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Bone marrow blood comp. (8)


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Bone marrow blood comp. (8)

  1. 1. Lecture Title Blood Components Drs. Brenner and Chris Reilly Block 2 Physiology
  2. 2. Bone Marrow and Blood Components• Describe production of RBC’s in regard to what tissues and what times in life they are produced• State normal and abnormal Hemocrit. Detail possible genetic, pathophysiolgic disturbances that lead to abnormal RBC production• Define the normal range for each of the following and state what a abnormal elevated or reduced value may indicate – Hemoglobin; – Red Blood Cell (RBC) Count; – White Blood Cell (WBC) Count; – White Blood Cell Differential Count – platelet Count – Reticulocyte Count
  3. 3. Blood Percentages• 55 % plasma – Plasma is the straw-colored liquid in which the blood cells are suspended.• 45 % formed elements – Red blood cells (Erythrocytes) – White blood cells (leukocytes) – Platelets (thrombocytes)
  4. 4. Blood Components
  5. 5. Red blood cells (erythrocytes) • Red blood cells are biconcave discs erythrocytes
  6. 6. Red Blood Cells• Red cells, or erythrocytes , are relatively large microscopic cells without nuclei.• Red cells normally make up 40-50% of the total blood volume.• They transport oxygen from the lungs to all of the living tissues of the body and carry away carbon dioxide.• The red cells are produced continuously in our bone marrow from stem cells at a rate of about 2-3 million cells per second.
  7. 7. Erythrocyte→7.5µm in dia• Anucleate- so cant reproduce; however, repro in red bone marrow• Hematopoiesis- production of RBC• Function- transport respiratory gases• Hemoglobin- quaternary structure, 2 α chains and 2 β chains• Lack mitochondria. Why?• 1 RBC contains 280 million hemoglobin molecules• Men- 5 million cells/mm3• Women- 4.5 million cells/mm3• Life span 100-120 days and then destroyed in spleen (RBC graveyard)
  8. 8. Red Blood Cells• Hemoglobin is the gas transporting protein molecule that makes up 95% of a red cell.• Each red cell has about 270,000,000 iron-rich hemoglobin molecules. – People who are anemic generally have a deficiency in red cells.• The red color of blood is primarily due to oxygenated red cells.
  9. 9. Hemoglobin
  10. 10. CBC with Differential/ Platelet White Blood Cells• Red Blood Cell count • Neutrophils• White Blood Cell count • Neutrophils, absolute• Platelet count • Lymphocytes• Hemoglobin • Monocytes• Hematocrit • Eosinophils• Red Blood cell distribution width • Basophils (RDW) • Lymphocytes, absolute• Mean Cell Volume (MCV) • Monocytes, absolute• Mean Cell Hemoglobin (MCH) • Eosinphils, absolute• Mean Corpuscular Hemoglobin • Basophils, absolute Concentration (MCHC)
  11. 11. CarolBrenner11/5/12 RDW RDW: Red Blood Cell Distribution Width, normal RBC width 6-8 μm. Calculated by (standard deviation of MCV/mean MCV) x 100 Normal range: 11-15% Used with MCV to determine type of anemia Iron Deficiency Anemia: high RDW, low MCV Folate and Vitamin B12 Deficiency anemia: high RDW, high MCV
  12. 12. Mean Corpuscular VolumeMCV: Mean Corpuscular Volume-measureof the # events countedaverage RBC size (calculated by(Hct/#RBCs)x 10)Normal range is 80-99 femtoL increased in pernicious anemia(150 fL) and alcoholism allows differentiation between a microcytic anemia and anormocytic anemia RBC Volume 
  13. 13. Mean Corpuscular HemoglobinMCH: Mean Corpuscular Hemoglobin—average mass of Hb/RBC (calculated bytotal mass of Hb/total # RBCs in a volume blood) normal range = 27-31 pg/cell MCH is reduced in hypochromic anemias
  14. 14. Definitions:MCH: Mean Corpuscular Hemoglobin—average mass of Hb/RBC (calculated bytotal mass of Hb/total # RBCs in a volume blood) normal range = 27-31 pg/cell MCH is reduced in hypochromic anemiasMCHC: Mean Corpuscular Hemoglobin Concentration- a measure of theamount of hemoglobin in a given volume of packed RBCs (calculated by Hb/Hct) reference range= 32-36 g/dL or 4.9-5.5 mmol/L elevated in sickle cell disease, hereditary sperocytosis, homozygous hemoglobin C disease reduced in microcytic anemias normal in macrocytic anemias
  15. 15. Complete Blood Count (Hct)Hematocrit-% of packed RBC volumelow HctAnemiahigh Hct Polycythemia(more RBCs that normal
