Lecture 2 blood
- 2. BLOOD CELL FORMATION (HEMATOPOIESES or HEMOPOIESIS) The primary site of blood cell formation after birth and into adulthood is the RED BONE MARROW (MYELOID TISSUE). The red bone marrow is chiefly found in the SPONGY BONE of the PROXIMAL EPIPHYSES of the HUMERUS & FEMUR; FLAT BONES such as the STERNUM, RIBS & CRANIAL BONES; and the VERTEBRAE & PELVIS. All of the formed elements arise from the same type of cell, the PLURIPOTENT HEMATOPOIETIC STEM CELL, which resides in the RED BONE MARROW. Each formed element has a different maturation pathway. Hormones control differentiation and maturation of the formed elements. After the cells mature, they are discharged into the bloodstream.
- 4. Blood Function • It carries oxygen and nutrients to the cells throughout the body • It carries CO2 and wastes away from the cell • It contains cells and agents that defend the body against infection • It contains hormones and enzymes that regulate body activities • It regulates body Temperature
- 5. Circulating Blood Cells The total volume of blood of an average adult is about 5 L, and it circulates throughout the body within the confines of the circulatory system. Blood is a specialized connective tissue composed of formed elements and a fluid component (the extracellular matrix) known as plasma (55%). The formed elements (45%) are composed of blood cells and cell fragments, known as platelets. Light microscopic examination of the formed elements is performed using either the Wright or Giemsa stains, and identification of blood cells is based on the colors produced by these stains.
- 6. I. Fluid component – plasma (water and solute). B. Plasma proteins - 7% by volume a. albumin b. fibrinogen c. alpha, beta, and gamma globulins - gamma globulins are IgG antibodies (immunoglobulins) A. Water - 90% C. Inorganic salts - 0.9% by volume Blood electrolytes such as Sodium, Potassium, and calcium salts. D. Other organic molecules - 2.1% by volume vitamins, amino acids, regulatory peptide <hormones>, steroid hormones , and lipids)
- 7. Circulating Blood Cells The cells of blood are subdivided into two major components, red blood cells (RBC) and white blood cells (WBCs, leukocytes). Red blood cells lose their nuclei and organelles during development, therefore mature, circulating RBC are anucleated cells whose cytoplasm is filled with hemoglobin. White blood cells are subdivided into two categories, those without specific granules, agranulocytes and those housing specific granules, granulocytes. Lymphocytes and monocytes belong to the former and neutrophils, eosinophils, and basophils belong to the latter category. Platelets are round to oval cell fragments, lack nuclei and originate by budding from large cell in the bone marrow called megakaryocytes.
- 8. ERYTHROCYTES (RED BLOOD CELLS or RBC's) Women usually have about 4.8 million RBC's per microliter of blood, while males have about 5.4 million RBC's per microliter of blood. There are 1,000 microliters in a milliliter and about 50 microliters in one drop of blood. 2million produced/second. The major function of erythrocytes (RBC's) is to pick up OXYGEN in the lungs and distribute it to the body cells. RBC's have many adaptations that allow them to perform this function efficiently. The erythrocyte diameter is about 8 micrometers. The erythrocyte has a BICONCAVE DISC shape. See FIG. The small size and biconcave disc shape provide a large surface area (the plasma membrane) to internal volume (cytosol) ratio. The biconcave disc-shaped red blood cell is ideally suited for gas exchange (picking up oxygen) because of greater surface area for diffusion of gas molecule into and out of the RBC than would be sphere or a cube.
- 9. The erythrocyte's shape is not rigid. The RBC is very flexible. RBC's can twist, turn and become cup-shaped as they travel through tiny, microscopic blood vessels. RBC's have NO NUCLEUS. They also have NO MITOCHONDRIA, which use oxygen to make ATP. Erythrocytes are able to make ATP anaerobically (without oxygen). The function of oxygen transport in RBC's is performed by the red protein pigment, HEMOGLOBIN, which is found in the cytosol of RBC's and makes up about 33% of the erythrocyte weight.
- 10. Each hemoglobin molecule contains 4 "heme" groups, and each heme group contains an iron atom (Fe2+) carry one oxygen). The IRON binds reversibly with oxygen, so that each hemoglobin molecule can carry up to 4 molecules of oxygen. It has been estimated that each RBC contains about 280 million hemoglobin molecules, so each RBC can carry over 1 billion molecules of oxygen. When oxygen binds to hemoglobin, it becomes bright scarlet red. When hemoglobin releases oxygen, it becomes a dark, purplish red.
