Blood Composition and Function General Composition of Blood Plasma Formed Elements Erythrocytes Leukocytes Hematopoesis In a unicellular organism, functions like nutrient, gas, and waste transport can be easily performed by simply dumping the waste into the external environment. In a multicellular organism, it is not possible for a single cell to access respiratory gases, nutrients, and to get rid of waste since it is buried in a community. Therefore, groups of cells have to specialize into tissues to take on these services. Nowhere in the body is this more obvious than with the blood and the blood transport system. Blood is the river of life that delivers nutrients and oxygen and takes away wastes from every cell. It is also important in distributing and maintaining body heat. Blood is the only fluid tissue. The composition and functioning of the blood reveals how this river can perform this essential function.

Blood Composition The only fluid tissue in the human body Classified as a connective tissue Living cells = formed elements Non-living matrix = plasma Color range Oxygen-rich blood is scarlet red Oxygen-poor blood is dull red pH must remain between 7.35–7.45 Blood temperature is slightly higher than body temperature Blood is a complex connective tissue composed of formed elements like blood cells and a nonliving fluid matrix called the plasma. Blood is analyzed in a laboratory by spinning a sample in a centrifuge so the heavier elements settle out. The reddish mass at the bottom of the tube consists of erythrocytes that are responsible for oxygen and carbon dioxide transport in the blood. Erythrocytes make up about 45 % of the total blood volume. When a blood sample is centrifuged in a thin capillary tube in order to measure the percentage of red blood cells (to check, say, for anemia), this value is known as the hematocrit. Floating on top of the reddish mass is a thin, whitish layer called the buffy coat. The buffy coat contains leukocytes involved in body defense and platelets (fragments of cells) involved in blood clotting. It makes up less than 1 percent of the volume. Finally, the translucent, yellowish plasma makes up the remaining 55 percent of the volume. Plasma The plasma is about 90 percent water and contains over 100 different substances like nutrients, salts, gases, hormones, plasma proteins, and wastes. Plasma proteins are the most abundant solutes. They include albumin, fibrinogen, prothrombin, and globulins (immunoglobulins), and protein-based hormones. Aside from globulins and hormones, most plasma proteins are produced by liver cells. Plasma proteins remain in the blood and are not taken up by cells, unlike the other components of blood. Albumin contributes to the osmotic pressure of blood to keep water in the bloodstream. Fibrinogen and prothrombin are clotting proteins that are involved in hemostasis or damming leaking blood. Immunoglobulins (antibodies) are attack molecules that clear the body of pathogens. Plasma composition varies continuously as cells add or remove substances to the blood. Various homeostatic mechanisms of the body keep concentrations relatively constant. The liver maintains a fairly constant plasma protein level by increasing production if concentrations are too low. The hypothalamus monitors blood pH and stimulates the respiratory system and kidneys to act in the case of acidosis or alkalosis to keep the pH at 7.35-7.45. Various other body organs make a multitude of adjustments to the plasma solutes. Figure 10.1

Blood Cell Types Figure 10.2 Formed Elements The formed elements of blood are the living cells found within it. These are erythrocytes, leukocytes, and platelets. Wright's stain is a popular dye used to highlight red blood cells and especially the nuclei of white blood cells. Figure 10.2

Erythrocytes (Red Blood Cells) The main function is to carry oxygen Anatomy of circulating erythrocytes Biconcave disks Essentially bags of hemoglobin Anucleate (no nucleus) Contain very few organelles Outnumber white blood cells 1000:1 Erythrocytes Red blood cells (RBCs) are surprisingly very little like the average eukaryotic cell although they originate as standard cells with all the usual organelles. During their maturation in the bone marrow, red blood cells produce large amounts of the iron-containing protein hemoglobin (Hb) that binds both oxygen and carbon dioxide inside the erythrocyte. Subsequently red blood cells lose their nucleus (becoming anucleate), mitochondria, and other organelles, becoming literally bags of hemoglobin. RBCs are relatively tiny eukaryotic cells, no more than 10 microns across, which are biconcave, flattened discs that maximize surface area to volume for rapid gas diffusion in and out. RBCs outnumber leukocytes by about 1000 to 1 and are the components that make the blood viscous. A normal hematocrit is 5 million cells per cc of blood. Blood viscosity rises and falls in proportion to the number of RBCs present.

