EVANGELISTA, GUTIERREZ

CIRCULATORY SYSTEM: BLOOD

11.1 FUNCTIONS OF BLOOD > The heart pumps blood through blood vessels that extend throughout the body> Blood helps maintain homeostasis in many ways.1. Transport of gases, nutrients and waste products. - Oxygen enters the blood in the lungs and carried to cells. Carbon dioxide, produced by cells, is carried in the blood to the lungs, from which it is expelled. - Blood transports ingested nutrients, ions and water from digestive tract to cells; waste products of cells to kidney for elimination. 2. Transport of processed molecules. - many substances are produced in one part of the body and transported in the blood to another part3. Transport of regulatory molecules. - blood carries many hormones and enzymes that regulate body processes4. Regulation of pH and osmosis. - buffers, which keep the bloods pH within its normal limits (7.35 7.45), are found in the blood. The osmotic composition of the blood is also critical for maintaining normal fluid and ion balance. 5. Maintenance of body temperature. - warm blood is transported from interior of the body to the surface, where heat is released from blood 6. Protection against foreign substances. 7. Clot formation. - protects against excessive blood loss when blood vessels are damaged - first step in tissue repair and restoration of normal function when tissues are damaged

11.2 COMPOSITION OF BLOOD > Blood- type of connective tissue that consists of a liquid matrix containing cells and cell fragments - makes up about 8% of total body weight > Plasma - liquid matrix - accounts for slightly more than half of the total volume > Formed elements - cells and cell fragments - account for slightly less than half of the total volume > Total blood volume in an average adult:- Females: 4 5 L; Males: 5 6 L

11.3 PLASMA > Plasma - pale yellow fluid - consists of 91% water, 7% proteins, 2% other components (ions, nutrients, gases, waste products, regulatory sibstances)- contains dissolved proteins: albumin, globulin, fibrinogen - plasma volume remains relatively constant > Albumin - makes up 58% of the plasma proteins- makes important contribution in the osmotic pressure of blood (although it results primarily from NaCl) > Globulins- makes up 38% of the plasma proteins - example: antibodies and complement (part of the immune system) - other albumin and globulins function as transport molecules because they bind to molecules, such as hormones, and carry them in the blood throughout the body - some are clotting factors> Fibrinogen - clotting factor that constitutes 4% of plasma proteins - activation of clotting factors results in the conversion of fibrinogen to fibrin, a threadlike protein that forms blood clots > Serum - plasma without clotting factors

11.4 FORMED ELEMENTS A. PRODUCTION OF FORMED ELEMENTS > Hematopoiesis - process of blood cell production - occurs in several tissues of the fetus- after birth, hematopoiesis is confined primarily to red bone marrow, but some wbc are produced in lymphatic tissues> Stem cells- a single population of cells where all the formed elements of blood are derived from - also called hemocytoblasts - differentiates to give rise to different cell lines > Cell lines- each ends with a with the formation of a particular type of formed element - development is regulated by specific growth factors> Growth factors - determine the types of formed elements derived from the stem cells and how many formed elements are produced

B. RED BLOOD CELLS - disk-shaped, with edges thicker than the center of the cell - biconcave shape increases surface area, which makes it easier for gases to move into and out of the RBC - can bend or fold around its thin center, decreasing its size and enabling it to pass more easily through smaller blood vessels - loses nuclei and most of organelles during development- unable to divide - live for 120 days in males; 110 days in females > Hemoglobin - pigmented protein; main component of a RBC - makes up 1/3 of cells volume and is responsible for the red color

b.1 Function > Primary function- transport oxygen from lungs to various tissues of the body and to help transport carbon dioxide from tissues to lungs - oxygen transport accomplished by hemoglobin, which consists of four protein chains and four heme groups- each protein called globin is bound to one heme, a red pigmented molecule - Heme each heme contains one iron atom, which is necessary for the normal function of hemoglobin each iron in this molecule can reversibly bind to an oxygen molecule - Hemoglobin that is bound to oxygen is bright red, those without is darker red - Hemoglobin is responsible for 98.5% of oxygen transported in the blood, 1.5% is dissolved in plasma- 2/3 of bodys iron is found in hemoglobin since it is necessary for oxygen transport - women need more dietary iron because they lose iron as a result of menstruation - other molecules can also bind to hemoglobin 1. Carbon Monoxide - binds to iron in hemoglobin 210 times more readily than does oxygen and does not tend to unbind - as a result, hemoglobin bound to this no longer transports oxygen - prolonged exposure to this causes nausea, headache, unconsciousness or death2. Carbon Dioxide - produced in tissues and transported in blood to lungs, where it is removed from the blood - CO2 transport includes bicarbonate ions, hemoglobin and plasma - 70% of CO2 in blood is transported in the form of bicarbonate ions - enzyme carbonic anhydrase, found primarily in RBC, catalyzes a reaction that converts CO2 and H2O into a hydrogen ion and a bicarbonate ion - can bind reversibly to the globin part of hemoglobin - 23% of the CO2 in blood is transported bound to hemoglobin or other blood proteins; remaining 7% is transported dissolved in plasma

