Heme: 1:00-2:00Scribe: Andrew Treece

Tuesday, Oct 20, 2009Proof: Patricia Fulmer

Dr. CotlinBlood Composition and FunctionPage1 of 4

The audio from this lecture was spotty and hard to hear, but Dr. Cotlin pretty much read off of her slides.

  1. Blood: Cellular Composition and Function [S1]
  2. General Features of Blood [S2]
  3. Basically, blood is a connective tissue that consists of cells and extracellular matrix.
  4. Adults usually have 5-6 liters of blood.
  5. There are RBCs and platelets (cell fragments). There are also WBCs and of those only the lymphocytes can reenter the vasculature.
  6. Functions of Blood [S3]
  7. The basic most fundamental function it to carry oxygen. They are full of hemoglobin to carry oxygen.
  8. It also has a buffering system with albumin that helps maintain the balance in blood. The blood is slightly alkaline at a pH of about 7.4.
  9. Blood has temperature control in conjunction with constriction or dilation of vessels.
  10. There is removal of waste and small molecules through the blood and kidney system.
  11. The blood is used for immune function in that the WBCs play a role in the immune response.
  12. All of the clotting factors are in the blood in inactive form but there is a cascade that activates this chain of reactions to cause clotting.
  13. The hematocrit of human blood [S4]
  14. Hematocrit is the volume of packed erythrocytes (the volume of cells in the blood).
  15. About 45% of blood volume is going to be cells.
  16. Hematocrit is a percentage of blood that is cellular material. It is usually a little higher in males in part to menstruation.
  17. Leukocytes relative to RBCs only make up about 1% of the blood volume.
  18. Major Fluid Components of Blood [S5]
  19. The fluid total is called plasma and constitutes about 55% of the total volume of blood.
  20. If you want to monitor blood without its coagulating factors you will measure it in the form of serum which is blood plasma without the clotting factors.
  21. Blood also has albumin, immunoglobulins, complement, lipoproteins, other transporters, fibrinogen (for clotting), hormones, electrolytes, and more.
  22. Cells of the Blood [S6]
  23. Cells make up roughly 45% of the blood volume.
  24. 99% of this is going to be RBCs. WBCs basically make up the other 1%.
  25. WBCs are categorized into two main groups: granulocytes and agranulocytes
  26. Granulocytes have prominent cytoplasmic granules in their cytoplasm, and they are packed with specific proteins and molecules. They will run around the body and wait for a signal and in response they will release the granules. Basically this is for the innate immune response.
  27. Granulocytes include neutrophils (PMNs, polymorphonuclear leukocytes), eosinophils, and basophils.
  28. Agranulocytes include monocytes and lymphocytes.
  29. Histology slide [S7]
  30. This is just a basic blood smear and you can see all of the RBCs and three prominent WBCs.
  31. The little dark pieces of stained material are the platelets.
  32. The standard stain is called Wright’s stain, and the granules stain differently in eosinophils, basophils, and neutrophils.
  33. Cells and platelets of circulating blood [S8]
  34. Basophils will stain very dark purple. Eosinophils will stain reddish. Neutrophils will stain neutrally.
  35. Lymphocytes and monocytes don’t stain this way because they don’t have the granules.
  36. Histology slide [S9]
  37. This is just another picture of the blood cells.
  38. You can see a lymphocyte, monocyte, PMN, neutrophils, eosinophils, and basophil.
  39. The Granulocyte Series of WBCs [S10]
  40. skipped
  41. Neutrophils or PMNs [S11]
  42. The most abundant by far of all leukocytes are the neutrophils (PMNs).
  43. You usually see three to five lobes and sometimes when it is cut in section it looks like it has two small nuclei but it is really one.
  44. Properties / Functions of PMNs [S12]
  45. These are the main phagocytes of the blood and these will be the first line of defense especially against small bacteria.
  46. They are produced in abundance of about 80g per day. They circulate for about 10 hours then leave the vasculature and just migrate in the body like in the GI tract and other places. They just hang around waiting to clear out debris.
  47. They have large stores of glycogen.
  48. They have two primary granules: elastase and myeloperoxidase. They also have lysozyme and proteases. Most of their granules contain enzymes that are going to digest things like proteins and lipids and more.
  49. Diagram [S13]
  50. They have receptors on their surface. This will happen when a bacteria comes into play.
  51. It is going to be bound by either antibodies or complement where there is a prominent receptor on the nucleus.
  52. It will be taken in by phagocytosis and it will release its granules into that phagosome. It isn’t really releasing its granules to the outside, but more inside for intracellular digestion.
  53. It is internal digestion.
  54. Neutrophils [S14]

a. Again you can see that PMNs are a little larger than RBCs.

  1. Eosinophil [S15]

a. The next type is the eosinophils. The granules look kind of reddish orange on normal histology slides.

b. It kind of has a lobed nucleus that is pretty large. These are larger than RBCs.

