BLOOD

1. BLOOD Chapter 14

2. Blood • Blood, a type of connective tissue, is a complex mixture of cells, chemicals and fluid. • Blood transports substances such as O2, glucose and many others throughout the body, and helps to maintain a stable internal environment. • Blood includes red blood cells, white blood cells, platelets, and plasma.

3. What’s in Blood? • A blood hematocrit is normally 45% cells and 55% plasma. • Plasma is a mixture of water, amino acids, proteins, carbohydrates, lipids, vitamins, hormones, electrolytes, and cellular wastes

4. Blood close-up Buffy coat is the layer that contains most of the white blood cells and platelets. After centrifugation, one can distinguish a layer of clear fluid (the plasma), a layer of red fluid containing most of the red blood cells, and a thin layer in between, the buffy coat (so-called because it is usually buff in hue). The buffy coat is used, for example, to extract DNA from the blood of mammals and also to detect blood parasitic diseases like malaria, since these parasites also end up in the buffy layer.

6. Where do blood cells come from? • There are two types of bone marrow: red marrow and yellow marrow. • Red blood cells, platelets and most white blood cells arise in red marrow; some white blood cells develop in yellow marrow. The color of yellow marrow is due to the much higher number of fat cells. Both types of bone marrow contain numerous blood vessels and capillaries. • At birth, all bone marrow is red. With age, more and more of it is converted to the yellow type. Adults have on average about 2.6 kg of bone marrow, with about half of it being red. Red marrow is found mainly in the flat bones such as hip bone, breast bone, skull, ribs, vertebrae and shoulder blades, and in the cancellous ("spongy") material at the proximal ends of the long bones femur and humerus. Yellow marrow is found in the hollow interior of the middle portion of long bones. • In cases of severe blood loss, the body can convert yellow marrow back to red marrow in order to increase blood cell production.

7. (Hematopoietic Stem Cell) (Red Blood Cells) (Platelets) (White Blood Cells)

8. Blood Stem Cells • Blood cells come from hematopoietic stem cells found in red marrow. • Hematopoietic cells divide • The new Progenitor cells respond to growth factors called colony-stimulating factors and turn certain genes or off • This causes differentiation of the progenitor cells and all the different blood cells are formed. • One cell type that differentiates from progenitor cells is called a Megakaryocyte, which gives rise to platelets

9. Characteristics of Red Blood Cells • Red blood cells (erythrocytes) are biconcave disks that contain one-third oxygen-carrying hemoglobin by volume. • When oxygen combines with hemoglobin bright red oxyhemoglobin results. • Deoxygenated blood (deoxyhemoglbin) is darker. • Red blood cells discard their nuclei, mitochondria* and most organelles during development and so cannot reproduce or produce proteins. *They produce ATP via glycolysis only

10. Red Blood Cell Counts • The typical red blood cell count is 4,600,000-6,200,000 cells per mm3 for males and 4,500,000-5,100,000 cells per mm3 for females. • The number of red blood cells is a measure of the blood's oxygen-carrying capacity.

11. Red Blood Cell Production and Its Control • In the embryo and fetus, red blood cell production occurs in the yolk sac, liver, and spleen; after birth, it occurs in the red bone marrow. • The average life span of a red blood cell is 120 days. • The total number of red blood cells remains relatively constant due to a negative feedback mechanism utilizing the hormone erythropoietin, which is released from the kidneys and liver in response to the detection of low oxygen levels.

12. Diet and Red Blood Cell Production • Vitamins B12 and folic acid are needed for DNA synthesis, so they are necessary for the reproduction of all body cells, especially in hematopoietic tissue. • Iron is needed for hemoglobin synthesis. • A deficiency in red blood cells or quantity of hemoglobin results in anemia.

13. Destruction of Red Blood Cells • With age, red blood cells become increasingly fragile and are damaged by passing through narrow capillaries. • Macrophages in the liver and spleen phagocytize damaged red blood cells. • Hemoglobin from the decomposed red blood cells is converted into heme and globin. • Heme is decomposed into iron that is stored or recycled and biliverdin and bilirubin are excreted in bile.

14. Sickle-cell anemia & Malaria Low oxygen levels (low blood pH) cause RBCs of people with sickle-cell anemia to sickle. Cells infected with P. falciparum parasites sickle much more readily than do uninfected cells (Roth Jr., et al., 1978). Since sickle cells are removed from the circulation and destroyed in the reticuloendothelial system, selective sickling of infected sickle trait red cells would reduce the parasite burden in people with sickle trait. These people would be more likely to survive acute malarial infections.

15. Types of White Blood Cells • White blood cells (leukocytes) help defend the body against disease. • They are formed from hemocytoblasts in response to hormones when needed. • Five types of white blood cells are in circulating blood and are distinguished by size, granular appearance of the cytoplasm, shape of the nucleus, and staining characteristics.

