Chapter 3 Blood
Chapter 3 Blood AGRI 313
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This 13 page Class Notes was uploaded by Angela Notetaker on Tuesday February 16, 2016. The Class Notes belongs to AGRI 313 at Fort Hays State University taught by Dr. Keener in Fall 2016. Since its upload, it has received 26 views. For similar materials see Anatomy & Physiology of Domestic Animals in Agricultural & Resource Econ at Fort Hays State University.
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Date Created: 02/16/16
Blood The functions of blood are generally related to: Transport of: nutrients, oxygen, carbon dioxide, waste products, hormones, heat dissipation, immune bodies Maintains fluid balance and pH balance in the body. General Characteristics Blood is composed of cells and plasma. ◦ Erythrocytes (red blood cells) ◦ Leukocytes (white blood cells) ◦ Platelets (thrombocytes) Plasma is the liquid portion of blood. ◦ The RBCs, WBCs, Platelets, and colloids are suspended in the plasma, and other transport substances are dissolved in the plasma. Blood Cells Hematocrit Measurement of the proportion of cells to plasma. ◦ Top portion occupied by plasma ◦ Middle portion occupied by buffy coat (leukocytes and platelets) ◦ Bottom portion occupied by erythrocytes and is known as the Packed Cell Volume (PCV). ▪ PCV is utilized in determining abnormalities. Blood Color Characteristics Hemoglobin within the erythrocytes imparts the red color. ◦ The degree of red coloration is directly related to the amount of oxygen saturating the hemoglobin. Plasma is yellow to colorless. ◦ The color of plasma is related to the presence of bilirubin. ◦ Bilirubin is a degradation product of hemoglobin. ▪ Certain species maintain darker colored plasma than others. Blood Volume Blood volume is generally 8% to 10% of the lean body weight. ◦ Blood volume cannot be measured directly because exsanguination results in only about 50% of total blood loss. ▪ The remainder is trapped in capillaries, venous sinuses, and other vessels. Blood pH is generally about 7.4. Leukocytes Classified as either: ◦ Granulocytes ◦ Agranulocytes Granulocytes Contain granules in the cytoplasm. ◦ Named according to staining of the granules. Three types: ◦ Neutrophils ◦ Basophils ◦ Eosinophils Agranulocytes Contain few if any granules in the cytoplasm. Two types: Monocytes Lymphocytes Granulocyte Life Span Leukocytes are circulated in the blood until the time they leave the circulation to perform their extravascular function. Granulocytes can be present in the blood for 6 to 20 hours and are constantly leaving. Granulocyte time varies in the tissue up to 2 to 3 days. ◦ Once granulocytes leave the blood, they do not normally return. Granulocyte Removal from the Body Granulocytes leave the body either from: ◦ Inflammatory sites or by way of the: ◦ Gastrointestinal ◦ Urinary ◦ Respiratory ◦ Reproductive tracts These organs are normally lined with neutrophils, which help prevent entry of organisms or foreign particles. Monocyte Life Span Monocytes have a circulation time of 24 hours or less, but can remain in the tissues for several months. Many monocytes become fixed macrophages in the sinusoids of the liver, spleen, bone marrow, and lymph nodes. ◦ This allows continued function in the blood and lymph. Lymphocyte Life Span Lymphocytes recirculate repeatedly from the blood to the tissues, to the lymph, and back to the blood. Lymphocytes consist of: T cells & B cells T cells are long-lived (100 to 200 days) B cells are short-lived (2 to 4 days) Memory T and B cells are very long lived (years) Leukocyte Function White Blood Cells serve as a defense mechanism against: ◦ Bacterial ◦ Viral ◦ Parasitic infections ◦ Proteins foreign to the body ▪ Each of the WBCs has a specific role in this broad function. Phagocytosis ◦ Involves the capability of the cell membrane to engulf particulate matter (bacteria, cells, degenerating tissue) allowing ingestion to occur within the WBC cytoplasm. Pinocytosis ◦ Involves the capability of the cell membrane to engulf and ingest extracellular fluid Phagocytosis 1. Neutrophil attacking bacteria. 2. Cell membrane engulfing the bacteria. 3. Bacterial ingestion into the neutrophil cytoplasm. Presentation of enzymatic lysosome to the ingested bacteria. 4. Enzymatic activity digests and neutralizes the bacteria. 