  1. Eosiniphils [S16]
  2. These are going to leave circulation after about one day, and they will also be involved in infections.
  3. These are really critical in parasitic infections.
  4. Eosinophils secrete their secretory granules and one of the major secretions is called major basic protein (MBP) which binds and disrupts the membranes of parasites.
  5. They also release histamine which triggers the signal for WBCs to be sent to the area.
  6. Eosinophils are also going to release these histamine loaded granules in response to allergens.
  7. They all have surface receptors for IgE which is the antibody seen mostly in allergic responses.
  8. Eosinophil histology [S17]
  9. You can see in this slide the reddish color.
  10. They are bi-lobed.
  11. Basophil [S18]
  12. The one on the right is a basophil and on the left is a neutrophil.
  13. Many times the granules of basophils stain so dense that you can’t see the nucleus.
  14. Basophils [S19]
  15. These have the lowest number in circulation (less than 1% of all WBCs).
  16. Their granules have a prominent component of heparin. This is going to set off a series of reactions for increasing these vasoactive components that regulate blood flow. These will play a role in things like asthma.
  17. Basophil and Lymphocyte histology [S20]
  18. Here is a lymphocyte and a basophil.
  19. Again, you can’t really see the nucleus of the basophil because it is drowned out but the staining of the granules.
  20. The Agranulocyte series of WBCs [S21]
  21. There are two types: lymphocytes and monocytes.
  22. Lymphocytes [S22]
  23. Lymphocytes can be termed small or large and are about the size of an RBC maybe a little larger.
  24. The larger lymphocytes will be considerably larger than RBCs.
  25. One of the main characteristics of lymphocytes is the very distinct round nucleus.
  26. Usually you can only see a thin sliver of cytoplasm.
  27. Lymphocytes [S23]
  28. Next to neutrophils, these are the most abundant at about 30-40% of the total WBCs.
  29. ***NOTE: the measurements for the two sizes should be micrometers and not millimeters
  30. A RBC is about 8 microns and the large lymphocyte is about 9-12 and the small about 6-8 microns.
  31. The cytoplasm stains lightly and appears as a small rim around the nucleus.
  32. We can have B-lymphocytes (Bcells), T-lymphocytes(Tcells), and natural killer cells (NK cells).
  33. These will all play a role in adaptive immunity and secreting antibodies to antigens we have seen before.
  34. You cannot distinguish B and T cells Histologically without special staining techniques.
  35. These leave the vasculature like everything else, BUT these are the only ones that CAN re-enter the vasculature. So this makes sense with adaptive immunity and responding to things we’ve seen before.
  36. Most lymphocytes circulating in the blood are immunocompetent meaning they have the capacity to recognize and respond to antigens. These are the ones that are going to go back into the blood stream and wait in the body until you are exposed to that antigen for a second time.
  37. Some of the B cells can mature into Ig producing plasma cells.
  38. Lymphocyte Histology [S24]
  39. Monocyte [S25]
  40. Monocyte [S26]
  41. Monocytes are also phagocytic cells and are pretty large. They usually have a kidney shaped nucleus or horseshoe shaped nucleus. They are a large bulky cell with a large nucleus.
  42. These will circulate in the blood for a few days then migrate into the tissue.
  43. These will be found hanging around in the epithelium, the respiratory tract, GI tract, and other places.
  44. Once they leave the circulation they differentiate into macrophages. The difference between a monocyte and macrophage are their location: monocytes are in the blood and macrophages are in the tissues.
  45. These phagocytose bacteria as well as large molecules like other cells and cell debris. They express MHC class II molecules. MHC II means that this cell has taken something up, chopped it up, and presented it.
  46. So, neutrophils phagocytize small bacteria and digest them intracellularly. Macrophages can engulf very large things in addition to small things.
  47. Macrophages [S27]
  48. In the tissue macrophages are sometimes called professional phagocytes.
  49. They are named differently in different parts of the body: liver (kupfer cells), bone marrow (osteoclasts), skin (histiocytes), lungs (alveolar macrophages, or dust cells), nervous system (microglial cells)
  50. So these are really just cells that come from monocytes that leave and get into the tissue. We also have macrophages in the GI tract and repro tract and almost any other place in the body that might be exposed.
  51. Monocyte [S28]

a. This is what they look like in the blood, large and kidney shaped.