16. Components of WBCs The types of white blood cells are the granular neutrophils, eosinophils, and basophils, and the agranular monocytes and lymphocytes. • Neutrophils have red-staining fine cytoplasmic granules and a multilobed nucleus; they comprise 54-62% of leukocytes. • Eosinophils have coarse granules that stain deep red, a bilobed nucleus, and make up only 1-3% of circulating leukocytes. • Basophils have fewer granules that stain blue; they account for fewer than 1% of leukocytes. • Monocytes are the largest blood cells, have variably-shaped nuclei, and make up 3-9% of circulating leukocytes. • Lymphocytes are long-lived, have a large, round nucleus, and account for 25-33% of circulating leukocytes.

17. Granulocytes vs. Agranulocytes Granulocytes are a type of white Blood cell (Leukocyte) that attacks and destroys foreign substances. They have specific granules in their cytoplasm. The three different types of granulocytes have different types of specific granules. They are spherical in shape, contain nuclei. • neutrophils, • eosinophils, and • Basophils Monocytes and macrophages are agranulocytes.

18. NEUTROPHILS (Granulocytes) • The most common type of Phagocyte it makes up 50 to 70% of the White Blood Cells in the body. Neutrophils circulate freely through blood vessels, and they can squeeze between cells in the walls of a capillary to reach the site of infection.  They then engulf and destroy any pathogens they encounter. • They move form blood vessels to injured tissues due to chemotaxis – response to chemical signals sent by damaged cells Neutrophils self-destruct as they phagocytose invaders – live only for a few days

19. EOSINOPHILS (Granulocytes) • About 1.5% of leukocytes • Attack larger parasites such as blood flukes (Platyhelminthes) • Adhere to the external wall of parasite and release destructive enzymes • Do not have good phagocytic skills • May play a small role in allergic reactions • their numbers increase sharply in certain diseases, especially infections by parasitic worms.

20. Basophils (Granulocytes) • Basophils comprise less than 1% of normal blood leukocytes • Not phagocytic • Basophils leave the blood and accumulate at the site of infection or other inflammation. There they discharge the contents of their granules, releasing a variety of mediators such as histamine. • Histamine triggers blood vessel dialation – so more leukocytes can get to the site of injury • The number of basophils increases during infection.

21. MONOCYTES (Agranulocytes) • Only constitute 5% of the leukocytes, but very effective • Long-lived, excellent phagocytes for large guys • Some microbes can evade them • They circulate in the blood for some time, then they migrate into body tissues and become macrophages

22. MACROPHAGES (Agranulocytes) • Phagocytes - they consume and destroy any pathogens they encounter. They also rid the body of worn out cells and cellular debris • Some Macrophages are stationed in the tissues of the body*, awaiting pathogens, while others move through the tissues and seek out pathogens. *Some macrophages are permanent residents of specific tissues – alveolar macrophages in lungs, Kupffer’s cells in the liver, histiocytes in connective tissue, mesangial cells in the kidney and microglial cells in the brain.

23. A Macrophage is trying to engulf a fragment of stone. Even though it is too big for it and the cell lacks the enzymes to digest it, it attempts to eradicate it. The cell will probably die trying.

24. A macrophage engulfing cocci bactria

25. Natural Killer Cell (Lymphocyte) • Do not kill the pathogen directly • Their specific function is to destroy virus-infected body cells and cancerous cells • They attack the infected cell’s membrane and cause it to lyse

26. HIV infected LymphocyteThe blue particles is the virus progeny exiting the cell

27. Summary of Functions of WBCs • Leukocytes can squeeze between cells lining walls of blood vessels by diapedesis and attack bacteria and debris. • Neutrophils and monocytes are phagocytic, with monocytes engulfing the larger particles. • Eosinophils moderate allergic reactions as well as defend against parasitic infections. • Basophils migrate to damaged tissues and release histamine to promote inflammation and heparin to inhibit blood clotting. • Lymphocytes are the major players in specific immune reactions and some produce antibodies.

28. WBCs

29. White Blood Cell Counts • Normally a cubic milliliter of blood contains 5,000 to 10,000 white blood cells. • Leukocytosis is an elevation of the white blood cell count. It is very common in sick people. It occurs in response to viral, bacterial, fungal, or parasitic infections, cancer (leukemia), and exposure to certain medications or chemicals. • Leukopenia is a decrease in the number of circulating white blood cells (leukocytes) in the blood. As the principal function of white cells is to combat infection, a decrease in the number of these cells can place patients at increased risk for infection. • A differential white blood cell count can help pinpoint the nature of an illness, indicating whether it is caused by bacteria or viruses. • A differential white blood cell count lists the percentages of the types of leukocytes in a blood sample.

30. Blood Platelets • Blood platelets are fragments of megakaryocytes, produced in red marrow • Thrombopoietin is a hormone, mainly produced by the liver, that stimulates platelet production. • Platelets help repair damaged blood vessels by adhering to their broken edges. • Normal counts vary from 130,000 to 360,000 platelets per mm3. • Thrombopenia, or low platelet counts increase bleeding risks • Thrombocytosis or high platelet count may lead to thrombosis (clotting, bruising, strokes, heart attacks).

