constant volume and a stable composition of blood is very essential in homeostasis. </li></ul><ul><li>The total body fluid volume and the total amounts of solutes as well as their concentrations are relatively constant during steady state conditions, as required for homeostasis. </li></ul>
  8. 8. Blood C irculation
  9. 9. Blood, general features <ul><li>Fluid connective tissue, amount 7-8% of body weight, ~5 L </li></ul><ul><li>~55% of blood volume is plasma and ~45% cells </li></ul><ul><li>Blood is a temporary home for its constituents, they have different ways and mechanisms to appear and leave blood. </li></ul>
  10. 10. Physical and chemical properties of blood <ul><li>Blood volume: 4-5 liters(F); 5-6 liters (M) </li></ul><ul><li>Total blood density 1050-1060 g/L </li></ul><ul><li>Plasma density 1024-1030 g/L </li></ul><ul><li>Density of blood cells 1089-1097 g/L </li></ul><ul><li>Osmotic pressure 7 . 4 - 7 . 6 atm </li></ul><ul><li>Colloid - osmotic or oncotic pressure 25-30 mmHg 0 . 002 atm </li></ul><ul><li>Freezing temperature – 0 . 55 ° C </li></ul><ul><li>Total relative viscosity 4 . 0 - 5 .5 </li></ul><ul><li>Plasma relative viscosity ~1 . 8 </li></ul><ul><li>pH – 7.4 </li></ul><ul><li>Salinity - 0.85% - .90% </li></ul>
  11. 11. Hematocrit <ul><li>The ratio of blood cells to total blood volume </li></ul>
  12. 12. Hematocrit <ul><li>Hematocrit (PCV) is the percentage of the blood that is made up of red blood cells. </li></ul><ul><li>It is normally 40-45 vol %) </li></ul><ul><li>It is determined by centrifuging blood in a hematocrit tube (capillary tube) until the cells become tightly packed at the bottom of the tube. </li></ul><ul><li>When the hematocrit and the quantity of the hemoglobin is each respective cell are normal, the blood contains an average 15 grams of Hgb in every 100 ml. </li></ul><ul><li>Each gram of pure Hgb is capable of combining with approximately 1.39 ml of oxygen. </li></ul>
  13. 13. Composition of Blood
  14. 14. Blood P lasma <ul><li>Blood plasma is the liquid portion of clotted blood </li></ul><ul><li>90-92% water </li></ul><ul><li>6-8% plasma proteins </li></ul><ul><li>1-2% heterogenic group of low molecular weight substances </li></ul><ul><li>Because the plasma and interstitial fluids are separated only by highly permeable capillary membranes, their ionic compositions are similar. </li></ul><ul><li>The most important difference between these 2 compartments is the higher concentration of proteins in the plasma; the capillaries have a low permeability of the plasma proteins and, therefore leak only small amounts of proteins into the interstitial spaces. </li></ul>
  15. 15. Plasma P roteins <ul><li>Albumins (60%) </li></ul><ul><li>G lobulins : </li></ul><ul><li>α -, β - and γ -globulins </li></ul><ul><li>F ibrinogen (40%) </li></ul><ul><li>Electrophoresis is </li></ul><ul><li>classical method to </li></ul><ul><li>separate these proteins </li></ul>
  16. 16. Plasma Proteins <ul><li>A lbumins are homogeneous group s of proteins produced by hepatocytes with m ole c ular weight: ~70 000 D </li></ul><ul><li>Essentially all the albumin and fibrinogen of the plasma proteins as well as 50-80% of the globulins are formed in the liver. </li></ul><ul><li>Some globulins are formed in the lymphoid tissues. These are mainly the gamma globulins that constitute the antibodies. </li></ul><ul><li>A person with severe renal disease loses as much as 20 g of PP in the urine/day for months. </li></ul><ul><li>In cirrhosis of the liver, large fibrous tissue develop among hepatic cells, causing reduction of PP formation which leads decreased osmotic pressure which cause generalized edema. </li></ul>