5. Expulsion or exocytosis of waste material. Neutrophils Produced in the bone marrow Uptake both acidic and basic staining within their cytoplasmic granules. Azurophilic granules are lysosomes and supply enzymes to digest ingested bacteria, viruses, and Highly phagocytic Highly mobile Their numbers increase rapidly during acute infections. When neutrophils infiltrate an inflamed site, they phagocytize bacteria and cell debri. ◦ The life span is relatively short. ◦ Dead neutrophils and the associated liquid form pus, leading to the formation of an abscess. Neutrophil Movement Mechanism from Blood to an Inflammatory Site Chemotactic (chemically attracting)-degenerative products of inflamed tissue or bacterial cells diffuse through interstitial spaces to capillaries and venules Margination- chemotatic substances increase porosity of the vessels and provide adhesion of neutrophils to the endothelium. Diapedesis-neutrophils squeeze through the endothelial openings Ameboid movement-neutrophils proceed to the inflammatory site. Monocyte Agranulocyte Produced in the bone marrow Largest leukocyte seen on a stained smear. Occur in normal blood only to a limited extent Circulating monocytes phagocytize bacteria, viruses, and antigen-antibody complexes from the blood stream. ◦ Exhibit similar margination and diapedesis as neutrophils. On entering the tissues, they become Macrophages ◦ Large phagocytic cells Monocytes Monocyte enzyme systems degrade engulfed tissue debris from chronic inflammatory reactions. Monocyte numbers increase in chronic infections. ◦ Larger size and longer life span benefit effectiveness against chronic infections. Macrophages Kill phagocytized microbes with their acidic pH, bacteriostatic proteins, and degradative enzymes. They eventually predominate at the inflammatory site because of their longer life span. ◦ They are attracted to some organisms that neutrophils ignore. ◦ They phagocytize the cellular debri that remains when inflammation subsides. Eosinophils Produced in the bone marrow Uptake of acidic staining enhances red to reddish orange cytoplasmic granules. Granules contain enzymes that decrease allergic inflammatory reactions. Become more numerous in certain types of parasitism. Parasites are opsonized (attacked by antibodies) this immune response initiates eosinophil exposure stimulating granular content discharge onto the parasite surface. ◦ Enzymatic activity inflicts lethal damage. Basophils Produced in the bone marrow Uptake of basic staining Very rare in the blood Lack phagocytic capabilities Granules contain histamine, bradykinin, serotonin, and lysosomal enzymes. ◦ These substances initiate an inflammatory response. Initiate an inflammatory response through Immunoglobulin E (IgE) receptors. (allergies) Enhance allergic reactions. ◦ Rupture and release of granular contents causes local vascular and tissue reactions. Lymphocytes Originate from lymphoblasts which are lymphoid stem cells located in lymph tissue such as lymph nodes, spleen, tonsils, and various lymphoid clusters in the intestine and elsewhere. Involved in immune responses. Classified as T cells or B cells. Shortly before or after birth, stem cells are processed and differentiated in the thymus into T cells. Processing and differentiation for B cells occurs in the fetal liver, spleen, and bone marrow. T Cells T cells are involved in Cell-Mediated Immunity ◦ Involves the formation of large numbers of lymphocytes to destroy foreign substances (antigens). B Cells B cells are involved in Humoral Immunity ◦ Plasma cells produce large quantities of antibodies that inactivate foreign substances. Cell-Mediated Immunity Three different types of T cells: ◦ Cytotoxic T cells (killer cells) receptors bind to specific antigens, and cytotoxic substances are released into the foreign cell. ▪ Attack bacteria, viruses, tissue cells ▪ Attack cells of transplant organs ▪ Attack cancer cells ◦ Helper T cells (most numerous) assist, enhance, and intensify activation of cytotoxic T cells and B cells. ◦ Memory T cells (long lived) provide a response to the same antigen when exposed at a later date. Cell Mediated Immunity Cell Mediated Immunity kills cells that have become infected with a pathogen. Cell-mediated immunity is an immune response that does not involve antibodies but rather involves: ◦ The activation of macrophages and natural killer cells ◦ The production of antigen-specific cytotoxic T-lymphocytes ◦ The release of various cytokines Cell-mediated immunity is directed primarily at: ◦ Destroying virus-infected cells ◦ Intracellular bacteria and cancers ◦ It also plays a major role in delayed transplant rejection. T Cells are developed in the thymus. They enter the bloodstream and are carried by the circulation. Circulation carries them to a lymphoid organ, where they leave the bloodstream to migrate through the lymphoid tissue. After migration, T cells return to the bloodstream, and recirculate between the blood and peripheral lymphoid tissue until they encounter a pathogenic antigen. Humoral Immunity The term humoral immunity is a reference to the fact that this type of immunity is mediated by cells which float in