  16. 16. Polycythemia VeraWhat is it?Bone marrow disease that leads to an abnormal increase in number of blood cells(primarily RBCs, although platelets and WBCs can also increase)Rare disease occurring more often in men than womenLinked to a gene mutation: JAK2V617FSymptoms: dizziness, breathing difficulty when prone, enlarged spleen,headache blood clottingTests: complete CBC with differential, erythropoietin level, bone marrow biopsyand complete metabolic panelTreatment: Goal to prevent clotting, weekly phlebotomy until Hct comes below50%
  17. 17. HemoglobinHb is a protein in RBC that binds O2in lungs and delivers it to peripheral tissuesto maintain the cell’s metabolic activities andViabilityOne diabetes mellitus Type 2 test is:HbA1cGlucose in blood “sticks” to hemoglobin tomakeglycosylated Hb  HbA1cMore glucose in blood the higher the value forHbA1c
  18. 18. Reticulocyte CountThis is a marker of effective erythropoiesisReticulocytes are immature RBCs typicallycomposing 1% of the RBCs in the body.reticulocytes develop and mature in the redbone marrow and then circulate in the bloodstream for about a day before maturing to RBCReticulocytes have no nucleus but do show areticular network (mesh-like) of rRNA thatBecomes visible under a mciroscope whenStaoned with new methylene blue.. Blood smear from a patient with hemolytic anemia
  19. 19. Red Blood Cell DiseasesAnemia- when blood has low O2 carrying capacity;insufficient RBC or iron deficiency.Factors that can cause anemia- exercise, B12deficiencyPolycythemia- excess of erythrocytes, ↑ viscosity ofblood;8-11 million cells/mm3Usually caused by cancer, tissue hypoxia, dehydration;however, naturally occurs at high elevationsBlood doping- in athletes→remove blood 2 daysbefore event and then replace it; Epoetin;- banned byOlympics.
  20. 20. Red Blood Cell DiseasesSickle-cell anemia-HbS results from a change in just one of the287 amino acids in the β chain in the globinmolecule.Found in 1 out of 400 African Americans.Abnormal hemoglobin crystalizes when O2content of blood is low, causing RBCs tobecome sickle-shaped.Homozygous for sickle-cell is deadly, but inmalaria infested countries, the heterozygous
  21. 21. Genetics of Sickle Cell Anemia Genetics of Sickle Cell Anemia
  22. 22. Platelets (thrombocytes)Platelets
  23. 23. Platelets• Platelets or thrombocytes—clear cell fragments derived from fragmentation of precursor megakaryocytes• Life span 7-9 days• Natural source of growth factors (PDGF, TGF-β) for repair and regeneration of connective tissue• Hemostasis  blood clotting• Normal platelet count: 150,000-450,000 µL of bloodHigh platelet count= clotting (thrombosis)Low platelet count=heparin-inducedthrombocytopenia(HIT)
  24. 24. Platelets WBC RBC Platelets clumping in a blood smear PlateletPlatelet activation initiates the arachidonic acid pathway to producethromboxane 2 (TXA2)TXA2 is involved in activating other platelets and its formation in inhibites byCOX inhibitors  such as aspirin
  25. 25. Platelets• Platelets , or thrombocytes , are cell fragments without nuclei that work with blood clotting chemicals at the site of wounds. – They do this by adhering to the walls of blood vessels, thereby plugging the rupture in the vascular wall. They also can release coagulating chemicals which cause clots to form in the blood that can plug up narrowed blood vessels.• There are more than a dozen types of blood clotting factors and platelets that need to interact in the blood clotting process.
  26. 26. Hemostasis- stoppage of Platelets: 250,000-500,000 cells/mm3
  27. 27. Hemostasis- stoppage of Platelets: 250,000-500,000 cells/mm3 Tissue Damage
  28. 28. Hemostasis- stoppage of Platelets: 250,000-500,000 cells/mm3 Tissue Damage Platelet Plug
  29. 29. Hemostasis- stoppage of Platelets: 250,000-500,000 cells/mm3 Tissue Damage Platelet Plug Clotting Factors
  30. 30. Hemostasis1. Vessel injury2. Vascular spasm3. Platelet plug formation4. Coagulation
  31. 31. Platlets• Recent research has shown that platelets help fight infections by releasing proteins that kill invading bacteria and some other microorganisms. – In addition, platelets stimulate the immune system.• Individual platelets are about 1/3 the size of red cells.• They have a lifespan of 9-10 days.• Like the red and white blood cells, platelets are produced in bone marrow from stem cells.
