14.1: Characteristics of Blood. A Centrifuged Blood Sample. Blood Composition. Clinical Application /7/2017. Chapter 14 Lecture Outline

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1 14.1: Characteristics of Blood Chapter 14 Lecture Outline See separate PowerPoint slides for all figures and tables preinserted into PowerPoint without notes. Blood: A type of connective tissue suspended in a liquid matrix Transports vital substances Maintains stability of interstitial fluid Distributes heat Amount of blood varies with body size, changes in fluid concentration, changes in electrolyte concentration, and amount of adipose tissue Blood is about 8% of body weight; adult blood volume is about 5 L. Copyright McGraw-Hill Education. Permission required for reproduction or display. 1 Blood cells: Form mostly in red bone marrow, and are called formed elements : Red blood cells (RBCs) White blood cells (WBCs) Platelets (cell fragments) 2 A Centrifuged Blood Sample In a centrifuged blood sample: 55% is plasma 45% is RBCs WBCs and platelets are <1% Percentage of RBCs is called the: Hematocrit (HCT) or Packed cell volume (PCV) 3 4 Blood Composition Clinical Application 14.1 Universal Precautions 5 Universal Precautions: A set of specific safety measures taken by healthcare workers, to prevent transmission of bloodborne infectious pathogens in the workplace Mainly used for HIV and Hepatitis B virus, but applies to others too Universal means that it is assumed that any patient may have been exposed to bloodborne pathogens It is estimated that 4-7% of new cases of infectious disease are transmitted by unsafe injections Precautions include: - Use of personal protective equipment (gloves, masks) - Use of fume hoods, sharps containers - Safe work-place practices, such as hand-washing 6 1

2 14.2: Blood Cells The Origin of Blood Cells Hematopoiesis: Formation of blood cells Blood cells originate in red marrow from hemocytoblasts or hematopoietic stem cells Stem cells can then: Give rise to more stem cells Give rise to more specialized or differentiated cells in response to hematopoietic growth factors: Lymphoid stem cells Myeloid stem cells Lymphoid stem cells then give rise to lymphocytes Myeloid stem cells give rise to all other types of formed elements: Red blood cells, other types of white blood cells, and platelets 7 8 Characteristics of Red Blood Cells Red blood cells (RBCs): Also called erythrocytes Biconcave disc shape One-third hemoglobin: Oxyhemoglobin (with O 2 ) Deoxyhemoglobin (without O 2 ) Lack nuclei and mitochondria Cannot divide Can produce ATP through glycolysis Red Blood Cell Counts Red Blood Cell Count = number of RBCs in a cubic millimeter (mm 3 ) or microliter (μl) of blood Typical ranges include: 4,700,000 6,100,000/μLin males 4,200,000 5,400,000/μL in adult females 4,500,000 5,100,000/μL in children RBC counts are useful in diagnosis of diseases and evaluation of their progress Changes in RBC counts reflect changes in blood s oxygen-carrying capacity 9 10 Red Blood Cell Production and Its Control Erythropoiesis: RBC formation Occurs in red bone marrow Low blood O 2 causes kidneys and liver to release EPO (erythropoietin), which stimulates RBC production A negative feedback mechanism Hemocytoblast erythroblasts reticulocytes erythrocytes Within a few days many new RBCs appear in the blood Dietary Factors Affecting Red Blood Cell Production Vitamin B 12 and folic acid: Required for DNA synthesis; necessary for the growth and division of all cells Iron: Required for hemoglobin synthesis

3 Types of Anemia Red Blood Cell Destruction Anemia: Condition in which the O 2 -carrying capacity of the blood is reduced, due to deficiency of RBCs or hemoglobin Iron-deficiency anemia Sickle cell disease Life Cycle of a Red Blood Cell RBC Destruction: Hemoglobin Breakdown Types of White Blood Cells White blood cells (Leukocytes, WBCs): Protect against disease WBCs are produced in red bone marrow, under control of hormones: interleukins and colony-stimulating factors There are 5 types of WBCs, in 2 categories: Granulocytes, which have granular cytoplasm, and short life span: Neutrophils Eosinophils Basophils Agranulocytes, which do not have noticeable granules: Lymphocytes Monocytes Neutrophils: Small, light purple granules in acid-base stain Lobed nucleus; 2-5 sections Also called PMNs, Polymorphonuclear leukocytes First to arrive at infection site Strong phagocytes 54% - 62% of leukocytes Elevated in bacterial infections Neutrophils

