Erythrocytes, Blood Typing, and Hemostasis Erythrocytes Definition: Erythrocytes are red blood cells.Appearance: Biconcave shape, collapsed in the middle with a thick rim.Principal Functions Carry oxygen from the lungs to the tissues. Pick up carbon dioxide from the tissues and transport it to the lungs. Significance: Lack of red blood cells can lead to death in minutes due to oxygen deprivation.Characteristics Biconcave discs with a thick rim where most of the color is concentrated. Very flexible and able to change shape. Absence of Nucleus and Organelles: No nucleus or organelles, only some enzymes and hemoglobin.Significance of No DNA or Mitochondria No DNA: Means no cellular repair, limiting lifespan to about 120 days.No Mitochondria: Only anaerobic fermentation for ATP production; prevents consumption of carried oxygen.Structure and Composition Thick rim with concentrated hemoglobin. Very little cytoplasm, mainly in the rim. No organelles. Cell Membrane Components: Glycoproteins and glycolipids determine blood type.Cytoskeletal Proteins: Provide durability for bending through capillaries.Function of Red Blood Cells Major function is transport. Hemoglobin (Hb): Approximately 280 million molecules per red blood cell.Transports oxygen from lungs to tissues. Transports carbon dioxide from tissues to lungs. Carbonic Anhydrase: An enzyme that makes carbonic acid from carbon dioxide and water, important for gas transport and pH balance.C O < e m > 2 + H < / e m > 2 O ⇌ H < e m > 2 C O < / e m > 3 CO<em>2 + H</em>2O \rightleftharpoons H<em>2CO</em>3 C O < e m > 2 + H < / e m > 2 O ⇌ H < e m > 2 C O < / e m > 3 Hemoglobin Structure Four protein chains (globin):Adults: two alpha and two beta chains. Fetus: two alpha and two gamma chains. Fetal Hemoglobin: Gamma chains bind oxygen more strongly, allowing the fetus to draw oxygen from the mother's blood at the placenta.Globin binds to carbon dioxide. Four heme groups (non-protein moiety) with iron at the center; this is where the color comes from. Oxygen Loading and Unloading Oxyhemoglobin: Hemoglobin loaded with oxygen in the lungs, bright/ruby red.Deoxyhemoglobin (Reduced Hemoglobin): Oxygen unloaded in tissues, dark red.Carbaminohemoglobin: Carbon dioxide bound to globin in tissues; does not compete with oxygen and does not change blood color.Blood Analysis Red blood cell counts and hemoglobin concentration indicate blood's oxygen capacity.Hematocrit: Percentage of red blood cells in whole blood.Hemoglobin Concentration: Amount of hemoglobin in whole blood.Red Blood Cell Count: Number of red blood cells. Factors Affecting Red Blood Cell Values Values are generally lower in women.Androgens (e.g., Testosterone): Stimulate red blood cell production, higher in men.Menstrual Losses: Periodic blood loss in women.Body Fat: Hematocrit is inversely proportional to body fat; women have more body fat. Erythropoiesis (Red Blood Cell Production) About one million red blood cells produced per second. Average lifespan is about 120 days. Development takes three to five days. Process includes cell size reduction, mitosis, hemoglobin production, and removal of the nucleus and organelles. Steps of Erythropoiesis Hemopoietic Stem Cell: Common origin for red blood cells, white blood cells, and platelets.Colony Forming Units: First committed cells with receptors for erythropoietin (EPO).Erythropoietin (EPO): Hormone from kidneys, released when low oxygen is detected.Stimulates erythroblasts to multiply and synthesize hemoglobin. Reticulocytes: Immature red blood cells released into circulation with some endoplasmic reticulum.Mature in one to two days. Reticulocyte Count Normal range: 0.5% to 1.5% of red blood cells. Indicates the rate of red blood cell production. Nutritional Requirements Iron: Key nutritional requirement.Lost through urine, feces, and bleeding. Men need less than women. Low absorption rate. Iron Absorption: Converted to absorbable form, binds with gastroferritin, transported to blood, and picked up by transferrin.Iron Storage: Stored in the liver or red bone marrow.Toxicity of Free Iron: Number one fatal poisoning of children is multivitamins with iron.Conversion and Transport: Dietary iron converted in the stomach, picked up by a protein, and transported. In the