b.2 Life History of Red Blood Cells - under normal conditions, about 2.5 million RBC are destroyed every second, new ones are produced just as rapidly - stem cells form proerythroblasts, which give rise to the RBC line- RBC are the final cells produced through a series of cell divisions - after each cell division, cell becomes a mature RBC - process of cell division requires B vitamins folate and B12, which are necessary for DNA synthesis- iron is required for the production of hemoglobin - lack of folate, B12, or iron can interfere with RBC production - RBC production is stimulated by low blood oxygen levels caused by low numbers of RBC, decreased or defective hemoglobin, diseases of the lungs, high altitude, inability of the cardiovascular system to deliver blood to tissues, and increased tissue demand for oxygen- low blood oxygen levels stimulate RBC production by increasing the formation and release of the glycoprotein erythropoietin primarily by the kidneys - Erythropoietin: stimulates red bone marrow to produce more RBC. Thus when oxygen levels in blood decrease, production of erythropoietin increases, which increase RBC production. - greater number of RBC increases bloods ability to transport oxygen- negative feedback mechanism returns blood oxygen levels to normal and maintains homeostasis by increasing the delivery of oxygen to tissues - high blood oxygen levels, less erythropoietin released, decrease in RBC production - when RBC become old, abnormal or damaged, they are removed by macrophages located in the spleen and liver- within the macrophage: globin broken down into amino acids (reused to produce other proteins) heme releases iron blood red bone marrow (used to produce new hemoglobin; therefore, iron is recycled- Bilirubin heme molecules are converted to bilirubin, a yellow pigmented molecule normally taken up by the liver and released into the small intestine as part of the bile if the liver is not functioning normally, or if flow of bile is hindered, bilirubin builds up and produces jaundice, a yellowish color to the skin after it enters the intestine, bilirubin is converted by bacteria into other pigments (some contributes brown color of feces, some contributes yellow color of urine)

C. WHITE BLOOD CELLS > White Blood Cells - spherical cells that lack hemoglobin - form a thin, white layer of cells between plasma and RBCs - larger than RBCs and each has a nucleus > Ameboid movement - WBC can leave the blood and travel by this movement through tissues - In this process, the cell projects a cytoplasmic extension that attaches to an object. Then the rest of the cells cytoplasm flows into the extension. > Functions1. Protect the body against invading microorganisms.2. Remove dead cells and debris from the tissues by phagocytosis. > Granulocytes - contains large cytoplasmic granules - 3 kinds: 1. Neutrophils - most common type of WBC - have small cytoplasmic granules that stain with both acidic and basic dyes - nuclei are commonly lobed (from 2 4) - usually remain in the blood for a short time (10 12 hours), move into other tissues, and phagocytize Microorganisms and other foreign substances - dead neutrophils, cell debris, and fluid can accumulate as pus at sites of infections 2. Basophils - least common WBC - contain large cytoplasmic granules that stain blue or purple with basic dyes - release histamine and other chemicals that promote inflammation - release heparin, which prevents the formation of clots 3. Eosinophils - contain cytoplasmic granules that stain bright red with eosin, an acidic stain- often have a two-lobed nucleus - involved in inflammatory responses associated with allergies and asthma - chemicals from eosinophils are involved in destroying certain worm parasites > Agranulocytes - contains very small granules that cannot be seen easily without the light microscope - 2 kinds: 1. Lymphocytes - smallest of the WBC - cytoplasm consists only of a thin, sometimes imperceptible ring around the nucleus - There are several types of lymphocytes and they play an important role in the bodys immune response. Their diverse activities involve the production of antibodies and other chemicals that destroy microorganisms, contribute to allergic reactions, reject grafts, control tumors, and regulate the immune system. 2. Monocytes - largest of the WBC - after they leave the blood and enter tissues, monocytes enlarge and become macrophages- Macrophages: >phagocytize bacteria, dead cells, cell fragments, and any other debris within the tissues>can break down phagocytized foreign substances and present the processed substances to lymphocytes, causing activation of the lymphocytes

D. PLATELETS> Platelets - minute fragment of cells , each consists of a small amount of cytoplasm surrounded by a cell membrane - produced in the red bone marrow from megakaryocytes- play an important role in preventing blood loss > Megakaryocytes - large cells - small fragments of these cells break off and enter the blood as platelets