the blood and lymph, or “humors” of the body. The component of the immune response involving the transformation of B cells into plasma cells that produce and secrete antibodies to a specific antigen. Humoral immunity originates in the B-cells. ◦ Specialized cells which come from the bone marrow, liver and spleen. B-cells are designed to produce antibodies when stimulated. (Plasma cells) ◦ They are stimulated most commonly by T-cells, which recognize antigens and trigger the production of antibodies by the B-cells. The B-cells (plasma cells) essentially turn into antibody factories in the blood, producing antibodies which attack as many pathogenic invaders as possible. B cells do not attack foreign substances directly. After exposure to an antigen, activated B cells proliferate and transform into: ◦ Plasma cells ◦ Memory cells (smaller number) Plasma Cells ◦ Produce large quantities of antibodies (immunoglobulins) that inactivate foreign substances. ▪ Antibodies accomplish inactivation through: Agglutination Precipitation Neutralization or lysis This type of immunity is a complement to cellular immunity, in which cells release toxins to: ◦ Kill unwanted invaders ◦ Attack the invaders directly to kill them The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. Complement System The complement system is made up of about 25 proteins that work together to assist, or “complement,” the action of antibodies in destroying bacteria. Complement also helps to rid the body of antibody-coated antigens (antigen-antibody complexes). Complement proteins, which cause blood vessels to become dilated and then leaky, contribute to: ◦ Redness ◦ Warmth ◦ Swelling ◦ Pain ◦ Loss of function that characterize an inflammatory response. Complement proteins circulate in the blood in an inactive form. When the first protein in the complement series is activated—typically by antibody that has locked onto an antigen—it sets in motion a domino effect. Each component takes its turn in a precise chain of steps known as the complement cascade. The end products are molecular cylinders that are inserted into—and that puncture holes in—the cell walls that surround the invading bacteria. With fluids and molecules flowing in and out, the bacterial cells swell, burst, and die. Other components of the complement system make bacteria more susceptible to phagocytosis or beckon other immune cells to the area. Complement reaction examples include: ◦ Opsonization ◦ Chemotaxis Opsonization ◦ Foreign substances are covered by antibody and become vulnerable to phagocytosis by neutrophils and macrophages Chemotaxis- Neutrophils and macrophages are attracted into the local region of the antigenic agent. ◦ Formation of other complement products results in: ▪ Lysis ▪ Agglutination ▪ Inflammation ▪ Activation of mast cells and basophils ◦ This produces a number of inflammatory effects in an effort to incapacitate the antigenic agent. Differential White Blood Cell Count A stained blood smear is observed and the different WBC types are counted and classified until a total of 100 has been counted. The number for each type is estimated as the percentage that is distributed in the blood. ◦ Leukocytosis-refers to an increase of leukocytes. ▪ Usually occurs in bacterial infections. ◦ Leukopenia-refers to a decrease in leukocytes. ▪ Usually associated with early stages of viral infections. ◦ Leukemia-is a cancer of WBCs and is characterized by leukocytosis. Erythrocytes Hemoglobin (Hb) ◦ The principal component of RBCs. ▪ Remainder of the erythrocyte is made up of water and stroma. ◦ Oxygen carrying capacity of the RBC ▪ Four heme groups and one globin molecule ▪ Each heme group contains an iron atom that reversibly binds to oxygen. ▪ One molecule of hemoglobin can carry four molecules of oxygen. ◦ Responsible for the red coloration Induced Hemoglobin Abnormalities Certain conditions alter the ability of hemoglobin to bind and carry oxygen. Nitrate poisoning ◦ Nitrate is converted to nitrite in the rumen. ◦ Nitrite oxidizes the ferrous iron of Hb to its ferric state. ◦ In the ferric state Hb becomes Methemoglobin. ◦ Methemoglobin lacks the ability to carry oxygen. ◦ Blood in the methemoglobin state maintains a chocolate brown coloration due to the lack of oxygen. Carbon monoxide poisoning ◦ Hemoglobin has an affinity for carbon monoxide approximately 200 times greater than its affinity for oxygen. ◦ Concentrations of carbon monoxide compete with oxygen and bind to hemoglobin. ◦ This binding results in carbonmonoxyhemoglobin. ◦ Carbonmonoxyhemoglobin prevents release of oxygen from hemoglobin to the tissues. ◦ Blood in the carbonmonoxyhemoglobin state is typically bright red. Erythropoiesis Erythropoiesis is the production of erythrocytes. ◦ Postnatal, during