  17. 17. The synthesis of plasma proteins <ul><li>The Rate of PP formation by the liver: extremely high at </li></ul><ul><li>30 g/day; 17 g albumins and 5 g globulins per day. </li></ul><ul><li>The half life time of albumins is 10-15 days </li></ul><ul><li>& globulins - 5 days </li></ul><ul><li>Major Functions: </li></ul><ul><li>Albumin – provide colloid osmotic pressure in the plasma, </li></ul><ul><li>which prevents plasma loss from the capillaries. </li></ul><ul><li>Globulins – perform enzymatic functions in the plasma; </li></ul><ul><li>transport (e.g. metals, lipids etc), clotting factors, </li></ul><ul><li>antibodies agains t antigens </li></ul><ul><li>Fibrinogens – polymerizes into long fibrin threads during </li></ul><ul><li>blood coagulation, thereby forming blood clots, that help repair leaks in the circulatory system </li></ul>
  18. 18. Genesis of Blood C ells
  19. 19. Pluripotential Hematopoietic Stem Cell <ul><li>The blood cells begin their lives in the bone marrow from a single type of cell called the PHSC, from which all the circulating blood cells are derived. </li></ul><ul><li>As these cells reproduce, a small portion of them remains exactly like the original PHSC and is retained in the bone marrow to maintain a supply of these, although their numbers diminish with age. </li></ul>
  20. 20. Hematopoiesis : Growth Inducers and Differentiation Inducers
  21. 21. Genesis of Blood Cells <ul><li>From the bone marow cells – it is the PHSCs (pluripotential hemopoietic stem cells) – from which all cells of the circulating blood are derived </li></ul><ul><li>Growth and reproduction of the different stem cells are controlled by multiple proteins </li></ul><ul><li>Interleukin-3, differentiation inducers, other growth inducers </li></ul>
  22. 22. Main P rinciples of H em o p o iesis <ul><li>All cells are originated from the pluripotent hemopoietic stem cells in the red bone marrow . </li></ul><ul><li>Only mature blood cells can reach circulation </li></ul><ul><li>When level of cell diffrentiation is higher, then their ability for mitosis is less. </li></ul><ul><li>Mature blood cells are not able to divide </li></ul><ul><li>Hemopoiesis needs very careful regulation to keep numbers of cells on stable level. It means that production and death of cells must be balanced. </li></ul>
  23. 23. Growth & Differentiation inducers <ul><li>Growth and reproduction of the different stem cells are controlled by multiple proteins called growth inducers </li></ul><ul><li>Four major growth inducers: </li></ul><ul><li>1. Interleukin-3 – promotes growth and reproduction </li></ul><ul><li>of virtually all the different types of committed </li></ul><ul><li>stem cells </li></ul><ul><li>2. Interleukin 5 & 6 – induce growth of only specific </li></ul><ul><li>types of cells </li></ul><ul><li>4. Differentiation inducers – promotes differentiation </li></ul><ul><li>of committed stem cells into final adult blood </li></ul><ul><li>cell </li></ul>
  24. 24. Hematopoiesis and Diapedesis
  26. 26. The Role of Erythropoietin <ul><li>Erythropoietin is a circulating hormone and is the principal factor that stimulates rbc production </li></ul><ul><li>It is a glycoprotein, with a molecular weight of 34,000 </li></ul><ul><li>90% is produced by the kidney and 10% by the liver </li></ul><ul><li>When both kidneys are removed from a person or are destroyed by renal failure, the person becomes very anemic because the 10% of normal ETO formed in other tissues (mainly in the liver) is sufficient to cause only 1/3 to ½ the red cell formation needed by the body. </li></ul>
  27. 27. Maturation of RBC <ul><li>Especially important for final maturation of rbc’s are 2 vitamins: Vitamin B12 and folic acid </li></ul><ul><li>Both are essential for the synthesis of DNA; each in a different way is required for the formation of TTP </li></ul><ul><li>Therefore, lack of either B12 or folic acid causes diminished DNA and consequently failure of nuclear maturation and division </li></ul><ul><li>Furthermore, this will also cause the bone marrow to produce macrocytes; cells with flimsy membranes, often irregular, large, oval instead of the usual biconcave shape </li></ul>
