Physiology 3

  1. Blood
    • Only fluid tissue in the body
    • Connective tissue in which living blood cells (formed elements) are suspended in a non-living matrix (plasma)
  2. Formed elements
    • RBC or erythrocytes
    • WBC or leukocytes, bilobed nuclei
    • Platelets or thrombocytes; piece of larger cell for clotting
  3. Functions of blood
    • Delivery of oxygen to tissues
    • Transport wastes and hormones
    • Maintenance of body temp, pH, and fluid volume
    • Prevent blood loss and infection
  4. Erythrocytes
    • Have no nuclei or organelles
    • Small cells shaped like a biconcave disc to increase surface area and shortens travel distance for oxygen and carbon dioxide
  5. 97% of RBC
    • Hemoglobin
    • Carries the gasses for gas exchange; binds easily and reversibly to oxygen and can bind to CO2
  6. Hemoglobin
    • Made of a protein called globin bound to a heme group, another protein
    • Globins: alpha and beta chains
    • Heme: central disc that contains an iron atom which binds to the Oxygen to hold it
  7. How many molecules of oxygen can every hemoglobin hold?
    4 molecules

    • Every RBC carries about 1 billion molecules of oxygen 
    • Blood turns red because the oxygen oxidizes the iron
  8. RBC production
    • Blood cells are formed during hematopoiesis of stem cells
    • All formed elements arise from the same type of stem cell; maturation pathways differ each blood cell type
  9. Erythropoiesis
    • Formation of RBC's or erythrocytes
    • Begins in the yolk sac during the third week of embryonic development
  10. Sites of RBC formation
    • Initial sites are liver and spleen
    • As adults, blood is made within the bone marrow
  11. Blood stem cells differentiation
    • Lymphoblasts (antibodies and T killer cells)
    • Myeloblasts (grannular leukocyts for bone marrow)
    • Hemocytoblasts (RBC)
    • Megakaryoblasts (turn into megakaryocytes which explode for plates)
  12. Cell differentiation
    • Process controlled by growth factors (hormonal control)
    • Whatever the body needs at the time
  13. Red bone marrow
    • Becomes the primary erythropoietic tissue by seven months of fetal development and remains the primary site of RBC formation 
    • Found in the bones of axial skeleton and the proximal epiphysis of the long bones like humerus, femur, and tibia
  14. Yellow marrow
    Primarily used for storage, but can convert to red marrow if necessary
  15. Is there a time when all marrow is red?
    When you are growing all marrow is red bc you need to actively produce blood cells to sustain growth
  16. Erythropoietin (EPO)
    • Hormone that controls erythropoiesis
    • Controlled by the kidney and sustains RBC production at a basal rate (little is made/destroyed based on feedback)
    • Levels increase or decrease based on the tissues demands for oxygen
  17. Stages of RBC
    • EPO stimulates stem cells to produce Hemocytoblast -> stimulates production of 
    • Early erythroblast
    • Late erythroblast
    • Normoblast
    • Reticulocyte
    • Erythrocyte
  18. Erythroblasts
    • Ribosome-producing factories
    • Ribosomes are the proteins that are needed to make hemoglobin
  19. Normoblasts
    • Hemoglobin synthesis and accumulation occurs as these are produced
    • Should only be found in the red bone marrow
  20. When is the nucleus ejected from the normoblast?
    • When normoblasts accumulate a hemoglobin concentration about 34%
    • Its nuclear functions end and is then ejected
  21. Erythrocyte
    When the cell collapses inward and assumes the biconcave shape
  22. Process between reticulocyte and erythrocyte
    • Reticulocyte migrates out of the bone marrow into the blood
    • -Cell contains ribosomes and rough ER
  23. Last cell in RBC production that synthesizes hemoglobin
  24. Reticulocyte counts
    • Used clinically as rough index of the rate of RBC formation
    • -Entire process takes 3-5 days
    • -If you move to higher altitude, it may take more days to feel normal bc the thinner aire requires the production of RBC
  25. What happens when reticulocyte differentiates into erythrocyte?
    The cell loses its RER and ribosomes so it cannot synth hemoglobin, grow or divide
  26. Erythrocyte lifespan
    120 days