growth, and through adult life erythropoiesis predominantly occurs in the bone marrow. Erythrocytes are continually formed and destroyed. ◦ Approximately 35,000,000 erythrocytes are formed and destroyed in a 1000# horse each second. The rate seems to be regulated by tissue need for oxygen. ◦ Reduced tissue oxygen leads to hormonal kidney secretion erythropoetin. ◦ Erythropoetin stimulates the bone marrow to produce more erythrocytes ▪ Erythropoetin life span is approximately 1 day. ▪ Erythrocytes appear approximately 5 days later. Formation results in a biconcave disc shape. Erythrocyte Shape Erythrocytes typically exhibit a biconcave disk shape. Erythrocytes are tolerant of shape changes as they circulate. Advantages of a discoid shape: Larger surface area-volume ratio. Minimal diffusion distance. Greater osmotic swelling capability without threatening the integrity of the membrane. Erythrocyte Aging As erythrocytes age, several metabolic changes occur: ◦ The membrane becomes more rigid and fragile. ◦ The biconcave disk converts to a poorly deformable spherocyte. Erythrocyte Removal Some intravascular hemolysis occurs.(10%) The remainder of the aged RBCs are selectively removed by cells of the Mononuclear Phagocytic System. (90%) ◦ Mostly by fixed cells in the spleen, liver, and bone marrow. Erythrocyte Degradation Mononuclear Phagocytic System cells phagocytize aged erythrocytes. ◦ Hemolysis occurs inside the phagocytic cells Hemoglobin, proteins and membrane lipids are catabolized Iron and globin are separated from the heme. ◦ Globin is degraded into amino acids and are reutilized. ◦ Iron is stored in the MPS cells as Ferritin and Hemosiderin or ◦ Iron is transferred to plasma to combine with apotransferrin to become Transferrin ▪ Transferrin circulates to the bone marrow, iron is used for the synthesis of new hemoglobin. Protein and iron are removed from hemoglobin. Heme is converted to biliverdin (green pigment), then reduced to bilirubin (yellow pigment). ◦ Free bilirubin (water insoluble) is released into the plasma, binds to albumin and during transport through the liver conjugates with glucuronic acid to form bilirubin glucuronide (water soluble). ◦ Bilirubin glucuronide is secreted into the bile and absorbed into the intestine ◦ Bacteria in the large intestine reduce bilirubin glucuronide to urobilinogen ◦ Oxidized forms of urobilinogen are urobilin and stercobilin- these are the pigments that give feces a normal brown color. ◦ Some absorbed urobilinogen bypasses the liver, enters the circulation, and is excreted in the urine, giving urine its normal pigment as urobilin. Intravascular hemolysis occurs with hemoglobin initially binding to haptoglobin, then continuing as previously described. (slide 59) Extravascular disease 1. Liver disease compromises the formation of bilirubin glucuronide from free bilirubin combined with albumin, consequently continuing circulation in high concentration in the plasma and interstitial fluid. 2. Bile duct blockage results in bilirubin glucuronides spilling over into the plasma. Both of these situations result in increased content in the plasma producing a yellow color in the tissues known as icterus or jaundice. Intravascular disease Intravascular hemolysis of erythrocytes causes Hb to become bound to haptoglobin (plasma protein). ◦ This complex is rapidly removed by cells of the MPS, and Hb is degraded as in extravascular hemolysis. Excessive intravascular hemolysis (hemolytic disease) can occur, insufficient haptoglobin limits Hb binding leading to reddening of the plasma (hemoglobinemia) Hemoglobin is filtered at the kidney, but if the renal threshold for absorption is overwhelmed, reddening of the urine occurs (hemoglobinuria) Iron Metabolism Iron is ingested and reduced in the stomach and absorbed in the intestine. Absorption into the blood stream combines with apotransferrin (plasma protein) to form transferrin Within the bone marrow: ◦ Transferrin binds to receptors on forming erythrocytes ◦ Iron is released to be incorporated into the heme molecule. ▪ Apotransferrin is returned to the plasma. Iron absorption is regulated by: ◦ Amount stored in the body ◦ Rate of erythropoesis. Iron Storage Iron can be stored in all tissue cells especially the liver ◦ Ferritin ◦ Hemosiderin When liver stores are adequate, apotransferrin production decreases. When liver stores are depleted, apotransferrin production increases. Anemia A reduction in the number of erythrocytes and/or hemoglobin. Anemia can occur due to several causes: ◦ Blood loss ▪ Trauma ▪ Parasitism A common type of anemia involves iron deficiency in baby pigs. ◦ Rapid growth resulting in decreased erythropoiesis. ◦ Lack iron in the diet (sows milk). ◦ Iron deficiency causes an