  28. 28. <ul><li>Apoptosis or programmed cell death is a normal physiological form of cell death that plays a key role both in the maintenance of adult tissues and in embryonic development. </li></ul><ul><li>In adults, programmed cell death is responsible for balancing cell proliferation and maintaining constant cell numbers in tissues undergoing cell turnover. </li></ul><ul><li>For example, about 5 × 10 11 blood cells are eliminated by programmed cell death daily in humans, balancing their continual production in the bone marrow. </li></ul>
  29. 29. Red blood cells or erythrocytes <ul><li>Number is 4-5X10 12 per liter </li></ul><ul><li>Without nuclei, ~1/3 of mass is hemoglobin </li></ul><ul><li>Main function is to carry oxygen </li></ul><ul><li>Clinically important are blood groups – ABO and Rh systems </li></ul>
  30. 30. Erythrocytes
  31. 31. Hemoglobin <ul><li>Content in men 130-160 g/l, in women 120-160 g/l </li></ul><ul><li>The Hb molecul e contains 4 subunits, everyone with heme and globin </li></ul><ul><li>Each chain has 4 iron atoms that bind loosely w/ 1 molecule of O 2 </li></ul><ul><li>Synthesis of hemoglobin begins in the proerythroblasts and continues until a few days after the cells leave the bone marrow and pass into the blood stream </li></ul>
  32. 32. H emoglobin
  33. 33. Formation of Hemoglobin <ul><li>First start with the formation of heme which contains 1 atom of Fe </li></ul><ul><li>Next, each heme molecule combines with a long polypeptide chain, called the globin, forming a subunit of hemoglobin </li></ul><ul><li>Each of these chains has a molecular weight of 16,000; 4 of them in turn bind together loosely to form the whole hemoglobin </li></ul>
  34. 34. H eme
  35. 35. Anemia & Polycythemia <ul><li>Anemia – deficiency of Hgb or few RBCs in the blood. </li></ul><ul><li>Types of Anemia are: </li></ul><ul><li>Blood loss anemia - after rapid hemorrhage </li></ul><ul><li>Aplastic anemia - lack of functioning bone marrow </li></ul><ul><li>Hemolytic anemia - due to fragile cells that rupture easily </li></ul><ul><li>Megaloblastic anemia-due to loss of any of Vitamin B12, folic acid and intrinsic factor from the stomach mucosa </li></ul><ul><li>Polycythemia – large quantities of extra RBCs </li></ul><ul><li>Types: Secondary or Physiologic polycythemia – seen in those who lives in higher altitudes </li></ul><ul><li>Polycythemia vera - excess production of blood cells(rbc, wbc and platelets, hematocrit & blood volume) </li></ul>
  36. 36. Which of the 3 factors cause the type of anemia?
  37. 37. What happens in Sickle cell Anemia? <ul><li>Abnormalities of the chains can alter the physical characteristics of the Hgb. In sickle cell anemia, the AA VAL is substituted for GLU at one point in each of the 2 beta chains. </li></ul><ul><li>When this type of Hgb is exposed to low O 2 it forms elongated crystals inside the RBCs about 15 um in length. </li></ul><ul><li>These make it almost impossible for the cells to pass through many small capillaries, and the spiked ends of the crystals are likely to rupture the cell membranes leading to sickle cell anemia </li></ul>
  38. 38. The ABO B lood G roups
  39. 40. Rhesus (Rh) S ystem <ul><li>A person is Rh + (~85%) when he or she has on erythocytes D antigen, otherwise they are Rh -. </li></ul><ul><li>Initially plasma doesn’t have antibodies. </li></ul><ul><li>Anti D antibodies are produced during sensibilization when D antigens reach Rh - organism </li></ul><ul><li>The R h system is important by haemotransfusion and mother-fetus Rh conflict or erythroblastosis fetalis </li></ul>
