Blood = Transport Medium Components of the Circulatory System Heart = Pump Blood = Transport Medium Blood vessel = Passageways

Functions of Blood Transports: Defense: Maintains Homeostasis Nutrients Foreign organisms Electrolytes Injury/infection O2 & CO2 Waste Products Clotting process Hormones Body temperature Maintains Homeostasis

Components of Blood Blood is a mixture of cellular components suspended in plasma: 1. Erythrocytes (RBCs) 2. Leukocytes (WBCs) 3. Thrombocytes (platelets) Total Blood Volume: 8 % of body weight Plasma (water + dissolved solutes) 2.75 / 5.5 liters of blood is plasma (remaining is the cellular portion)

Blood vessel White blood cell Red blood cell platelet Plasma

Hematocrit “Packed Cells” RBCs heaviest – packed at bottom after centrifugation Average 45% for men / 42 % for women Important clinical diagnostic marker Anemia = Low percentage of erythrocytes Hematocrit – mostly RBCs b/c they are the most abundant type of blood cell (99%) Plasma = rest of blood not occupied by RBCs (55% of whole blood for males/ 58% for females)

Centrifuged Blood Sample

Separation of Components Plasma = Less Dense Platelets / WBC’s Hematocrit “Packed Cells” More Dense

Components of Plasma Blood plasma Consists of: Other components: Water 90% Plasma Proteins 6-8 % Electrolytes (Na+ & Cl-) 1% Other components: Nutrients (e.g. Glucose and amino acids) Hormones (e.g. Cortisol, thyroxine) Wastes (e.g. Urea) Blood gases (e.g. CO2, O2)

Functions of Plasma 1. Water: 2. Electrolytes: * Transport medium; carries heat 2. Electrolytes: * Membrane excitability * Osmotic distribution of fluid b/t ECF & ICF * Buffering of pH changes 3. Nutrients, wastes, gases, hormones: No function – just being transported 4. Plasma Proteins (See Next Slide)

Plasma Proteins Plasma Proteins: (albumins, globulins, fibrinogen) 1. Maintaining colloid osmotic balance (albumins) 2. Buffering pH changes 3. Transport of materials through blood (such as water insoluble hormones) 4. Antibodies (e.g. gamma globulins, immunoglobulins) 5. Clotting factors (e.g. fibrinogen)

3 Cellular Elements of Blood 1. Red Blood Cells 2. White Blood Cells 3. Platelets

Production of Formed Elements Hematopoiesis or hemopoiesis: Process of blood cell production Stem cells: All formed elements derived from single population Proerythroblasts: Develop into red blood cells Myeloblasts: Develop into basophils, neutrophils, eosinophils Lymphoblasts: Develop into lymphocytes Monoblasts: Develop into monocytes Megakaryoblasts: Develop into platelets

Hematopoiesis

1. RBC’S (Erythrocytes) Shape - a biconcave disc with large surface area Can change shape No Nucleus / organelles Contains hemoglobin Primary Function = Transport oxygen from the lungs to the cells of the body & assist with CO2 removal

Mechanism of Transport HEMOGLOBIN * 4 Heme Molecules = * 4 Oxygen Molecules *Oxygenated Hemoglobin Bright Red (systemic) *Deoxygenated Hemoglobin Blue (venous circulation) Minutia- Every erythrocyte has more than 250 million hemoglobin molecules- which means each RBC can carry more than a billion oxygen molecules!!!!

RBC’S (Erythrocytes) cont… Lack intracellular organelles necessary for cellular repair, growth, division Short Life Span (~120 days) Aged RBC Fragile - prone to rupture Ruptured RBC’s are destroyed in spleen Phagocytic WBC’s “clear the debris”

Formation of New RBC’s Ruptured cells must be replaced by new cells by a process called……… ..Erythropoiesis Secretion of the hormone erythropoietin New RBC’s (and platelets & leukocytes) are produced in the Bone Marrow We each have 25-30 trillion RBCs going through our vessels. Every second, we replace 2-3 million RBCs!