WBC Types

Leukocytes (White Blood Cells) Crucial in the body’s defense against disease These are complete cells, with a nucleus and organelles Able to move into and out of blood vessels (diapedesis) Can move by ameboid motion Can respond to chemicals released by damaged tissues Leukocytes White blood cells (WBCs) are less than 1 percent of total blood volume. Normally the white cell count is 4000-11,000 cells per mm3. Unlike red blood cells, leukocytes are complete, nucleated cells capable of dividing. White blood cells are capable of squeezing out of blood vessels (diapedesis) into the extracellular fluids and thus are found in the blood, the extracellular fluids around cells, and the accessory fluid system known as the lymph. White blood cells are responsible for gobbling up invading pathogens, destroying rogue cells, and making immunoglobulins (antibodies) to attack and clear foreign material from the body. White blood cells exhibit positive chemotaxis by responding to chemicals diffusing out of a site where cells are damaged. WBCs move by amoeboid motion up the diffusion concentration gradient to pinpoint areas of tissue damage. The inflammatory reaction, where extra fluid accumulates at the site of damage assists in WBC delivery. .

Leukocyte Levels in the Blood Normal levels are between 4,000 and 11,000 cells per millimeter Abnormal leukocyte levels Leukocytosis Above 11,000 leukocytes/ml Generally indicates an infection Leukopenia Abnormally low leukocyte level Commonly caused by certain drugs White blood cell number can double within the body in a few hours by massive reproduction to respond to an infection. A WBC count above 11,000 clls/mm3 is considered leukocytosis, an indicator of viral or bacteria infection. Leukocytosis can also be caused by bone marrow cancer (leukemia) or infectious mononucleosis. In these pathological conditions, WBCs are produced in large amounts in an immature form, making the body easy prey for infection. Leukopenia, an abnormally low WBC count can be caused by corticosteroids, anticancer agents, and AIDS. Leukocytes are classified into granulocytes and agranulcytes, based on the presence of visible granules in the cytoplasm

Types of Leukocytes Granulocytes Granules in their cytoplasm can be stained Include neutrophils, eosinophils, and basophils Granulocytes have granulated cytoplasm (visible with Wright's stain) and lobed nuclei. ｧ Neutrophils have multilobed nuclei and fine granules that show up with acidic or basic stains as an evenly stained pinkish cytoplasm. Neutrophils are voracious phagocytes at the sites of infection. ｧ Eosinophils have a blue-red nucleus under Wright's stain appearing like a telephone. Cytoplasmic granules appear as large brick-red spots. Eosinophils respond in allergenic reactions and infections by parasitic worms (flatworms, tapeworms, round worms). ｧ Basophils are the rarest leukocyte and contain very large histamine granules that stain dark blue. They release histamine to cause blood vessels to become leaky and to attract other WBCs to the inflammatory site. Figure 10.4

Types of Leukocytes Agranulocytes Lack visible cytoplasmic granules Include lymphocytes and monocytes Agranulocytes lack visible cytoplasmic granules and have spherical, oval, or kidney shaped nuclei. ｧ Lymphocytes have a large dark purple nucleus occupying most of the cell volume. There are only a bit bigger than RBCs in size and are found mostly in lymphatic tissues where they are involved with antibody production and pathogen lysis. Monocytes are the largest of WBCs with an indented nucleus. They look like big lymphocytes. Monocytes migrate into Figure 10.4

Hematopoiesis: Blood Cell Formation Occurs in red bone marrow All blood cells are derived from a common stem cell (hemocytoblast) Hemocytoblast (stem cell) differentiation Lymphoid stem cell produces lymphocytes Myeloid stem cell produces other formed elements Blood cells are formed in the process of hematopoiesis in red bone marrow (myeloid tissue). This tissue in adults is found in the flat bones of the skull and pelvis, the ribs, sternum, and proximal epiphyses of the humerus and femur. Each type of blood cells is produced in different numbers and is discharged into the blood only after they mature. All the blood cells (formed elements) arise from a stem cell called a hemocytoblast that lives in the red bone marrow. Development and differentiation differs based on the pathway that it commits to. Two general types of cell lines, the lymphoid and myeloid stem cell lines produce lymphocytes and all other classes, respectively.