  40. 41. White blood cells or L eu k ocytes <ul><li>Normal amount is 4-10 x 10 5 WBCs in 1 L blood. </li></ul><ul><li>Main function immunological defense by: </li></ul><ul><li>1. actually destroying invading bacteria or viruses </li></ul><ul><li>2. forming antibodies and sensitized lymphocytes </li></ul><ul><li>Heterogenous group of cells and exceptionally big number of WBCs are outside of circulation where they are needed </li></ul><ul><li>The real value of WBC is that most of them are specifically transported to areas of serious infection and inflammation, thereby providing a rapid or potent defense against infectious agents. </li></ul>
  41. 42. Types of Leukocytes <ul><li>Blood provides a medium for the maintenance of homeostasis in the cell’s environment . </li></ul><ul><li>Blood functions as transport system for nutrients and gases to the cells and removing waste products and CO 2 the interstitial fluid around the cells. </li></ul><ul><li>Blood serves to link the various organs of the body, integrating them through the action of hormones </li></ul>
  42. 43. Leu k ocyte F ormula (Schilling’s Hemogram) <ul><li>Concentrations of the Different WBCs in the Blood: </li></ul><ul><li>Granulocytes </li></ul><ul><li>Neutrophilic granulocytes 50-70% </li></ul><ul><li>Eosinophilic granulocytes 2-4% </li></ul><ul><li>Basophilic granulocytes 0 . 5-1% </li></ul><ul><li>B. Agranulocytes </li></ul><ul><li>Lymphocytes 25-40% (T- and B- lymphocytes) </li></ul><ul><li>Monocytes 4-8% </li></ul>
  43. 44. Leu k ocytes
  44. 45. Classification of immunological defense mechanisms <ul><li>Unspecific mechanisms: </li></ul><ul><li>- humoral mechanisms: the complement </li></ul><ul><li>system - cellular mechanisms: phagocytosis, very </li></ul><ul><li>potent phagocytotic potential have </li></ul><ul><li>neutrophils and monocytes </li></ul><ul><li>Specific mechanisms: - humoral mechanisms: antibodies from </li></ul><ul><li>plasma cells, antigene-antibody reaction - cellular mechanisms: cytotoxic effect of T- </li></ul><ul><li>lymphocytes </li></ul>
  45. 46. Neutrophils and Macrophages <ul><li>Neutrophils and macrophages – mainly attack and destroy invading bacteria, viruses and other injurious agents. </li></ul><ul><li>How do they do these? </li></ul><ul><li>They enter the tissue spaces by diapedesis </li></ul><ul><li>They move through tissue spaces by ameboid motion </li></ul><ul><li>They are attracted to inflamed tissue areas by chemotaxis </li></ul>
  46. 47. Inflammation: Role of Neutrophils and Macrophages <ul><li>When tissue injury occurs, whether caused by bacteria, trauma, chemical, heat, or any other phenomenon, multiple substances are released by the injured tissues and cause dramatic changes in the surrounding uninjured tissues. This entire complex of tissue changes is called inflammation. </li></ul><ul><li>Inflammation is characterized by: </li></ul><ul><li>(1) Vasodilation of the local blood vessels with increased blood flow; (2)increased permeability of the capillaries allowing leakage of large quantities of liquid; (3) clotting of the fluid in the interstitial spaces; (4) migration of large numbers of granulocytes and monocytes; and (5) swelling of the tissue cells </li></ul>
  47. 48. What is the “walling-off” effect of inflammation? <ul><li>One of the first results of inflammation is to “wall-off’ the area of injury from the remaining tissues. The tissue spaces and the lymphatics in the inflamed area are blocked by fibrinogen clots so that after a while, fluid barely flows through the spaces. </li></ul><ul><li>This walling-off process delays the spread of bacteria or toxic products. </li></ul>
  48. 49. Next Meeting <ul><li>Quiz on Blood Physiology (Guyton & Hall) </li></ul><ul><li>(pp. 419-428 – Red Blood cells, Anemia & polycythemia </li></ul><ul><li>pp. 429-437 – Leukocytes, Resistance to Infection, & Inflammation </li></ul><ul><li>pp. 451-455-Blood Groups/Transfusion </li></ul><ul><li>Assignment: Immunity </li></ul>