Figure 11-4

Too few, Too many Anemia – low hematocrit (below-normal oxygen-carrying capacity of the blood) Nutritional, pernicious, aplastic, renal, hemorrhagic, hemolytic Polycythemia- abnormally high hematocrit (too many RBCs in circulation) Primary, secondary Nutritional- dietary deficiency of factors needed for erythropoiesis Pernicious- inability to absorb enough ingested vitamin B12 from the digestive tract (deficiency of intrinsic factor) Aplastic- failure of the bone marrow to produce enough RBCs Renal- kidney disease (inadequate erythropoietin secretion) Hemorrhagic- loss of a lot of blood Hemolytic- rupture of too many RBCs (e.g. sickle cell disease) POLYCYTHEMIA- primary- erythropoiesis proceeds at an excessive, uncontrolled rate.- not subject to normal erythropoietin regulatory mechanism -makes blood super viscous Secondary- an appropriate erythropoietin-induced adaptive mechanism to improve blood’s oxygen carrying capacity in response to a prolonged reduction in oxygen delivery to the tissues. (normally in people at high elevations- where less oxygen is available in the atmosphere)

WBC’ s RBC’s

2. White Blood Cells (Leukocytes) Mobile units of body’s defense system: “Seek and Destroy” Functions: Destroy invading microorganisms Destroy abnormal cells (ie: cancer ) Clean up cellular debris (phagocytosis) 3. Assist in injury repair

5 - Types of WBC’s Each WBC has a specific function Granulocytes Agranulocytes Each WBC has a specific function

Blood Cell Origin and Production Bone Marrow All leukocytes ultimately originate from the same undifferentiated multipotent stem cells in the red bone marrow that also give rise to erythrocytes and platelets All new WBCs except for lymphocytes are produced in the bone marrow. Most new lymphocytes are produced by colonies of cells in lymphoid tissues, such as lymph nodes and tonsils. Circulation Figure 11-8

Neutrophils Eosinophils Basophils Types of WBC’s Polymorphonuclear Granulocytes Neutrophils Eosinophils Basophils

1. NEUTROPHILS * 50-70% of all leukocytes (most abundant of WBC’s) * Important in inflammatory responses * Phagocytes that engulf bacteria and Debris

2. EOSINOPHILS * 1-4% of the WBC's * Attack parasitic worms * Important in allergic reactions

3. BASOPHILS * 0.5% of the WBC's * Release histamine and heparin * Important in Allergic Reactions * Heparin helps clear fat from blood

Mononuclear Agranulocytes Types of WBC’s Mononuclear Agranulocytes 4. Monocytes 5. Lymphocytes (B and T cells)

4. MONOCYTES * 2-6 % of the WBC's * Exit blood (diapedesis) to become macrophages * Phagocytic = defend against viruses and bacteria

5. LYMPHOCYTES * 25-33 % of the WBC's * B-lymphocytes: Produce Antibodies * T-lymphocytes: Directly destroy virus- invaded cells and cancer cells B cells responsible for antibody-mediated (or humoral) immunity. – An Ab binds with and marks for destruction (by phagocytosis) the specific foreign matter that induced production of the Ab. T cells directly destroy their specific target cells by releasing chemicals that punch holes in the cell (process is called cell-mediated immunity)

Blood vessel White blood cell Red blood cell Platelets Plasma

3. Platelets (Thrombocytes) Platelets are produced by the bone marrow. They are not whole cells, but are fragments of extraordinarily large bone marrow-bound megakaryocytes. The hormone THROMBOPOIETIN (produced by liver) increases the # of megakaryocytes in the bone marrow, stimulating them to produce more platelets * Cell fragments bound to megakaryocytes * “Bud Off” and are released into the blood

Function of Platelets Stop bleeding from a damaged vessel * Hemostasis Three Steps involved in Hemostasis 1. Vascular Spasm 2. Formation of a platelet plug 3. Blood coagulation (clotting)

Steps in Hemostasis *DAMAGE TO BLOOD VESSEL LEADS TO: Vascular Spasm: Immediate constriction of blood vessel Vessel walls pressed together – become “sticky”/adherent to each other Minimize blood loss

Steps in Hemostasis 2. Platelet Plug formation: (figure 11-10) a. PLATELETS attach to exposed collagen b. Aggregation of platelets causes release of chemical mediators (ADP, Thromboxane A2) c. ADP attracts more platelets d. Thromboxane A2 (powerful vasoconstrictor) * promotes aggregation & more ADP Platelets will not adhere to normal vascular surfaces, but they do adhere to injured vessel surfaces when underlying collagen is exposed, forming a plug at the defect. The aggregated platelets release chemicals that induce other platelets passing by to become sticky and pile on top of the growing plug. Leads to formation of platelet plug !

