Blood: The River of Life Blood • Two components – Formed elements • Leukocytes (WBC) and platelets (buffy coat) equal less than 1% of blood • Erythrocytes (RBC) equal 45% of blood – Hematocrit = measure of RBC present – Plasma (fluid portion) = 55% of blood Blood Information • pH = 7.35 – 7.45 • Temperature = 38oC or 100.4oF – Slightly higher than body temp. • Approx. 8% of body weight – Males have 5-6 L while females have 4-5 L although amount depends on size • Color – Oxygen rich blood is scarlet red – Oxygen poor blood is dull or rusty red – Blood is heavier & more viscous than water Functions of Blood • Transport: Respiratory gases, hormones, cells and compounds • Maintenance Normal pH, Adequate fluid volume, electrolyte balance Functions of Blood • Prevention: – Blood loss through damaged vessels /clotting mechanisms • Defense: - Against pathogens using WBC and to help eliminate toxins • Absorb, distribute heat as part of temperature regulation. *overall helps with maintaining the organisms homeostasis. Erythrocytes • Structure: – Anucleate • Only survive ~120 days – Few organelles – Lack mitochondria • Don’t do aerobic respiration so don’t use up the oxygen that they are carrying – Biconcave shape • Allows for more surface area for diffusion of gases to take place RBC Proteins • Hemoglobin – 33% of cell weight – Carries oxygen on iron atoms RBC Proteins • Spectrin – Adds flexibility so cell can change shape without rupturing as it squeezes through capillaries • Misc. other proteins help with facilitating gas exchange and other functions RBC proteins Numbers of RBCs • Outnumber WBC 1000 to 1 • Women – 4.3 – 5.2 million RBC per mm3 of blood (about 1 small drop) • Men – 5.1 – 5.8 million RBC per mm3 of blood • # of blood cells compared to amount of plasma is major factor in blood viscousity – If blood is too viscous – heart must work too hard to pump it Anemia vs. Polycythemia Functions of RBCs • Major function is to carry oxygen • Single RBC contains ~250 million hemoglobin molecules each capable of carrying 4 oxygen atoms Hemoglobin • Values – Infant: 14-20 g / 100 ml – Male: 14-18 g / 100 ml – Female: 12-16 g / 100 ml • Protection of hemoglobin – Enclosed in RBC to prevent fragmentation which would increase blood viscosity Hemoglobin • Oxyhemoglobin – With O2 = bright scarlet red • Deoxyhemoglobin – W/o O2 = dull/rusty/dark red • Carbaminohemoglobin – With CO2 • Carboxyhemoglobin – With CO Hematopoiesis • Blood cell formation – Occurs in red bone marrow which is found in the ends of long bones and in flat bones • Hemocytoblasts convert to hemocytes – Cycle takes 3-5 days Stem Cells Erythropoiesis Red blood cell formation – Based on oxygen demands • Hypoxia: too few = oxygen deprivation • Too many (polycythemia) = increased blood viscosity *Two main types of polycythemia• Primary is inherited/congenital (incurable but treatable) Secondary is due to exposure to smoke, exposure to carbon monoxide & other risk factors HBP, Diabetes. • Hyperviscosity syndrome – Average production rate = 2 million/sec – Controlled hormonally • Based on level of available oxygen • Renal erythropoietic factor triggers erythropoietin production in kidney Erythropoiesis Erythropoiesis • Production depends on: – Fe, B12 vitamin, and folic acid • Necessary for DNA synthesis and hemoglobin synthesis • Small amounts are lost daily in feces, urine, sweat, and menstrual flow – 65% (4000mg) of iron stored is in hemoglobin – Free elemental iron is TOXIC so: • Iron is stored as ferritin or hemosiderin • Iron is transferred in the blood as transferrin Life Cycle of RBCs • After 120 days, the RBC is degraded and recycled • Hemoglobin is broken down to bilirubin – Goes to liver to be excreted – Liver damage can cause jaundice affecting many body organs – Bilirubin excess in brain causes kernicturus Life Cycle of RBCs Side Note: • Cancer of WBC – Leukemia Ex. Specifically “B” lymphocytes cancer is known as Waldenstrom’s Macroglobulinemia • Cancer of RBC – Multiple Myeloma Different ones affecting the different myeloid stem cells Leukocytes (WBCs) – body defense system • 4000 – 11,000 per mm3 • Complete cells with nuclei and various organelles Leukocyte Features • Diapedesis – Reach infection site by slipping into and out of blood vessels • Ameboid motion – Move through tissue spaces to reach location • Chemotaxis – Respond to chemicals released by damaged cells in order to locate damaged area Leukocytes-Granulocytes • Neutrophils • Basophils • Eosinophils Leukocytes • Know the features and function of each type of WBC: see notes • Granulocytes – contain specialized granules and lobed nuclei – Neutrophils • Most numerous • Active phagocytes – attracted to inflammation through chemotaxis • Numbers increase during bacterial & fungal infections • Produce white/yellow pus and snot – Basophils • Least numerous • Located in certain tissues – aka. Mast cells • Produce heparin & histamine to cause vasodilation and attract other WBCx to area of attack • Produce clear watery snot Leukocytes con’t • Eosinophils – 1-4% of WBCs – Located in intestinal & pulmonary mucosa and in dermis – Increase in number during • Parasitic worm infestations • Protozoal infestations • At end of allergy attack – produce chemicals to counteract allergic reactions • Produce greenish snot Leukocytes-Agranulocytes • Lymphocytes • Monocytes Leukocytes • Lack granules • Formed in bone marrow and then migrate to lymphatic tissues – rarely circulate in blood unless needed • 2 types Leukocytes • Lymphocytes – 2nd most numerous WBC – 20 to 40% – Play an immune system role • T-cells (several types) – Attack virus infected & tumor cells • B-cells (several types) – Produce antibodies (immunoglobulins) Leukocytes • Monocytes – Largest of WBCs – Very mobile, aggressive macrophages – Increase in number during chronic infections (such as tuberculosis) and act against viruses and bacteria in long term infections – Activate lymphocytes to start immune response Leukopoiesis • CSFs and interleukins stimulate • • • • production Activated in response to infections, toxins, tumor cells, etc. Granulocytes produced and stored in bone marrow as needed Granulocytes have short life span – die fighting invaders Agranulocytes may live days to years depending on type Plasma • • • • Straw colored, sticky fluid matrix 90% water 10% dissolved proteins, gases, wastes, etc. Plasma proteins produced by liver: know functions: – – – – Albumin Fibrinogen Alpha & beta globulins Gamma globulins • Homeostatic levels maintained by various organs Platelets (Thrombocytes) • Formed by megakaryocytes (stem cells) • Fragments of cells that clump together to form a seal at damaged BV locations • Not a complete cell – lack nuclei and organelles so short life span Clot formation Blood Volume Worksheet • Quickly complete the calculations on your Blood Volume Worksheet – Measure out the amounts using the colored water Steps of Hemostasis • Platelet plug formation – Normally, platelets and endothelium are both positively charged so they repel each other and the endothelial wall of BV – When endothelium ruptured, +platelets contact negative collagen fibers – Chemical changes cause platelets to swell and stick together and to the wall – Chemicals are released to attract more platelets to seal cuts – Platelet plug is formed – effective in sealing small vascular nicks Aspirin • Aspirin inhibits platelet plug formation and prolonged bleeding may occur – In small doses, it inhibits unecessary clotting thus preventing heart attacks & strokes • Aspirin is an anticoagulant Steps to Hemostasis • Vascular Spasms – Pain and serotonin release triggers vasoconstriction – More efficient when crushed than when it is a clean cut Steps to Hemostasis • Coagulation – blood clotting • Critical events that occur: – Thromboplastin released by injured tissue – interacts with prothrombin activator (PF3) – Which converts prothrombin to thrombin – Which joins fibrinogen molecules into a fibrin mesh – Which traps RBCs and pulls edges closer together Hemostasis (blood stopping) Hemostasis • More than 30 substances involved – Procoagulant – promotes clotting – Anticoagulant – inhibits clotting • Pathways – Intrinsic • Thromboplastin comes from platelets • 3-6 minutes for pathway – Extrinsic • Thromboplastin comes from injured tissue • 15 seconds for pathway Fibrinolysis (clot busting) Fibrinolysis • When normal cell regeneration begins, clot becomes unnecessary • Plasmin (clot buster) is released until clot is dissolved totally Factors that limit Clot formation • Dilution of factor – Normal blood flow keeps factors diluted • Impairment – Heparin in blood inhibits any clotting factors that have been activated but not used – See imbalance symbol page 586 • Molecular – Structural & molecular characteristics of endothelium & platelets Disorders of Hemostasis • Type I: Thromboembolytic conditions – undesirable clot formation – Thrombus: clot that develops in an unbroken blood vessel – Embolus: thrombus that breaks away from BV wall and floats freely in bloodstream • Either may block circulation to tissues beyond the occlusion and cause death to those tissues • Pulmonary