    Generally, there are about 1-2 million new erythrocytes formed each second
  27. What happens when there is hypoxia due to decreased RBC count, decreased availability of O2 in the blood, or increased tissue demands for O2?
    • Kidneys (and liver to a smaller extent) releases erythropoietin
    • EPO stimulates red bone marrow
    • Enhanced erythropoiesis increases RBC count; increasing O2 carrying ability in the blood

    Takes 1.5-2 days
  28. Regulation of erythropoiesis
    • Based on oxygen levels; monitored by chemoreceptors and the kidney can release EPO
    • Drop may be due to: hemorrhage, excess RBC destruction, high altitudes, aerobic exercise
  29. Too much or too little erythrocytes
    • Too few in circulation, tissue hypoxia may occur (oxygen deprivation)
    • Too many, makes blood too viscous or thick which causes high BP
  30. Sperocytosis
    Where the RBC are the wrong shape so your body destroys them
  31. B vitamins
    • Folic acid and B12 are essential for DNA synthesis
    • Lack of it results in fewer mitotic divisions and therefore fewer RBCs called pernicious anemia
    • Needs a sufficient amount for release of erythropoiesis with iron
  32. Pernicious anemia
    • Often due to a deficiency of intrinsic factor from the stomach which helps to absorb vitamins; w/out this you can't make DNA and therefor RBC
    • Can be seen in fetus whose mother isn't taking supplement or someone with stomach cancer that needs to be removed
  33. Iron
    • Sufficient supply needed for erythropoiesis along with B vitamins
    • Lack of iron results in decreased hemoglobin found in each RBC-- most common form called iron deficiency anemia
    • 65% of body's iron is in hemoglobin
  34. RBC destruction
    • "Die" from wear and tear from squeezing through capillaries
    • After damage, it releases chemical signals that stimulate phagocytes (macrophages) to breakdown the damaged cell
    • This occurs in the spleen "the RBC graveyard"
  35. Phagocytic process of RBC
    • Hemoglobin is first split into heme and globin
    • Heme group iron is salvaged and stored in the liver and the rest of the heme is degraded to bilirubin (yellow pigment) and is picked up by the liver and secreted into the intestines as part of bile
  36. What happens in excess RBC destruction or blockage of liver duct system
    Skin, sclera, and mucous membranes turn yellow (jaundice)
  37. Neonatal jaundice or physiological jaundice
    Occurs in newborns 3-4 days from birth

    • Fetal erythrocytes are short-lived, and break down rapidly after birth
    • Infant's liver may be unable to process the bilirubin fast enough to prevent accumulation in body tissues
    • UV light can help break down pigment
  38. Blood typing
    • Determined by the presence or absence of specific glycoproteins in the cell membrane of the RBC
    • Called antigens and the major ones for blood typing are the ABO and Rh antigens
  39. Antigens
    • or Agglutinogens
    • Glycoproteins found at the surface of RBC's plasma membrane that are highly specific and recognize each other
  40. ABO blood group antigens
    • Based on the presence of 2 antigens
    • Type A and type B which creates A, B, AB, O blood types; type O has neither of the proteins
  41. Agglutinins
    • Preformed antibodies that act against RBC's carrying ABO antigens that are not present on a person's own RBC's 
    • This means that you can be born w/antibodies, against the blood type you don't have