Bleeding Disorders Thrombocytopenia Platelet deficiency Even normal movements can cause bleeding from small blood vessels that require platelets for clotting Hemophilia Hereditary bleeding disorder Normal clotting factors are missing or deficiency in Vit. K. Anemia is a condition where the oxygen-carrying ability of the blood is less than optimal. This can be caused by a low number of RBCs or abnormal/deficient amounts of hemoglobin per RBC. A lack of sufficient dietary iron, coupled with menstruation can cause this. Sickle cell anemia (SCA) is a genetic condition where abnormal hemoglobin is produced in RBCs and the oxygen-carrying capacity is lowered in these crescent-shaped erythrocytes. Chiefly occurring in black people and their descendents living in the malaria belt of Africa, SCA erythrocytes are poor hosts for the malaria parasite. Those people with sickle-cell trait are somewhat immune to malaria. Polycythemia is an excessive or abnormal increase in erythrocytes, resulting from bone marrow cancer or a response to living at higher altitudes where the air is thinner. Some athletes train at high altitudes, like Denver, Colorado, to increase the oxygen-carrying capacity of their blood within a week or so of their competitions at lower altitudes. The compromise is that polycythemia produces greater blood viscosity and slower circulation. mild hemophilia

Blood Groups and Transfusions Large losses of blood have serious consequences Loss of 15 to 30 percent causes weakness Loss of over 30 percent causes shock, which can be fatal Transfusions are the only way to replace blood quickly Transfused blood must be of the same blood group Self and Foreign Recognition of Antigens Blood transfusions are needed if the body loses over about 15% of its blood volume. Blood banks accept blood from living donors and store the blood for up to a month at 4oC. Blood transfusion cannot be safely done unless the antigenic properties of both donor and recipient blood are known. Antigens or substances protruding from a cell are recognized by the body as either normal or foreign. Foreign antigens that enter the body stimulate an immune response where antibodies are released to stick to (agglutinate) the antigen, lyse the cell it is attached to, and clear it from the body. The recognition of self versus foreign antigens is important in the thymus where white blood cells are selected based on the antibodies they produce. White blood cells, namely B and T cells each produce a specific type of antibody molecule that may or may not target host antigens. Those WBCs that make self-attaching antibodies are killed. Thus, in an adult, only foreign-recognizing WBCs and their antibodies circulate in the blood. When blood cells containing "foreign"- appearing antigens is transfused into a recipient, a huge immune reaction follows in which mass lysis of cells ensues. The glut of free hemoglobin may block the kidney tubules causing kidney failure, fever, chills, nausea, and vomiting. It can be life threatening.

Human Blood Groups Blood contains genetically determined proteins A foreign protein (antigen) may be attacked by the immune system Blood is “typed” by using antibodies that will cause blood with certain proteins to clump (agglutination) Blood Typing and Circulating Antibodies Both the donor and recipient blood cells therefore must be typed based on the antigens they contain; these must be compatible or alike in both individuals for a successful blood transfusion. The most important antigens among some 30 different membrane components are the ABO and Rh antigens. The blood of the recipient and available donors are typed by adding antibodies against certain antigens and looking for agglutination. It is therefore important that donor and recipient blood match with respect to ABO and Rh types.

Components of Blood of this Type Human Blood Groups There are over 30 common red blood cell antigens The most vigorous transfusion reactions are caused by ABO and Rh blood group antigens ABO Blood Groups and Alleles Components of Blood of this Type anti-A anti-B ABO Group The ABO blood groups involve A and B antigens found in the RBC plasma membrane. Carrying two genes for every trait, each person has up to two different ABO antigen proteins in their RBC membranes. IAIA or IAi genotypes produce only A protein in Type A blood. IBIB or IBi produce only B protein in Type B blood. IAIB yields Type AB blood and ii produces Type O blood (complete absence of any A or B antigen). Antibodies against any missing antigen (A or B or neither) are always present in the blood of the recipient and are the cause of immune reactions of mismatched blood transfusions. anti-B anti-A

Today’s procedures: Look at a Wright’s stain of whole blood, draw sketch, make a chart of struct. And funct. features of 3 cell types. Using blood slide, do a WBC (differential)- (see book pg. 644) and make a sketch of a neutrophil, eosinophil, basophil, lymphocyte, and monocyte (see pg. 645). Instructor will show how to make and read a hematocrit (on himself). Use his numbers to answer questions.