11.5 PREVENTING BLOOD LOSS > Loss of blood can be minimized in three ways1. Vascular Spasm2. Platelet Plug Formation3. Blood clotting

A. VASCULAR SPASM Immediate but temporary constriction of a blood vessel that results when smooth muscle within the wall of the vessel contracts Produced by the nervous system reflexes Also produced by chemicals Thromboxanes Release by platelets Endothelin Released by endothelial cells

B. PLATELET PLUG FORMATION Accumulation of platelets that can seal up a small break in a blood vessel Very important because small tears occur in the vessels and capillaries everyday People who have low number of platelets develop hemorrhages Steps:1) Platelet Adhesion Platelets stick to the collagen exposed by blood vessel damage Mediated through von Willerbrand Factor A protein produced and secreted by blood vessel endothelial cells Forms a bridge between collagen and platelets by binding to platelet surface receptors and collagen2) Platelet Release Reaction Platelets release chemicals such as ADP and Thromboxane This activates other platelets and stimulates them to release ADP and Thromboxane as well This is an example of Positive Feedback Activated platelets express surface receptors called Fibrinogen receptors can bind to fibrinogen, a plasma protein3) Platelet Aggregation Fibrinogen forms bridges between the fibrinogen receptors of numerous platelets, resulting to a platelet plug

C. BLOOD CLOTTING For severely damaged blood vessels Blood clotting or coagulation results on the formation of a clot Clot Network of threadlike protein fibers called fibrin that traps blood cells, platelets and fluids Formation depends on a number of proteins found within plasma, called clotting factors. Stimulated only after injury. Stages:1) 2 ways to activate the Clotting factors First, inactive clotting factors come in contact with exposed connective tissue, or Chemicals, such as thromboplastin, are released from the injured tissues Activated clotting factors activate other clotting factors A series of reaction results in the formation of Prothrombinase, or Prothrombin Activator2) Prothrombinase converts an inactive clotting factor called Prothrombin to its active form, Thrombin3) Thrombin converts the inactive clotting factor Fibrinogen to its active form, Fibrin

Most clotting factors are manufactured in the liver, they require Vitamin K for their synthesis Many of the chemical reactions require Ca2+ Clotting process can be impaired by low levels of Vitamin K, low levels of Ca2+, low numbers of platelets or reduced synthesis of clotting factors due to liver dysfunction Sources of Vitamin K About half comes from diet Other half comes from bacteria within the large intestine

c.1 Control of Clot Formation Without control, clotting would spread from the point of its initiation throughout the entire circulatory system Blood contains anticoagulants, which prevent clotting factors from forming clots under normal conditions Antithrombin and Heparin inactivates thrombin, fibrinogen is not converted to fibrin, so no clot forms

c.2 Clot Retraction and Fibrinolysis Clot retraction is the process wherein a clot begins to condense into a more compact structure Platelets contain actin and myosin that contracts when platelets form small extension that attach to fibrin This leads to Clot Retraction Serum, which is plasma without the clotting factors, is squeezed out of the clot The vessel is repaired as fibroblasts move into the damaged area and new connective tissue forms. Epithelial cells around the would divide and fill in the torn area Fibrinolysis is the process wherein a clot is dissolved Plasminogen, an inactive plasma protein, is converted to Plasmin, its active form Thrombin and other clotting factors, and Tissue Plasminogen Activator (t-PA) stimulates the activation of plasminogen to plasmin Plasmin slowly breaks down the fibrin Streptokinase, a bacterial enzyme, and t-PA, produced through genetic engineering, have been used to dissolve clots

11.6 BLOOD GROUPING Transfusion is the transfer of blood or blood components from one individual to another Infusion is the introduction of a fluid or other than blood, such as a saline or glucose solution, into the blood Transfusion Reaction is characterized by clumping or rupture of blood cells and clotting within the blood vessels Antigens are found on the surface of RBCs Antibodies are found in the plasma Antibodies are very specific, meaning they can bind only to a certain antigen Agglutination, or clumping of the cells, is a result when antibodies bind to antigen and form molecular bridges that connect the RBCs together Combination of antigen and antibodies can also cause hemolysis or rupture of the RBCs Debris formed can block small blood vessels that results to tissue damage and death 2 Blood Groups ABO Blood Group Rh Blood Group

A. ABO BLOOD GROUP Used to categorize human blood; antigen and antibodiesBlood TypeAntigen Present(On RBC)Antibody Present(In Plasma)