31. Blood Plasma • Plasma is the clear, straw-colored fluid portion of the blood. • Plasma is mostly water but contains a variety of substances. • Plasma functions to transport nutrients and gases, regulate fluid and electrolyte balance, and maintain a favorable pH.

32. Plasma Proteins • The plasma proteins are the most abundantly dissolved substances in the plasma. • Plasma proteins are not used for energy and fall into three groups--albumins, globulins, and fibrinogen. • The albumins help maintain the osmotic pressure of the blood and account for 60% of the plasma proteins. • The globulins, comprising 36% of the plasma proteins, are designated as alpha, beta, and gamma globulins. • Alpha and beta globulins function in transporting lipids and fat-soluble vitamins. • Gamma globulins are a type of antibody. • Fibrinogen (4%) plays a primary role in blood coagulation.

33. Nutrients and Gases • The most important blood gases are oxygen and carbon dioxide. • The plasma nutrients include amino acids, monosaccharides, nucleotides, and lipids. • Since lipids are not soluble in the water of the plasma, they are surrounded by protein molecules for transport through the bloodstream as lipoproteins. • Lipoproteins are classified on the basis of their densities, which reflects their composition. • Types of lipoproteins include HDL, LDL, VLDL, and chylomicrons.

34. Nonprotein Nitrogenous Substances • Nonprotein nitrogenous substances generally include amino acids, urea, and uric acid. • Urea and uric acid are the by-products of protein and nucleic acid catabolism.

35. Plasma Electrolytes • Plasma electrolytes are absorbed by the intestine or are by-products of cellular metabolism. • They include sodium, potassium, calcium, magnesium, chloride, bicarbonate, phosphate, and sulfate ions. • Some of these ions are important in maintaining osmotic pressure and pH of the plasma.

36. Hemostasis • Hemostasis refers to the stoppage of bleeding. • Following injury to a vessel, three steps occur in hemostasis: • blood vessel spasm, • platelet plug formation, and • blood coagulation.

38. Blood Vessel Spasm • Cutting a blood vessel causes the muscle in its walls to contract in a reflex, or engage in vasospasm. • This reflex lasts only a few minutes, but it lasts long enough to initiate the second and third steps of hemostasis.

39. Platelet Plug Formation • Platelets stick to the exposed edges of damaged blood vessels, forming a net with spiny processes protruding from their membranes. • A platelet plug is most effective on a small vessel.

40. Blood Coagulation Blood coagulation is the most effective means of hemostasis. Blood coagulation is very complex and uses clotting factors. • Damaged tissues release a chemical called tissue thromboplastin, which activates the first in a series of factors leading to the production of prothrombin activator. • Prothrombin activator converts prothrombin in the plasma into thrombin. This in turn, catalyzes a reaction that converts fibrinogen into fibrin. • The major event in blood clot formation is the conversion of soluble fibrinogen into net like insoluble fibrin causing the blood cells to catch. • The amount of prothrombin activator formed is proportional to the amount of tissue damage. • Once a blood clot forms, it promotes still more clotting through a positive feedback system. • After a clot forms, fibroblasts invade the area and produce fibers throughout the clots. A clot that forms abnormally in a vessel is a thrombus; if it dislodges, it is an embolus.

41. Clotting in a Nutshell Damaged tissue  Thromboplastin  Prothrombin activator  Thrombin  Fibrinogen (soluble) into Fibrin (insoluble)  Net-like Clot

42. Blood Groups and Transfusions Antigens and Antibodies • Clumping of red blood cells following transfusion is called agglutination. • Agglutination is due to the interaction of proteins on the surfaces of red blood cells (antigens) with certain antibodies carried in the plasma. • Only a few of the antigens on red blood cells produce transfusion reactions. • These include the ABO group and Rh group.

43. ABO Blood Group • Type A blood has A antigens on red blood cells and anti-B antibodies in the plasma. • Type B blood has B antigens on red blood cells and anti-A antibodies in the plasma. • Type AB blood has both A and B antigens, but no antibodies in the plasma. • Type O blood has neither antigen, but both types of antibodies in the plasma. • Adverse transfusion reactions are avoided by preventing the mixing of blood that contains matching antigens and antibodies. • Adverse reactions are due to the agglutination of red blood cells.

44. Rh Blood Group • The Rh factor was named after the rhesus monkey. • If the Rh factor surface protein is present on red blood cells, the blood is Rh positive; otherwise it is Rh negative. • There are no corresponding antibodies in the plasma unless a person with Rh-negative blood is transfused with Rh-positive blood; the person will then develop antibodies for the Rh factor. • Erythroblastosis fetalis develops in Rh-positive fetuses of Rh-negative mothers but can now be prevented

45. THE END