insufficient amount of hemoglobin production. Polycythemia Increased erythrocyte mass Relative Polycythemia-increase in red cell mass and decrease in plasma volume ◦ Shock ◦ Dehydration ◦ Diuretic and cardiac treatments Absolute Polycythemia-increase in red cell mass without a decrease in plasma volume. ◦ Hypoxemia ◦ Tumor Polycythemia vera-erythropoetin concentrations are normal or decreased ◦ Myeloproliferative disorder (increased bone marrow production) ◦ Very rare Hemostasis Blood vessel damage Platelets attach to the damaged surface and accumulate. Platelet plug forms. Coagulation occurs, formation of fibrin meshwork. Clot retraction occurs, and fibrinolysis begins. Connective tissue and endothelial cell growth repairs the vessel. Platelet-fibrin complex and other cell debris is removed. Vascular Endothelium The lining of the blood vessels. ◦ Basement membrane of collagen ◦ Fibronectin Intact endothelium, coagulation is prevented by: 1. negative surface charge repels negative charged platelets, 2. synthesis of platelet function inhibitors and fibrin formation inhibitors, 3. generation of fibrin degradation activators. Damaged endothelium disrupts the above three activities allowing platelet adhesion to occur. Platelet Adhesion Platelets attach to damaged endothelium forming pseudopods. ◦ Initial adhesion requires collagen and fibronectin ◦ Continued adhesion requires von Willebrand factor (vWF) and fibronectin from the platelets. Platelet Activation Agonist stimulator interacts with platelet surface receptors initiating intracellular messengers. ◦ Results in the release of Ca2+ due the messenger thromboxane (TXA2). ▪ Aspirin blocks the formation of thromboxane, which blocks Ca2+ mobilization from the granules to the cytoplasm. Platelet Release Reaction Increased intracellular Ca2+ causes granular contents to be secreted. Granular content is clustered in the center, and eventually extruded to the exterior of the platelet. Platelet Aggregation Granular contents expulsed onto the platelet exterior provides high concentrations of fibrinogen, fibronectin, and von Willebrands factor, factor V and other proteins. ◦ This enhances fibrin formation, adhesion, and conversion of prothrombin to thrombin leading to creation of a platelet plug. Clot Formation Prothrombin leads to thrombin formation Fibrinogen leads to fibrin formation Once this occurs the platelet plug becomes insoluble and stable preventing blood loss. Stabilization occurs in the presence of Ca2+. Clot Retraction Provided by action of the platelet contractile proteins, thrombosthenin, actin and myosin. Exposure of the proteins causes contraction of the clot, squeezing out serum, allowing for increased blood flow. Clot growth extends into the surrounding blood ◦ Clot growth stops when blood flow is enough to wash away thrombin and not allow it to attach to the existing fibrin. Fibrin Degradation New tissue growth repairs the damaged area Fibrinolysis occurs due to activation of plasminogen to plasmin. ◦ Tissue type plasminogen activator released from endothelial cells. Plasmin degrades the fibrin into fibrin degradation products. Fibrin degradation products are removed from the circulation by the Mononuclear phagocytic system. Normal Circulation Coagulation is prevented by the presence of antithrombin III. ◦ Blocks the action of thrombin converting fibrinogen to fibrin. Coagulation is prevented by the smooth endothelial lining of vessels. Coagulation is also prevented by the negative charge involving the endothelial lining. Heparin is an anticoagulant produced mast cells and maintains low blood levels. Anticoagulants in Blood Samples Chelating agents-bind calcium preventing the coagulation process. ◦ Trisodium citrate ◦ Sodium oxalate ◦ Ethylenediamine tetraacetic acid (EDTA) ◦ Heparin Plasma Noncellular liquid portion of anticoagulated blood. Contains: ◦ All of the coagulation factors ◦ Multiple proteins ◦ Predominantly water. Plasma proteins ◦ Albumin-formed in the liver ◦ Globulins-some are formed in the liver, gamma globulins are formed by lymph nodes and mucosal cells ▪ Gamma globulins contain antibodies called immunoglobulins-IgG, IgE, IgA, IgM, and IgD IgG provides immunity to the newborn IgE provides immune response to allergies or parasites IgA provides immune response to microorganisms in the mouth and gastrointestinal tract IgM provides activation of the complement system (humoral immunity) IgD provides clone formation of lymphocytes ◦ Fibrinogen-formed in the liver Plasma proteins, amino acids, and tissue proteins are in equilibrium. ◦ If one is depleted, the others compensate. Consequently, liver disease or starvation can have detrimental effects on overall body functions.
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