blood, it binds to transferrin.Vitamin B12: Deficiency leads to pernicious anemia with misshapen red blood cells.Folic Acid, Vitamin C, and Copper: Needed for hemoglobin synthesis; vitamin C and copper act as coenzymes.Homeostasis of Red Blood Cells Negative feedback control. Hypoxemia: Low oxygen levels detected by kidneys.Erythropoietin (EPO) Release: Kidneys release EPO.Red Bone Marrow Stimulation: EPO stimulates red bone marrow, increasing red blood cell count.Stimuli for Erythropoiesis Low oxygen levels in blood. High altitude (lower partial pressure of oxygen). Increased exercise. Emphysema (lung damage impairs oxygenation). Negative Feedback Loop Low oxygen sensed by kidneys/liver, leading to erythropoietin secretion. Erythropoietin stimulates red bone marrow to produce more red blood cells. Increased red blood cells typically lead to more oxygen transport. Red Blood Cell Destruction One million red blood cells destroyed per second, balanced with production. Rupture occurs in the spleen or liver. Hemolysis: Rupture in the bloodstream is dangerous, releases hemoglobin, causes renal failure.Macrophages: In spleen and liver break down hemoglobin.Hemoglobin Breakdown Globin: Hydrolyzed into amino acids and recycled.Heme: Iron is pulled off and recycled. Pigment is excreted. Heme Pigment Conversion: Converted to biliverdin (green) then to bilirubin (yellow).Bilirubin Disposal: Spleen sends bilirubin to the liver, which secretes it in bile. Bile released into the small intestine. Bacteria in the large intestine convert pigments into urobilogens. Urobilogens converted to stercobilin (brown color of feces). Some urobilogens reabsorbed, converted to urochrome, and removed by kidneys (yellow urine). Life and Death of Erythrocytes Small intestine absorbs nutrients, sent to red bone marrow. Red blood cells produced for 120 days. Spleen and liver break down worn out red blood cells. Hemoglobin broken down by macrophages.Globin to free amino acids (recycled). Heme: iron is reused; pigment converted to biliverdin then to bilirubin, excreted in feces. Erythrocyte Disorders and Blood Typing Polycythemia Excess of red blood cells. Primary Polycythemia (Polycythemia Vera): Cancer of the erythropoietic cell in red bone marrow, hematocrit up to 80%.Secondary Polycythemia: Caused by another disorder (e.g., dehydration, emphysema, high altitude, physical conditioning).Dangers: Increased blood volume and viscosity, leading to high blood pressure; can cause embolism, stroke, or heart failure.Anemia Causes fall into three categories:Inadequate erythropoiesis or hemoglobin production. Hemorrhagic anemias (bleeding). Hemolytic anemia (red blood cell destruction). Inadequate Erythropoiesis Kidney Failure: Lack of erythropoietin production.Iron Deficiency Anemia: Insufficient iron to produce hemoglobin.Pernicious Anemia: Lack of vitamin B12, impairing hemoglobin production.Hemorrhagic Anemias Bleeding leads to loss of red blood cells. Acute or chronic (e.g., stomach ulcer). Hemolytic Anemia Red blood cells are destroyed. Consequences of Anemia Hypoxia and Necrosis: Low oxygen levels lead to tissue death.Reduced Osmolarity: Less reabsorption, producing tissue edema; blood pressure may also decrease.Low Blood Viscosity: Blood pressure drops, heart races to compensate, can cause cardiac failure.Sickle Cell Disease Hereditary defect mostly in people of African descent. Recessive allele modifies hemoglobin structure. Effect: Hemoglobin does not bind well with oxygen, red blood cells become rigid, sticky, and clump together, blocking small blood vessels.Consequences: Kidney or heart failure, stroke, extreme joint pain, and paralysis.Blood Types Antigens and Antibodies Based on interactions between antigens and antibodies. Antigen: Complex molecule on cell surface that activates an immune response (antibody generating).Antibodies: Proteins (gamma globulins) secreted by plasma cells (from B lymphocytes) in response to foreign matter.Agglutination: Antibodies bind to antigens, causing cells to clump together.Human Blood Groups Over 500 different antigens and at least 100 different blood groupings. ABO and Rh groupings are most important clinically due to severe transfusion reactions. Mismatched blood causes antibodies to agglutinate red blood