4 Eosinophils: Coarse granules; stain deep red in acid stain Bi-lobed nucleus Moderate allergic reactions Defend against parasitic worm infestations 1% - 3% of leukocytes Elevated in parasitic worm infestations and allergic reactions Eosinophils Basophils: Large granules; stain deep blue in basic stain Granules can obscure view of nucleus Release histamine to stimulate inflammation Release heparin to stop blood from clotting Less than 1% of leukocytes Similar to eosinophils in size and shape of nuclei Basophils Monocytes Lymphocytes Monocytes: Largest of the WBCs Spherical, kidney-shaped, oval or lobed nuclei Agranulocytes Leave bloodstream to become macrophages 3% - 9% of leukocytes Live for weeks - months Phagocytize bacteria, dead cells, debris 21 Lymphocytes: Slightly larger than RBCs; smallest WBCs Large spherical nucleus surrounded by thin rim of cytoplasm Agranulocytes T cells and B cells are major types; both important in immunity T cells directly attack pathogens, tumor cells B cells produce antibodies 25% - 33% of leukocytes May live for years 22 Functions of White Blood Cells Functions of White Blood Cells Diapedesis: WBCs can squeeze between the cells of a capillary wall and leave blood vessel; then migrate toward infection site Phagocytosis: Engulfing and digestion of pathogens; neutrophils and monocytes are most mobile and active phagocytes Inflammatory response: Reaction that restricts spread of infection; promoted by basophils, by secretion of heparin and histamine; involves swelling and increased capillary permeability Positive chemotaxis: Attraction of WBCs to an infection site, by chemicals released by damaged cells 23 Neutrophils respond to a bacterial invasion by accumulating in the infection site, and destroying the pathogens by phagocytosis. 24 4

5 White Blood Cell Counts White Blood Cell Counts White Blood Cell Count: A procedure used to count number of WBCs/mm 3 of blood WBC count is typically 3,500 10,500/mm 3 (or μl) of blood Leukocytosis: High WBC count (>10,500/ μl) Acute infections, vigorous exercise, great loss of body fluids Leukopenia: Low WBC count (<3,500/μL) Typhoid fever, flu, measles, mumps, chicken pox, AIDS, polio, anemia Differential WBC Count: Lists percentages of types of leukocytes Percentages may change in particular diseases: - Neutrophils increase during bacterial infections - Helper T-cells (a type of lymphocyte) decrease in HIV infection Clinical Application 14.2 Leukemia Leukemia is a cancer of white blood cells Classified as acute (symptoms appear suddenly & progresses rapidly), or chronic (begins more slowly, may remain undetected for months or years) Lymphoid leukemia: Cancer of lymphocytes produced in lymph nodes Myeloid leukemia: Cancer of granulocytes produced in red bone marrow Symptoms of leukemia: Excess number of WBCs, fatigue, headache, nosebleeds, fever, respiratory infections, bone pain, bruising, slow blood clotting Treatments include traditional cancer treatments (chemotherapy), drugs that target enzymes specific to cancer cells, bone marrow or stem cell transplants, refining diagnosis Platelets Platelets (thrombocytes): Cytoplasmic fragments of megakaryocytes (a type of stem cells in red bone marrow) Produced by hemocytoblasts in response to the hormone, thrombopoietin Hemocytoblast megakaryocyte thrombocytes Lack a nucleus, and are less than half the size of a RBC Platelet count: 150, ,000/μL of blood Help in hemostasis (stoppage of bleeding) in damaged blood vessels, by sticking to broken surfaces Release serotonin, which causes smooth muscles in walls of broken blood vessels to contract Cellular Components of Blood 14.3: Plasma Blood plasma: Clear, straw-colored Liquid portion of blood 55% of blood volume 92% water Contains organic and inorganic chemicals Transports nutrients, gases, hormones, and vitamins Helps regulate fluid and electrolyte balance and maintain ph