- 11. Notice that hemoglobin binds reversibly with oxygen , forming oxyhemoglobin and to carbon dioxide, forming carbaminohemoglobin. Carbon monoxide, on the other hand, binds irreversibly with hemoglobin, which is why it is so dangerous. Carbon monoxide can prevent hemoglobin from binding to oxygen. RBC's live for only about 120 days before they are worn out by the wear and tear their plasma membranes undergo as they squeeze through microscopic blood vessels. RBC's are removed from circulation and destroyed by macrophages in the LIVER and SPLEEN. RBC's placed in hypotonic: Swell and burst a process called hemolysis RBC's placed in hypertonic: Shrink a process called plasmolysis.
- 12. The plasma membrane’s surface of the red blood cell has specific inherited carbohydrate chains that act as antigens (agglutinogins) and determine the blood group of an individual for the purposes of blood transfusion. The most notable of these are the A and B antigens, which determine the four primary blood groups, A, B, AB, and O Another important blood group, the Rh group, is so named because it was first identified in rhesus monkeys. Three of the Rh antigens (C, D, and E) are so common in the human population that the erythrocytes of 85% of people have one of these antigens on their surface, and these individuals are thus said to be Rh+. The blood of the remaining 15% lacked the factor and was typed Rh negative
- 14. LEUKOCYTES LEUKOCYTES (WHITE BLOOD CELLS or WBC's) are far less numerous than RBC's, but they are crucial to the body's defense against disease. Leukocytes account for less than 1% of total blood volume. On average there are 6000-9000 WBC's per microliter of blood. Leukocytosis: increase above 10000 per microliter of blood. (stress, microbes, surgery, anesthesia) Leukopenia: abnormally low level less than 5000 per microliter of blood (radiation, shock, chemotherapy) WBC's are nucleated and the contain the usual cell organelles, but do not contain hemoglobin. WBC's are larger than red blood cells. Most leukocytes are able to slip into and out of blood vessels and they use the circulatory system as a transportation system to carry them to areas of the body where they are needed. These leukocytes move through the tissue spaces by diapedesis ("amoeboid" movement).
- 15. There are 2 main groups of leukocytes: GRANULAR and AGRANULAR LEUKOCYTES. GRANULAR LEUKOCYTES are also called POLYMORPHONUCLEAR GRANULOCYTES (PMN's). PMN's have multi-lobed nuclei and contain prominent granules in the cytosol. Some PMN's contribute to the inflammatory response, which is the body's response to an infection. Symptoms of the inflammatory response include the following: 1. CAPILLARIES DILATE and become PERMEABLE ("leaky") so that it is easier for WBC's to enter infected tissues. 2. Increase in capillary permeability ("leakiness") causes tissue EDEMA (swelling due to fluid accumulation). 3. The infected area becomes WARM to the touch. This warmth increases the metabolic activity of WBC's that are fighting the infection. 4. Inflammation walls off the infection so that it does not spread into the bloodstream.
- 16. There are 3 kinds of PMN's based on their staining properties in standard blood smears: NEUTROPHILS, EOSINOPHILS and BASOPHILS. The cytosol of NEUTROPHILS stains pink and the cytosol granules stain pale lilac. They are 10-12 micrometers in diameter. The nucleus consists of 2-5 lobes. Neutrophils make up 60-70% of all WBC's in blood and are also scattered in many tissues. They contain small numerous granules that Can be considered as lysosomes. These lysosomes hydrolyze bacteria, debris, and fungi. Neutrophils are attracted to chemicals released by bacteria and necrotic (dying) tissue during infection (they exhibit "positive chemotaxis") and are the first to arrive during an inflammatory response. Neutrophils are "kamikaze" phagocytes. After ingesting the microbe, the neutrophil metabolically "cremates“ the ingested microbe. About 1.6 billion neutrophils are turned over daily. Unfortunately, this results in the death of the neutrophil as well. Because of this, neutrophils have a lifespan that ranges from a few hours (during an acute infection) to a few days. (12-16hr in blood stream, 1-4 days in tissue)
- 17. BASOPHILS have prominent blue-staining cytosol granules that nearly obscure the nucleus. Basophils have an irregular, clover leave shaped nucleus. . Basophils are 8-10 micrometers in diameter and make up 0.5-1.0 % of total circulating WBC's. Some basophils settle into tissues and become MAST CELLS. Basophils and mast cells release pharmacologically active ingredients, such as heparin and histamine. Heparin is an anticoagulant (it prevents blood clotting). Histamine stimulates vasodilation of capillaries and capillary permeability (in other words, it makes the blood vessels "leaky"), which causes tissue edema (swelling). Histamine also contributes to smooth muscle contraction of bronchioles (as in asthma). All of these chemicals contribute to the inflammatory response and the chemicals also attract neutrophils to the site of infection ("positive chemotaxis"). Extracellular basophils are seen often at the sites of inflammation and major cell types of cutaneous basophil hypersensitivity.