  32. 32. Disorders of Hemostasis• Thromboembolytic disorders: undesirable clot formation• Bleeding disorders: abnormalities that prevent normal clot formation
  33. 33. Thromboembolytic Conditions• Thrombus: clot that develops and persists in an unbroken blood vessel – May block circulation, leading to tissue death• Embolus: a thrombus freely floating in the blood stream – Pulmonary emboli impair the ability of the body to obtain oxygen – Cerebral emboli can cause strokes
  34. 34. Bleeding DisordersThrombocytosis- too many platelets due to inflammation, infection or cancerThrombocytopenia- too few platelets• causes spontaneous bleeding• due to suppression or destruction of bone marrow (e.g., malignancy, radiation) – Platelet count <50,000/mm3 is diagnostic – Treated with transfusion of concentrated platelets 
  35. 35. Bleeding Disorders• Hemophilias include several similar hereditary bleeding disorders• Symptoms include prolonged bleeding, especially into joint cavities• Treated with plasma transfusions and injection of missing factors
  36. 36. Hemophilia-sex linked
  37. 37. White Blood Cell
  38. 38. White Blood Cells• White cells, or leukocytes , exist in variable numbers and types but make up a very small part of bloods volume-- normally only about 1% in healthy people.• Leukocytes are not limited to blood. – They occur elsewhere in the body as well, most notably in the spleen, liver, and lymph glands.• Most are produced in our bone marrow from the same kind of stem cells that produce red blood cells and others are produced in the thymus gland, which is at the base of the neck.
  39. 39. White Blood Cells• Some white cells (called lymphocytes ) are the first responders for our immune system. – They seek out, identify, and bind to alien protein on bacteria, viruses, and fungi so that they can be removed. – Other white cells (called granulocytes and macrophages ) then arrive to surround and destroy the alien cells.
  40. 40. White Blood Cells• They also have the function of getting rid of dead or dying blood cells as well as foreign matter such as dust.• Individual white cells usually only last 18-36 hours before they also are removed, though some types live as much as a year. – Red cells remain viable for only about 4 months before they are removed from the blood and their components recycled in the spleen.
  41. 41. Leukocytes(wbc’s) Total• Neutrophils 60-70% (N)EVER• Lymphocytes 20-25% (L)ET• Monocytes 3-8% (M)ONKEYS• Eosinophils 1-3% (E)AT• Basophils ½ to 1% (B)ANANAS
  42. 42. eosinophilneutrophil monocyte RBC neutrophil monocyte lymphocyte lymphocyte basophil
  43. 43. Granulocytes• Granulocytes are white blood cells whose cytoplasm contains tiny granules. The cells are named according to the staining characteristics of the granules.• Neutrophils - the granules do not stain with normal blood stains so we generally see just the multilobed nucleus. – Neutrophils are phagocytic cells; they engulf foreign material• Eosinophils have red-staining granules. – They seem to be attracted to allergic reactions in the body.
  44. 44. Basophils• Basophils have dark blue-staining granules.• They are the least numerous blood cells.• They help initiate the inflammatory process at sites of injury.
  45. 45. Agranulocytes• Agranulocytes are white blood cells that have no distinct granules in their cytoplasm.• Lymphocytes have large single nuclei that occupy most of the cells. • They are an important part of the bodys immune system.
  46. 46. Lymphocytes• Monocytes are the largest of the white blood cells.• They have large pleomorphic (variously shaped) single nuclei and function mainly as phagocytic (engulfing) cells.• They are important in the long-term cleanup of debris in an area of injury.
  47. 47. Lymphocytes• Monocytes are the largest of the white blood cells.• They have large pleomorphic (variously shaped) single nuclei and function mainly as phagocytic (engulfing) cells.• They are important in the long-term cleanup of debris in an area of injury.
  48. 48. White Blood Cell Diseases• Leukopenia • Abnormally low WBC count—drug induced• Leukemias • Cancerous conditions involving WBCs • Named according to the abnormal WBC clone involved• Mononucleosis • highly contagious viral disease caused by Epstein-Barr virus; excessive # of agranulocytes; fatigue, sore throat, recover in a few weeks
  49. 49. Key ConceptsIntracellular and extracellular ion concentrations aredifferentextracellular: glucose, Na+. K+ HCO3- are a quick measureof homeostasisLipids: reveal diet and genetic make-upBUN and creatinine give you an estimate of renal functionUrine dipstick: can tell you about infection, liver and kidneyfunction, diabetes mellitus or Inspidus, metabolic state ofthe body (starvation changes)