cells, leading to hemolysis, hemoglobin release, and potential renal failure. ABO Group Determined by presence or absence of A and B antigens.Type A: A antigens. Type B: B antigens. Type AB: Both A and B antigens. Type O: Neither A nor B antigens. Most common is type O, rarest is type AB. Antibodies are anti-A (agglutinate A antigens) and anti-B (agglutinate B antigens). Antibodies appear 2-8 months after birth and reach maximum concentration by 8-10 years of age. Antibodies are in body fluids like plasma. ABO Group Review Type A: A antigens, anti-B antibodies (cannot receive blood with B antigens). Type B: B antigens, anti-A antibodies (cannot receive blood with A antigens). Type AB: Both A and B antigens, no antibodies (universal recipient). Type O: No A or B antigens, both anti-A and anti-B antibodies (can only receive type O blood). Testing Blood Type Purified antibodies are added to blood samples.Type A will clump with anti-A antibodies, but not anti-B antibodies. Type B will clump with anti-B antibodies, but not anti-A antibodies. Type AB will clump with both anti-A and anti-B antibodies. Type O will not clump with either anti-A or anti-B antibodies. Agglutination Each antibody can attach to several antigens on red blood cells simultaneously, causing clumping. Clumped red blood cells block small blood vessels, leading to hemolysis. Released hemoglobin blocks kidney tubules, causing acute renal failure. Universal Donor and Recipient Type O is the universal donor type, lacking A and B antigens. Type AB is the universal recipient type, lacking plasma antibodies. Rh Group Includes C, D, and E antigens, discovered in rhesus monkeys. D antigen is most reactive; positive if D antigen is present, negative if absent. Anti-D antibodies are not naturally present; develop only after exposure to positive blood. Hemolytic Disease of the Newborn Occurs if an Rh-negative mother has formed anti-D antibodies and is pregnant with an Rh-positive child. Maternal anti-D antibodies cross the placenta and attack the fetal red blood cells. Prevention: RhoGAM (anti-D antibodies) can be given to the mother to bind fetal D antigens and prevent her from forming anti-D antibodies.First pregnancy with a positive child usually has no issues, but subsequent pregnancies are at risk. Leukocytes Overview Least abundant formed elements (5,000 to 10,000 per microliter). Protect against infectious microorganisms and pathogens. Typically spend a few hours in the bloodstream before migrating to connective tissue, lymph nodes, and spleen. Retain organelles and nucleus. Granulocytes Possess specific granules containing enzymes and chemicals used against pathogens. Neutrophils Most abundant white blood cell, also known as polymorphonuclear leukocytes (PMNs). Nucleus is multi-lobed. Very antibacterial; important in the immune system. Eosinophils 2-4% of white blood cells. Numbers increase during parasitic infections and allergic reactions. Release enzymes to destroy large parasites. Basophils Less than 1% of white blood cells. Secrete histamine (vasodilator) to increase blood flow to injured areas. Produce heparin (anticoagulant) to prevent clot formation. Agranulocytes Lymphocytes T cells (T lymphocytes): Key component of the third line of defense in the immune system. B cells (B lymphocytes): Transform into plasma cells that produce antibodies. Natural killer (NK) cells. Monocytes Numbers increase during viral infections and inflammation. Transform into macrophages when they leave the bloodstream. Leukopoiesis Production of white blood cells. Originates from hemopoietic stem cells in the red bone marrow. Differentiates into colony forming units, which develop into specific types of white blood cells. Circulating white blood cells migrate to connective tissue. Leukocyte Disorders Leukopenia Low white blood cell count (below 5,000). Causes include radiation, poisons, and infectious diseases. Effects: Increased susceptibility to infection. Leukocytosis High white blood cell count. Indicates ongoing infection, allergic reaction, or disease. Leukemia Cancer of hemopoietic tissue. Characterized by high numbers of abnormal circulating leukocytes. Complete Blood Count (CBC) Includes several values:Hematocrit: Percentage of red blood cells (indicating polycythemia