embolism, stroke, heart attack Disorders of Hemostasis • Endothelial roughening: impairment of endothelial characteristics such as arteriosclerosis, severe burns/scar tissue, or inflammation may give platelets a place to cling and begin a thrombus • Blood stasis: slowing of blood flow particularly in immobilized patients does not keep clotting factors diluted Disorders of Hemostasis • Bleeding disorders: prevention of proper clot formation – Thrombocytopenia: platelet count under 50,000 per mm3 • Petechiae: small purplish blotches (bruises) caused by spontaneous bleeding from small BV all over body • Cause: damage to myeloid tissue (bone marrow): bone marrow cancer, radiation, certain drugs • Treatment: whole blood transfusion or in some cases platelet transfusion Disorders of Hemostasis • Impaired liver function – Little to no procoagulants produced – Causes: vitamin K deficiency, hepatitis, cirrhosis • Vitamin K is a fat soluble vitamin produced in your intestines by bacteria: liver produces bile which is necessary for fat absorption – No bile = no fat absorption = vitamin K deficiency = no procoagulant production – Treatment: Depends on cause Hemophilia • Hereditary X linked trait so usually affects males – Hemophilia A = factor VIII deficiency – most common – Hemophilia B – factor IX deficiency – Hemophilia C – factor XI deficiency • Symptoms: minor tissue trauma causes prolonged bleeding, bleeding into joint capsules after exercise or trauma • Management: clotting factor transfusion RBC & WBC disorders • See notes Blood Groups • RBCs contain antigens (glycoproteins) for cell recognition – 30 common varieties - over 100 "family antigens" – common antigens - ABO and Rh cause vigorous transfusion reactions – others mainly used for ID purposes (paternity, inheritance, etc. - only typed in cases of several transfusions (cumulative effect) • ABO blood groups – based on presence or absence of A or B antigens on RBCs – plasma antibodies act against antigens not present on that individual's RBCs – see chart Antigens & Antibodies Rh factor • Rh+ 85% of Americans - carry Rh antigen on RBC • Rh- don't have antigen on RBC • less severe transfusion reaction (hemolysis of donor RBCs) - doesn't usually occur until 2nd transfusion due to body's reaction time • can cause erythroblastosis fetalis (hemolytic disease of the newborn) if Rh- woman carries Rh+ baby – 1st baby is usually okay due to reaction time unless there was a bleeding problem during the pregnancy or a previous miscarriage or abortion. – 2nd baby will have its blood cells attacked by mother’s antibodies– Rhogam shot can prevent this if injected at 28 weeks of pregnancy and again right after birth. Transfusions • In case of blood loss, body tries to: – 1. reduce BV volume to maintain circulation to vital organs – 2. step up production of RBCs for replacement • • • • 15-30% loss - pallor & weakness over 30% - severe shock may be fatal substantial blood loss - whole blood transfusion Plasma, electrolyte solutions ( Ringer's solution) etc. can be used to increase blood volume while body steps up production of RBCs Transfusion Reaction • Mismatched RBCs antigens attacked by plasma antibodies • agglutination of foreign RBCs can: – clog small BV - reduce blood flow – lysed RBCs release hemoglobin into bloodreduced oxygen capacity - blocks kidney tubules and causes renal shutdown • Reactions: fever, chills, vomiting • Treatment: alkaline fluids to dilute hemoglobin, diuretics to increase urine flow to flush kidneys Agglutination Know the information contained in this chart Developmental Aspects • Embryonic – Day 28 of pregnancy – RBC in fetal circulation – By 7th month: red marrow is chief site of hematopoiesis – HbF – fetal hemoglobin • Greater ability to pick up oxygen • Replaced by HbA after birth • Immature liver may lead to physiological jaundice Developmental Aspects • Adulthood – Dietary deficiencies or metabolic disorders cause abnormalities in BC formation or hemoglobin production – Iron deficient anemia more common in women Developmental Aspects • Old age – Leukemia risk – Pernicious anemia • Stomach mucosa atrophies with age • Less intrinsic factor (located in lining of stomach – function is B12 absorption) • Less B12 absorption • Leads to pernicious anemia Diagnostic Blood Tests • • • • • • low hematocrit = anemia high fat level (lipidemia) = problems with heart disease blood glucose test – diabetes, hypoglycemia, hyperglycemia differential WBC indicates type of infection platelet count – thrombocytopenia – clotting problems complete blood count = CBC – see handout