Type AAntigen AAntibody B

Type BAntigen BAntibody A

Type ABAntigen ABNo Antibody

Type ONo AntigenAntibody A and B

Does not exist in equal numbers Antibodies against an antigen are produced only when the body is exposed to that antigen In blood transfusion: Donor is the one who gives the blood Recipient is the one who receives the blood Type O is the universal donor because it has no antigen to react with the antibodies of Type A, B and AB Transfusion of blood can still result to transfusion reactions because the antibody A or B of the donor can react with the antigen A or B or AB of the recipient This seldom occurs because the donors blood is diluted with large amounts of the recipients blood Type AB is the universal recipient because it has no antibody Transfusion Reactions can still occur because the Antibody of the donor may react with the antigen A or B of the recipient

B. RH BLOOD GROUP Named because it was first studied in the rhesus monkey People are Rh positive if they have certain Rh antigens on their RBCs and are Rh Negative if they do not have the Rh antigens on their RBCs ABO blood group and Rh blood group is expressed together (A-positive, B-negative) Rarest is the AB-Negative Rh antigens do not develop unless an Rh-negative person is exposed to Rh-positive RBCs Rh incompatibility is a major problem in pregnancy: If mother is Rh-negative and fetus is Rh-positive: If fetal blood leaks through the placenta and mixes with the mothers blood, the mother produces anti-Rh antibodies that cross the placenta and cause agglutination and hemolysis of the fetal RBCs This is called Hemolytic disease of the newborn (HDN) or Erythroblastosis fetalis There is no problem in the first pregnancy, the damage is in future pregnancies Rho(d) immune globulin (RhoGAM) contains antibodies against Rh antigens and can be used to prevent HDN

11.7 DIAGNOSTIC BLOOD TESTS 2 Types: Type and Crossmatch Complete Blood Count A. TYPE AND CROSSMATCH Determines the ABO and Rh blood groups to prevent transfusion reactions Crossmatch Donors blood cells are mixed with the recipients serum Donors serum is mixed with the recipient blood cells Transfusion can only occur if there is no agglutination in either match

B. COMPLETE BLOOD COUNT Analysis of blood that provides much useful information Consists of:1) RBCs Count2) Hemoglobin Measurement3) Hematocrit Measurements4) WBCs Count

b.1 Red Blood Count Performed electronically with a machine or manually with a microscope Male normal Red Blood Count: 4.6-6.2 million RBCs per microliter of blood Female normal Red Blood Count: 4.2-5.4 million RBCs per microliter of blood Erythrocytosis is an over abundance of RBCs

b.2 Hemoglobin Measurement Expressed in grams of hemoglobin per 100mL of blood Male normal hemoglobin: 14-18 grams per 100mL Female normal hemoglobin: 12-16 grams per 100mL A low hemoglobin measurement is a sign of anemia, which is either a reduced amount of RBCs or a reduced amount of hemoglobin in each red blood cell

b.3 Hematocrit Measurement Hematocrit is the percentage of the total blood volume that is composed of RBCs One way to measure hematocrit is to place blood in a capillary tube and centrifuge it Plasma at the top Buffy Coat (White blood cells and platelets) in the middle RBCs at the bottom In males, the RBCs account for 40-52% of the total blood volume In females, the RBCs account for 38-48% of the total blood volume Hematocrit measurement is affected by the number and size of RBCs because it is based on volume Average size of a Red blood cell is calculated by dividing the hematocrit by the red blood cell count

b.4 White Blood Count Measure the total number of WBCs in the blood Normally 5000-9000 WBCs per microliter of blood Leukopenia is a lower than normal white blood cell count resulting from decreased production or destruction of the red marrow Caused by radiation, drugs, tumors, viral infection, or a deficiency of the vitamins folate or B12 Leukocytosis is an overabundance of WBCs Bacterial infection often cause leukocytosis by stimulating neutrophils to increase in number Leukemia is the cancer of the red marrow characterized by abnormal production of one or more of the white blood cell types and this can also cause leukocytosis

C. DIFFERENTIAL WHITE BLOOD COUNT Determines the percentage of each of the five kinds of white blood cell Neutrophils = 60-70% Lymphocytes = 20-25% Monocytes = 3-8% Eosinophils = 2-4% Basophils = 0.5-1%

D. CLOTTING Bloods ability to clot can be assessed by the platelets count and the prothrombin time measurement

d.1 Platelet Count Normal platelet count is 200,000-400,000 platelets per microliter of blood Thrombocytopenia is a condition wherein the platelet count is greatly reduced resulting in chronic bleeding through small vessels and capillaries

d.2 Prothrombin Time Measurement Calculates how long it takes for the blood to start clotting Normally takes 9-12 seconds Determined by adding thromboplastin to whole plasma Thromboplastin is a chemical released from injured tissues to start the process of clotting Prothrombin time is officially reported as the Internation Normalized Ratio (INR)

E. BLOOD CHEMISTRY The composition of materials dissolved or suspended in the plasma can be used to assess the functioning of many of the bodys systems