or anemia). Hemoglobin Concentration: Oxygen carrying capacity. Total Count for Red Blood Cells. Reticulocyte Count: Immature red blood cells, indicating rate of production. Differential White Blood Cell Count: Percentages of different types of white blood cells (lymphocytes, monocytes, neutrophils). Red Blood Cell Size and Hemoglobin Concentration: Helpful in diagnosing certain anemias, e.g., pernicious anemia (oversized, misshapen, pale red blood cells). Hemostasis Stopping bleeding to prevent death. Hemorrhaging is excessive bleeding. Three mechanisms work together: Vascular spasm, platelet plug formation, and coagulation (blood clotting). Platelets Small cell fragments of megakaryocytes. Normal count: 130,000 to 400,000 per microliter. Platelet Functions Secrete vasoconstrictors for vascular spasm, reducing blood loss. Stick together to form a platelet plug, sealing small breaks. Secrete procoagulants or clotting factors to promote clotting. Initiate clot-dissolving enzyme formation. Chemically attract neutrophils and monocytes to inflammation sites. Internalize and destroy bacteria. Produce growth factors that stimulate mitosis and vessel repair. Thrombopoiesis Platelet production. Stem cells develop receptors for thrombopoietin hormone and become megakaryocytes. Megakaryocytes live in the bone marrow next to blood sinusoids. Cytoplasm fragments split off to form platelets. Platelets circulate for 5-6 days. 40% are stored in the spleen. Mechanisms of hemostasis First one is vascular spasm. Second one is a platelet plug formation.Last one is coagulation the blood clot. Vascular Spasm Vasoconstriction of broken vessel cuts off blood supply, providing immediate protection against blood loss. Pain receptors, injury to smooth muscle, and serotonin release by platelets can cause vascular spasm. Intact vessels have smooth endothelium coated with prostacyclin (platelet repellent). Broken vessels expose collagen fibers. Platelets stick to collagen and then to each other, forming pseudopods and contracting to create a plug. Platelet degranulation releases chemicals that attract more platelets, creating a positive feedback cycle until the break is sealed. Coagulation Effective defense against bleeding. Converts soluble fibrinogen into insoluble fibrin threads. Clotting factors in plasma; one factor activates another in a reaction cascade (domino effect). Fibrinogen and clotting factors produced by the liver; liver damage impairs clotting. Coagulation Pathways Extrinsic pathway: Factors released by damaged tissue start coagulation quickly. Intrinsic pathway: Slower, started by platelets. Injured tissue activates both pathways simultaneously for fast coagulation. Calcium and vitamin K are essential for both pathways. Last Steps of Clotting Cascade Extrinsic or intrinsic pathway leads to prothrombin activator. Prothrombin activator converts prothrombin to thrombin. Thrombin converts fibrinogen to fibrin monomers which polymerize. P r o t h r o m b i n → P r o t h r o m b i n A c t i v a t o r T h r o m b i n Prothrombin \xrightarrow{Prothrombin \, Activator} Thrombin P r o t h r o mbin P r o t h r o mbin A c t i v a t or T h r o mbin F i b r i n o g e n → T h r o m b i n F i b r i n Fibrinogen \xrightarrow{Thrombin} Fibrin F ib r in o g e n T h r o mbin F ib r in Platelets and endothelial cells secrete platelet-derived growth factor to stimulate vessel repair. Fibrinolysis: Breaking down the blood clot by producing plasmin enzyme. Preventing Inappropriate Clotting Prostacyclin coating of blood vessels repels platelets. Thrombin is diluted and washed away by flowing blood. Natural anticoagulants: Heparin from basophils and mast cells; antithrombin from the liver. Clotting Disorders Hemophilia Deficiency of one or more clotting factors. Thrombosis Abnormal clotting in an unbroken vessel. Embolus: Anything that travels in the blood and blocks the blood vessels, causing tissue death and infarction.Stroke (brain). Myocardial infarction (MI, heart attack). Pulmonary embolism (lungs). Clinical Management of Blood Clotting Vitamin K antagonists (e.g., warfarin) tie up vitamin K to prevent formation of clotting factors. Aspirin suppresses one of the clotting factors. Other anticoagulants: Medicinal leeches and snake venom.