6 Plasma Proteins Plasma proteins are the most abundant dissolved substances (solutes) in plasma Typically not used as energy source Most important blood gases: Oxygen Carbon dioxide Gases and Nutrients Plasma nutrients: Amino acids Simple sugars Nucleotides Lipids: Fats (triglycerides) Phospholipids Cholesterol Nonprotein Nitrogenous Substances Nonprotein Nitrogenous Substances (NPNs): Molecules that contain nitrogen, but are not proteins In plasma, NPNs include: Urea: product of protein catabolism; about 50% of NPNs Uric acid: product of nucleic acid catabolism Amino acids: product of protein digestion Creatine: stores energy in phosphate bonds; regenerates ATP in muscles Creatinine: product of creatine metabolism BUN: blood urea nitrogen; indicates health of kidney (if the level is too high, this indicates that the kidney is not excreting urea in normal quantity, due to some type of impaired renal function) 33 Plasma Electrolytes Plasma contains a variety of ions called electrolytes, since they ionize in water, and can conduct electricity They are absorbed from the intestine or released as by-products of cellular metabolism Electrolytes found in blood plasma: Sodium Potassium Calcium Magnesium Chloride Bicarbonate Phosphate Sulfate Sodium and chloride are most abundant electrolytes : Hemostasis Hemostasis refers to the stoppage of bleeding Actions that limit or prevent blood loss include: Blood vessel (vascular) spasm Platelet plug formation Blood coagulation These mechanisms are most effective in small blood vessel injuries Vascular Spasm Vascular spasm: Stimulated by cutting or breaking a small blood vessel Smooth muscle in blood vessel contracts rapidly Slows blood loss very quickly, and ends of vessel may close completely Triggered by stimulation of the blood vessel wall, pain receptor reflexes Response lasts a few minutes, but effect continues for 30 minutes By that time, platelet plug has formed, blood is coagulating, and serotonin from platelets causes vasoconstriction

7 Platelet Plug Formation Platelet plug formation: Triggered by exposure of platelets to collagen Platelets adhere to rough surface to form a plug 37 Blood Coagulation Blood coagulation: Most effective mechanism of hemostasis Form blood clot in a series of reactions, in which each step activates next one; this is called a cascade Initiated by 2 different methods: Extrinsic or Intrinsic clotting mechanism Many chemicals used in coagulation are called clotting factors Vitamin K necessary for functioning of some of the clotting factors Coagulation depends on balance between procoagulants and anticoagulants Major event is conversion of soluble fibrinogen to insoluble threads of fibrin, which traps blood cells 38 Summary: Hemostatic Mechanisms Extrinsic Clotting Mechanism Extrinsic clotting mechanism: Triggered by blood coming in contact with tissues outside of blood vessels or damaged wall of blood vessel Damaged tissues release tissue thromboplastin (factor III), which is not found in blood Cascade begins, involving sequential activation of several clotting factors Thrombin converts fibrinogen into insoluble fibrin threads Fibrin threads stick to damaged blood vessel surfaces, and trap blood cells and platelets. This mass is a blood clot. This is an example of a positive feedback mechanism; once clotting begins, it promotes additional clotting Intrinsic Clotting Mechanism Blood Coagulation Intrinsic clotting mechanism: Can start without tissue damage Activated when blood comes in contact with foreign surface, such as collagen, in connective tissue, instead of endothelium of blood vessel wall Triggered by Hageman factor XII (found inside blood) As in the extrinsic clotting mechanism, this begins sequential activation of several clotting factors Results in the same way as extrinsic clotting mechanism, with formation of a fibrin mesh and a blood clot