    Example: if you have A proteins, but not B, then you will be born with anti-B antibodies
  42. Antibodies with each blood type
    • Type AB: no antibodies
    • Type A: Anti-B antibodies
    • Type B: Anti-A antibodies
    • Type O: Anti-A and Anti-B antibodies
  43. Rh Blood Group Antigens
    • Rh agglutinogen is called Rh factor bc it was found in rhesus monkey; really Antigen D
    • 85% Americans are Rh+; which means they have the Rh antigen D with no preformed antibodies
  44. Universal donor and recipient
    • Type O-: universal donor
    • Type AB+: universal recipient
  45. Erythroblastosis Fetalis
    • If an Rh- mother carries and Rh+ fetus
    • 1st pregnancy= no problem because blood does not cross the placenta
    • However, if the mother becomes sensitized during birth meaning she is exposed to (+) blood type, then she forms anti-D antibody which attacks the blood of the 2nd Rh+ fetus
    • Common cause of miscarriage in second pregnancies

    Rhogam injections prevents formation of anti-D antibodies for subsequent pregnancies and every Rh- mother receives this injection every pregnancy
  46. Type B blood can receive what other types
    B and O
  47. Type of blood type O can receive
    O only
  48. Lab blood type testing with serum rxn
    • AB: (+) Anti-A and (+) Anti-B
    • B: (-) Anti-A and (+) Anti-B
    • A: (+) Anti-A and (-) Anti-B
    • O: (-) Anti-A and (-) Anti-B
  49. Hemostasis
    • Stoppage of bleeding
    • Fast, localized and carefully controlled response, involves blood coagulation factors normally present in plasma
  50. Three phases of hemostasis
    Vascular spasms: vasoconstriction

    Platelet plug formation

    Coagulation or blood clotting: fibrin forms a mesh
  51. Vascular spasms
    Immediate response to damage blood vessel is vasoconstriction

    • Due to:
    • Direct injury to vascular smooth muscle
    • Serotonin release by endothelial cells
    • Reflexes initiated by local pain receptors
  52. Positive biofeedback mechanism in vascular spasms
    • Increase in damage results in increase in vasoconstriction
    • This significantly reduces the blood loss
  53. Platelet plug formation
    When platelets come into contact with roughened surface such as damaged vessel

    • They then:
    • Swell and form spiked processes
    • Become sticky and adhere
    • Stimulated to release serotonin, ADP, and thromboxane A
  54. Serotonin in platelet plug formation
    Enhances vascular spasm
  55. ADP in platelet plug formation
    Potent aggregating agent that attracts more platelets to the area
  56. Thromoxane A in platelet plug formation
    Prostaglandin derivative that is generated and released to stimulate platelet aggregation and vasoconstriction
  57. Positive feedback in platelet plug formation
    Activates and attracts greater and greater numbers of platelets to the area and within 2 minute, a platelet plug is built up to reduce blood loss
  58. Petechiae
    • Small, round dark red spot caused by bleeding into the skin or beneath the mucous membrane
    • Could be due to defects in capillaries
    • Indicator of platelet deficiency if it is an often occurrence
  59. Coagulation
    • Blood clotting; blood is transformed from a liquid to a gel and is also a three phase process
    • Within plasma, there are factors that stimulate clotting process (procoagulants or coagulation factors) as well as factors that can inhibit the clotting process (anticoagulants)
    • Typically, inhibitory factors override the stimulatory ones
  60. Clotting
    Blood can be stimulated to clot after it leaks out of blood vessels into interstitial space (extrinsic mechanisms) or if it remains within the blood vessel after damage (intrinsic mechanism)
  61. Extrinsic mechanism
    • Stage 1: upon tissue damage, cells release enzyme, Tissue thromboplastin
    • Stage 2: Prothrombin Activator is an enzyme complex that stimulates the activation of the plasma protein from prothrombin into thrombin
    • Stage 3: Thrombin is the enzyme that activates the plasma protein from fibrinogen into fibrin

    Faster pathway than intrinsic
  62. What happens if tissue thromboplastin comes into contact with blood?
    It stimulates plasma protein called stuart-prower factor plus other factors to form the end product called prothrombin activator (or prothrombin converting complex- PCC)
  63. Fibrin
    Forms long protein threads that serve as meshwork to trap blood cells