- 18. EOSINOPHILS have prominent red-stained cytosol granules and a bilobed nucleus. The cytosol granules contain hydrolytic enzymes (e.g peroxidoase). These granules can be cionsidered as lysosomes. Eosinophils are 11-14 micrometers in diameter and make up 2-4% of the total white blood cell population. (4 and 5 days life span, 8-12 days in tissue. Eosinophils are also found in elevated numbers during allergic reactions and in response to parasitic infection, and they may function in producing chemicals that limit inflammation.
- 19. AGRANULAR LEUKOCYTES do not contain prominent granules in the cytosol. There are 2 main types of agranular leukocytes: MONOCYTES and LYMPHOCYTES. 1. MONOCYTES are large cells (10-20 micrometers in diameter) with a kidney- bean shaped nucleus. Monocytes make up 3-8 % of total WBC population. Monocytes are found in the bloodstream, but move into tissues to become MACROPHAGES. When monocytes move into infected tissues they become WANDERING MACROPHAGES, engulfing cell debris and bacteria. Macrophages follow neutrophils into infected areas. Most tissues in the body contain resident populations of macrophages that protect the tissue from infection. These macrophages are called FIXED MACROPHAGES.
- 20. Fixed macrophages have different names depending upon their location: a. epidermis of skin: LANGERHANS CELL b. bone: OSTEOCLAST c. connective tissue: HISTIOCYTE d. lung: ALVEOLAR MACROPHAGE e. nervous tissue:: MICROGLIAL CELL f. liver: KUPFFER'S CELL The fixed macrophages of the LIVER and SPLEEN engulf and destroy old, worn-out RBC's, WBC's and platelets.
- 21. 2. LYMPHOCYTES have a large nucleus surrounded by a small amount of cytosol, and are about 10 micrometers in diameter. They constitute 30-35% of total circulating WBC's. There are 2 main types of lymphocytes: B CELLS and T CELLS. B CELLS When B CELLS (B LYMPHOCYTES) encounter foreign antigen (cell markers on bacteria and viruses), they proliferate (reproduce) and differentiate (specialize) by mitosis into PLASMA CELLS and MEMORY CELLS. PLASMA CELLS produce antibodies or immunoglobulins that destroy bacteria and render their toxins harmless. MEMORY CELLS are long-lived , they return to an inactive state and can respond to the same infection years later (with the same antigen).
- 22. T lymphocytes Make 80% of lymphocytes in blood and serve as the major cells of the cell- mediated immunity. They produce a variety of factors, called lymphokines that influence the activities of macrophages and of other leukocytes involved in an immune response. They have life span measured in years in human There are 2 kinds of T cells: KILLER T CELLS and HELPER T CELLS. KILLER (CYTOTOXIC) T CELLS destroy cancerous tumor cells and virally infected cells. HELPER T CELLS are said to "orchestrate the immune response" by producing chemicals called cytokines. Cytokines are chemical messengers that control the immune responses of T cells and B cells. Human immunodeficiency virus (HIV), which causes AIDS, infects and kills helper T cells.
- 23. Whenever WBC's are mobilized due to infection, the body speeds up the production of WBC's and twice the normal number may appear in the blood within a few hours. A WBC count over 10,000 cells per cubic millimeter indicates that a bacterial, viral or parasitic infection is taking place. An increase in WBC counts can also occur during severe allergies, burn injuries, cancers, and autoimmune diseases. Physicians use white blood cell counts to help diagnose infections, disorders, cancers, and allergic reactions.
- 24. Platelets or Thrombocytes Platelets are enucleate disk-like cell fragments that are 2-5 μm diameter often appear in clumps in blood smears. Function in clotting. PLATELETS are fragments of large cells called MEGAKARYOCYTES developed from bone marrow stem cell. When the megakaryocyte matures, it ruptures and releases cell fragments (2000-3000) into the blood stream. There are between 250,000 and 400,000 platelets per mm3 of blood, each with a life span of less than 14 days.. Platelets are essential for the clotting process that occurs in plasma when blood vessels are ruptured. By clumping together at the damaged site, platelets form a temporary plug that helps seal the break. Figure Platelet ultrastructure. Note that the periphery of the platelet is occupied by actin filaments that encircle the platelet and maintain the discoid morphology of this structure.
- 25. Clot formation: The platelet plasma membrane has numerous receptor molecules as well as a relatively thick glycocalyx. (clotting factor I-XIII) If the endothelial lining of a blood vessel is disrupted and platelets come in contact with the endothelial lining of the damaged vessele slowing or stopping bleeding, they become activated, release enzyme thromboplastin which transfer prothrombin into the enzyme thrombin. Thrombin , in turn, activates fibrinogen into fibrin, a thread like protein. Serotonin, a vsoconstrictor substance secreated by platelets, restricts blood flow at the site of injury. Interactions of tissue factors, plasma-borne factors, and platelet-derived factors form a blood clot. Platelets age quickly in the bloodstream and degenerate in 5-9 days if they are not involved in clotting. Old platelets are removed from circulation and destroyed by fixed macrophages in the spleen and liver.