  1. The Erythrocyte [S29]
  2. The erythrocyte looks like a biconcave disk and is extremely pliable and have to squeeze through the capillaries which are usually just a little wider than an RBC.
  3. The major protein is hemoglobin. The other molecules are basically for housekeeping and are mainly glycogen granules.
  4. They have no nucleus or organelles.
  5. They last about 120 days, and shortly after they are formed they expel their nucleus. They load their cytoplasm with as much hemoglobin as they can make.
  6. Their main fundamental role is to just carry oxygen.
  7. They are phagocytosed by macrophages in the spleen, liver, and bone marrow
  8. Oxygen Content of Blood in Vasculature [S30]
  9. If we look at the oxygen pressure, the gas exchange takes place at the level of the capillaries.
  10. In the lung where hemoglobin is reoxygenated is where there is the highest oxygen pressure.
  11. Normal and Sickle RBCs [S31]
  12. The normal RBC looks like a doughnut.
  13. A sickle cell forms mutated polymers. A normal cell has two alpha and two beta subunits for hemoglobin, and in a sickle cell a beta subunit is mutated.
  14. All those mutated beta chains stick together and form long polymers and because the membrane is so pliable the long polymers cause the whole cell to change shape. This makes the cell unable to be reoxygenated.
  15. This happens a lot in the joints where there is accumulation of these sickle cells. These clog up the vasculature and everything downstream is put in jeopardy.
  16. Features of Erythrocyte membrane [S32]
  17. The membrane is very pliable. Don’t remember all of these molecules.
  18. There is a network of anchoring molecules. The major components are these spectrin molecules. Spectrin is a heterodimer that is very elastic and pliable and gives that property to the RBC.
  19. The inside of the cytoplasm is just a network of these molecules.
  20. Platelets [S33]
  21. Platelets (aka Thrombocytes) [S34]
  22. Platelets are not really cells, but are just cell fragments.
  23. The megakaryocytes are cells in the bone marrow that give rise to the platelets. They are large cells and pieces of these cells pinch off. There are a few granules in these.
  24. Almost everything platelets are involved with is to mediate clotting. The lifespan of these is about ten days.
  25. They have receptors that bind to type IV collagen which is mostly in basement membranes.
  26. What happens is that a clotting reaction is triggered by a breach in the endothelium. All blood vessels are lined by endothelium, so when it is damaged you are exposing the tissue of the basement membrane underneath and triggering the platelet to bind there. This leads to the whole clotting response.
  27. The platelets bind and form a plug, and they release their granules that lead to a clotting cascade and the formation of fibrin which is a polymer that crosslinks the platelets. Secondary reactions are going to recruit other molecules to replace the damage as well.
  28. Additional platelet functions [S35]
  29. They have granules: alpha-dense granules and dens core granules
  30. One of the major components is the platelet derived growth factor (PDGF) from alpha dense granules. This helps basically to induce the cells around it to activate and undergo mitosis.
  31. Another set of granules facilitates adhesion and vasoconstriction. Vasoconstriction is important to stop bleeding and prevent blood loss.
  32. Structure of platelets [S36]
  33. Platelets are just pieces of molecules so basically they have a different composition. Whatever was pinched off is what you will see in the platelet.
  34. The origin of platelets [S37]
  35. Here is a picture of megakaryocytes.
  36. Imagine a blood vessel. All of this is in a sinusoid in the bone trabeculum where all of the marrow is.
  37. This is where all of those cells are maturing.
  38. Platelets are just those little pieces of magakaryocytes.
  39. Histology [S38]
  40. This is bone marrow cells and you can see large cells. Megakaryocytes give rise to platelets.
  41. Formation of blood cells (hemopoiesis) [S39]
  42. In fetal and early life hemopoiesis (formation of blood cells) takes place in the spleen. Only shortly after birth does that function transport to the bone marrow.
  43. All blood cells are formed from a common stem cell and development is controlled by cytokines and other mediators.
  44. 1011 blood cells enter the circulation on a given day.
  45. Erythropoietin (EPO) controls RBC production. A version of this is used as a drug to help people with decreased RBC count.
  46. Hematopoietic stem cells [S40]
  47. A pluripotent stem cell is just one that can give rise to all types of blood cells.
  48. Then there are just different levels of differentiation.
  49. A multipotential stem cell is specific but has a wide range of cell types.
  50. A committed progenitor cell is capable of one or two cell types.
  51. Precursors or blasts are going to be going through the differentiation process.
  52. Precursors or blasts and mature cells are committed.
  53. Chart [S41]

a. A pluripotent cell can still be anything, and there are two lineages.

b. The lymphoid lineage basically gives rise to lymphocytes.

c. The myeloid lineage gives rise to everything else. All of the macrophages, monocytes, etc.

  1. The blood clotting process [S42]
  2. We can have a breach that occurs outside of the vasculature or inside of the vasculature.
  3. The extrinsic pathway and intrinsic pathway emerge in a common pathway.
  4. There is a molecule called Factor X which cleaves prothrombin to thrombin. Thrombin is an enzyme that cleaves fibrinogen to fibrin. Fibrin is the little molecule that binds to platelets to form a blood clot.
  5. A blood clot is really fibrin monomers crosslinked with platelets to make a meshwork.
  6. Diseases of RBCs : Anemia [S43]
  7. The most common cause of anemia is iron deficiency.
  8. Blood cells table [S44]
  9. Summary chart to look at on your own.

(end time 43:42)