    • Responsible for:
    • Structural basis of clot
    • Glue to hold platelets together
    • Can occur in 15 secs if necessary (typ. 3-6 mins)
  64. Intrinsic Mechanism
    • Stage 1: if blood comes into contact w/collagen or another foreign surface (from vessel damage) a plasma protein called hageman factor is activated; when combined with others it forms prothrombin activator or PCC
    • Stage 2: Prothrombin Activator is an enzyme complex that stimulates the activation of the plasma protein from prothrombin into thrombin
    • Stage 3: Thrombin is the enzyme that activates the plasma protein from fibrinogen into fibrin
  65. Summary of Intrinsic and Extrinsic Mechanisms
    • Prothrombin activator formed or PCC
    • Prothrombin activator converts plasma protein prothrombin into thrombin

    Thrombin catalyzes the joining of fibrinogen molecules in plasma to a fibrin mesh (traps blood and seals hole)
  66. Thrombus
    • A clot that develops and persists in an unbroken blood vessel
    • If large enough, it may block circulation and can lead to death in those tissues
    • If near the heart, death to the heart muscle may occur
  67. Embolus
    • If thrombus breaks away from vessel wall and floats freely into bloodstream and becomes embolus
    • Pulmonary emboli cannot obtain oxygen
    • Cerebral emboli causes stroke
  68. Development of clot
    • Purpose is to plug a hole to stop blood flow and prepare for site repair
    • Fibrin polymers form meshwork and forms a soft clot
    • Trapped platelets release, PDGF (platelet-derived growth factor), stimulates fibroblasts to repair the damages to wall of blood vessel
  69. Clot retraction
    Within 30-60 mins, the clot is stabilized further by this platelet-induced process 

    • Platelets produce actin filaments which contract in the same manner as muscle cells
    • As they contract, the mesh will retract bringing the edges of damaged vessel closer
    • Clot becomes firmer
    • Fluid squeezed out is serum (plasma minus proteins)
  70. Dissolution
    • Once a clot is formed, it activates this system to dissolve the clot once healing has occurred
    • Critical base step is the activation of plasma protein called plasminogen to plasmin.
    • Fibrinolysis begins within 2 days and continues over several days until clot is dissolved
  71. Plasmin
    Enzyme that digests fibrin and thus the clot
  72. Homeostatic mechanisms that prevent clots from forming or becoming unnecessarily large
    • Flow of blood
    • Structural and molecular characteristics of endothelial lining
    • Fibrin
    • Antithrombin III
    • Heparin
    • Tissue plasminogen Activator (TPA)
  73. Flow of blood
    • Clot formation in rapidly moving blood is unsuccessful bc the activated clotting factors are diluted and prevented from accumulating
    • Reason why you need to keep moving after surgery bc it prevents clots
    • Arteries need to be died off and pressure held to prevent the factors from being washed away
  74. Structural and molecular characteristics of the endothelial lining
    • As long as endothelium is smooth and intact, platelets are prevented from clinging and piling up
    • Also, prostaglandin PGI(prostacyclin) is secreted by endothelial surface cells normally prevent platelet adherence
  75. Fibrin
    • Almost all thrombin produced is absorbed or bound onto the fibrin threads so fibrin effectively acts as an anticoagulant to prevent enlargement of the clot and prevents thrombin from acting elsewhere
    • Free thrombin exerts a positive feedback mechanism
  76. Antithrombin III
    Thrombin that is not absorbed by fibrin is quickly inactivated by antithrombin III (Protein present in plasma)
  77. Heparin
    • Natural anticoagulant contained in granules of basophils and also produced by endothelial cells
    • Ordinarily secreted in small amounts into the plasma
  78. Tissue plasminogen activator (TPA)
    • Natural substance produced by genetic engineering
    • When injected directly into the heart restores blood flow quickly and puts an end to many heart attacks in progress
Card Set
Physiology 3