8 Blood Clotting Mechanisms Clotting Factors Fate of Blood Clots After a blood clot forms, it retracts and pulls the edges of a broken blood vessel together while squeezing serum from the clot Serum = plasma minus fibrinogen and most clotting factors Platelet-derived growth factor stimulates smooth muscle cells and fibroblasts to repair damaged blood vessel walls Plasmin digests fibrin threads, and dissolves the blood clot A thrombus is an abnormal blood clot that forms in a blood vessel An embolus is a blood clot moving through the blood vessels Abnormal Blood Clot Formation Thrombosis: Blood clot in a vessel supplying a vital organ (brain, heart) Infarction: Death of tissues which have blocked blood vessels due to blood clot formation Embolism: Blood clot that travels, and then blocks a blood vessel in an organ (such as pulmonary embolism in lungs) Atherosclerosis: Accumulation of fat in arterial linings can sometimes cause abnormal clot formation; a common form of thrombosis 45 Normal artery Narrowed artery (plaque) 46 Clinical Application 14.3 Deep Vein Thrombosis Deep Vein Thrombosis: Clot formation due to pooling of stagnant blood, mainly in femoral or popliteal veins, or deep veins of pelvis Serious complication of DVT is a pulmonary embolism, in which blood clot travels through circulation, and lodges in a pulmonary blood vessel, resulting in loss of function in affected portion of the lung Occurs with prolonged period of immobility, such as airplane flight Symptoms of DVT: deep muscle pain, cramping, redness, swelling, and dilation of surface veins (phlebitis) Clot may break off hours or days after formation Prevention of Coagulation The smooth lining of blood vessels discourages the accumulation of platelets and clotting factors As a clot forms, fibrin adsorbs (latches onto) thrombin and prevents the clotting reaction from spreading Antithrombin inactivates additional thrombin, by binding to it and blocking its action on fibrinogen Some cells, such as basophils and mast cells, secrete heparin (an anticoagulant)

9 Factors That Inhibit Blood Clot Formation 14.5: Blood Groups and Transfusions In 1910, identification of the ABO blood antigen gene explained the observed blood type incompatibilities Today there are 31 different genes known to contribute to the surface features of RBCs determining compatibility between blood types Blood Antigens and Antibodies Antigen: Any molecule that evokes an immune response If immune system finds a foreign antigen in the body, it produces antibodies against the antigen Antibodies: Proteins that react against a specific antigen In an incompatible blood transfusion, donor red blood cells (RBCs) evoke an immune response in the recipient, and antibodies in the recipient s plasma agglutinate the donor RBCs Agglutination: Clumping of RBCs, which occurs when an antibody (in recipient s plasma) encounters its specific antigen (on donor RBCs) There are 33 known antigens on RBC membranes, but only a few can evoke a serious transfusion reaction Only the antigens of the ABO and Rh groups evoke serious transfusion reactions 51 From Science to Technology 14.1 Blood Typing and Matching: From Serology to DNA Chips Accurate blood typing and donor/recipient matching is essential to prevent blood rejection in a transfusion Human blood can be classified into about 31 major types, based on antigens (protein and carbohydrate molecules) on RBC membranes There are also many subtypes for each type Serology has been used for many years to determine blood types; based on identifying antigens through chemical testing; 97% accuracy New method of blood typing involves DNA blood typing, to determine exact combinations of gene variants; DNA Chips have a 99.8% accuracy rate 52 ABO Blood Group Blood Type Frequencies in the U.S. ABO Blood Group is based on the presence or absence of two major antigens on red blood cell membranes: Antigen A and Antigen B Antigens A and B are carbohydrates Antibodies are associated with some blood types; in general, a person produces antibodies against antigens that are not present on his/her RBC membranes

10 Antigens and Antibodies of the 4 Blood Types Agglutination 55 When RBCs come in contact with antibodies against them, they will agglutinate (clump together). 56 Compatible Blood Types for Transfusions Type 0 = Universal Donor: Type O lacks the A and B antigens, so type O RBCs could be donated to a person with any blood type. Often, when given to a person with a different blood type, only the RBCs are donated (since plasma contains antibodies). Type AB = Universal Recipient: Type AB blood lacks both Anti-A and Anti-B antibodies, so a type AB person can receive donor RBCs of any type 57 Rh Blood Group The Rh blood group was named for the rhesus monkey, in which it was first studied The group includes several Rh antigens or factors, but most important one is antigen D Rh positive: Presence of antigen D or other Rh antigens on RBC membranes Rh negative: Lack of the Rh antigens on RBC membranes Anti-Rh antibodies form only in Rh-negative individuals in response to the presence of red blood cells with Rh antigens The seriousness of the Rh blood group is evident in a fetus that develops the condition erythroblastosis fetalis or hemolytic disease of the newborn 58 Rh Incompatibility Inherited Blood Disorders