(+) Feedback promotes formation of platelet Plug ! Figure 11-10 Adenosine diphosphate (ADP) release causes the surface of nearby circulating platelets to become sticky so that they adhere to the first layer of aggregated platelets. These newly aggregated platelets release more ADP, causing more platelets to stick etc etc- in a positive-feedback fashion. Platelet plug eventually broken because ADP release stimulates concurrent release of prostacyclin and NO from adjacent normal endothelium, which profoundly inhibit platelet aggregation- so platelet plug is limited to the defect (+) Feedback promotes formation of platelet Plug !

Final Step in Hemostasis Blood Coagulation (clot formation): “Clotting Cascade” Transformation of blood from liquid to solid Clot reinforces the plug Multiple cascade steps in clot formation Fibrinogen (plasma protein) Fibrin Thrombin

Thrombin in Hemostasis Factor X Figure 11-11

Clotting Cascade Participation of 12 different clotting factors (plasma glycoproteins) Factors are designated by a roman numeral Cascade of proteolytic reactions Intrinsic pathway / Extrinsic pathway Common Pathway leading to the formation of a fibrin clot !

Hageman factor (XII) X inactive active CLOT !

Clotting Cascade Intrinsic Pathway: Stops bleeding within (internal) a cut vessel Foreign Substance (ie: in contact with test tube) Factor XII (Hageman Factor) Extrinsic pathway: Clots blood that has escaped into tissues Requires tissue factors external to blood Factor III (Tissue Thromboplastin) Intrinsic pathway stops bleeding within cut vessel or clots blood outside the body EXTRINSIC pathway clots blood that has escaped into tissues

Clotting Cascade Fibrin : Threadlike molecule-forms the meshwork of the clot Entraps cellular elements of the blood forms CLOT Contraction of platelets pulls the damaged vessel close together: Fluid squeezes out as the clot contracts (Serum)

Clot dissolution Clot is slowly dissolved by the “fibrin splitting” enzyme called Plasmin Plasminogen is the inactive pre-cursor that is activated by Factor XII (Hageman Factor) (simultaneous to clot formation) Plasmin gets trapped in clot and slowly dissolves it by breaking down the fibrin meshwork Figure 11-15

Clot formation: Too much or too little of a good thing… Inappropriate clot formation is a thrombus (free-floating clots are emboli) An enlarging thrombus narrows and can occlude vessels Too little: Hemophilia- too little clotting- can lead to life-threatening hemorrhage (caused from lack of one of the clotting factors) Thrombocyte deficiency (low platelets) can also lead to diffuse hemorrhages

Blood Grouping Determined by antigens (agglutinogens) on surface of RBCs Antibodies (agglutinins) can bind to RBC antigens, resulting in agglutination (clumping) or hemolysis (rupture) of RBCs Groups ABO and Rh

ABO Blood Groups

Agglutination Reaction

Rh Blood Group First studied in rhesus monkeys Types Rh positive: Have these antigens present on surface of RBCs Rh negative: Do not have these antigens present Hemolytic disease of the newborn (HDN) Mother produces anti-Rh antibodies that cross placenta and cause agglutination and hemolysis of fetal RBCs

Diagnostic Blood Tests Type and crossmatch Complete blood count Red blood count Hemoglobin measurement Hematocrit measurement White blood count Differential white blood count Clotting

Blood Disorders Erythrocytosis: RBC overabundance Anemia: Deficiency of hemoglobin Iron-deficiency Pernicious Hemorrhagic Hemolytic Sickle-cell Hemophilia Thrombocytopenia Leukemia Septicemia Malaria Infectious mononucleosis Hepatitis