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The Cardiovascular System Ellen Black, Ph. D. Department of Neurological Sciences Office phone : 656-9397 E-mail : [email protected] 1 Overview of the Cardiovascular System The Cardiovascular system comprises the blood, the vessels which transport the blood, and the heart that pushes the blood through the system 2 Overview of the Cardiovascular System The heart is two pumps in one organ The RIGHT side pump collects oxygen-depleted, carbon-dioxide rich blood from the body through 2 venae cavae, and pumps it to the lungs through the pulmonary arteries. The LEFT side pump collects newly oxygenated blood from the lungs through pulmonary veins, and pumps it out to the body through the aorta. 3 Overview of the Cardiovascular System Blood passes to and from most organs of the body through the Systemic Circuit Arteries carry blood away from the heart Veins carry blood toward the heart In the systemic circuit, arteries carry blood that has high levels of oxygen and low levels of carbon dioxide; systemic veins returning from organs carry blood depleted in oxygen, with high CO2 content. 4 Overview of the Cardiovascular System Blood passes to and from the lungs through the Pulmonary Circuit Arteries carry blood away from the heart Veins carry blood toward the heart In the pulmonary circuit, pulmonary arteries carry blood to the lungs that still needs to be oxygenated, and is therefore oxygen-poor, CO2 rich. Pulmonary veins return freshly oxygenated blood to the left side of the heart. 5 Overview of the Cardiovascular System Topics : Blood Anatomy of Blood Vessels Anatomy of the heart The Conduction System The Cardiac Cycle Cardiodynamics Blood Flow and its Regulation Adaptation and Disorders of the Cardiovascular System 6 Blood Text reading: chapter 18 Classified as a connective tissue, but a fluid rather than solid Functions: – Transporting dissolved gases, nutrients, hormones, and metabolic wastes – Regulating pH and ion composition of interstitial fluids – Restricting fluid loss at injury sites (clotting reaction) – Defending the body against toxins and pathogens – Regulating body temperature by absorbing and redistributing heat 7 The Composition of blood Blood can be fractionated into 2 main components: Plasma Cell Fraction 8 Plasma • Approximately 46-63% of blood volume • 92% of plasma is water 9 The formed elements fraction contains red and white blood cells plus cell fragments called platelets 99.9% of cell fraction are RBC 10 Hemopoiesis = hematopoiesis The process of blood cell formation Occurs in the hollow center of bones (as “red marrow”) In fetal life, occurs mainly in liver and spleen With aging, fat takes over marrow cavity “yellow marrow” Hemocytoblasts are the stem cells that divide to form all types of blood cells; also called Pluripotent stem cells 11 Red Blood Cells = Erythrocytes • Carry oxygen to cells in the body • Erythrocytes account for slightly less than half the blood volume, and 99.9% of the formed elements • Hematocrit measures the percentage of whole blood occupied by formed elements – Commonly referred to as the volume of packed red cells 12 Erythrocyte Production Erythropoeisis = the formation of new red blood cells Process speeds up with in the presence of Erythropoietin (EPO = Erythropoiesis stimulating hormone) Blood doping strategies often involve this hormone RBCs pass through erythroblast and reticulocyte stages, during which time the cell actively produces hemoglobin A normal sample of peripheral blood usually does not contain nucleated RBCs : the nucleus and organelles are ejected after producing hemoglobin ~5 days to reticulocyte ~7 days to mature RBC Life span ~ 120 days 13 Red Blood Cells (Erythrocytes): Structure 14 Erythrocyte Structure Biconcave disc provides a large surface to volume ratio shape allows RBCs to stack, bend and flex RBCs lack organelles : NO NUCLEUS 15 Red Blood Cells travel single file through capillaries (the smallest diameter blood vessels) 16 Hemoglobin Hemoglobin molecules account for 95% of the proteins in RBCs Hemoglobin is a globular protein, formed from two pairs of polypeptide subunits – Two alpha subunits, 2 beta subunits – Each subunit contains one molecule of heme – Each heme has an iron (Fe) ion at its center – The iron reversibly binds an oxygen molecule – One hemoglobin molecule can bind up to 4 oxygen molecules • Damaged or dead RBCs are recycled by phagocytes 17 Life Span of Erythrocytes Approximately 1% of RBC are replaced per day Replaced at a rate of approximately 3 million new blood cells entering the circulation per second. Old or damaged RBC are removed from circulation by spleen before they hemolyze (rupture) Components of hemoglobin are individually recycled – Heme is stripped of iron and converted to biliverdin (greenish), then bilirubin (yellowish), which is processed by the liver – Globin protein fraction is broken down to amino acids, which are used to build other proteins – Iron is recycled by being stored in phagocytes, or transported through the blood stream bound to transferrin (free iron is toxic) 18 The Ultimate in Recycling 19 Disorders of Blood: Jaundice • Of the bilirubin formed in RBC breakdown, approximately 85% is removed from the blood and processed by the liver. • Failure of the liver to “keep up” with RBC breakdown or blockage of the bile ducts leads to a buildup of bilirubin in the blood. The bilirubin then diffuses out of the blood into tissues all over the body, giving the tissues a yellow color, readily apparent in the sclera of the eyes and the skin. 20 Disorders of Blood: Anemia A decrease in the oxygen-carrying capacity of blood Symptoms: lethargy, weakness, muscle fatigue, low energy Some types of anemia: • iron deficiency: hemoglobin is not functional without the iron • hemorrhagic: from hemorrhage, or severe blood loss; fewer RBC • anaplastic: bone marrow fails to produce enough RBC (radiation, immunologic diseases) Disorders of Blood: Sickle cell anemia Caused by a mutation of the amino sequence of the beta chain of hemoglobin. Without sufficient oxygen bound to it, hemoglobin molecules cluster into rods and force the cell into a stiffened, curved shape. These cells get stuck in capillaries, obstructing blood flow to the tissues, which causes pain and potentially damage to the organs. 22 Leukocytes : White Blood Cells • Lifespan varies by cell types; may be hours to years • Defend the body against pathogens • Remove toxins, wastes, and abnormal or damaged cells • Are capable of amoeboid movement and positive chemotaxis • Some are capable of phagocytosis 23 White blood cells can leave the bloodstream in response to chemical signals by squeezing through the vessel wall “diapedesis” Details to come in later lecture block 24 Types of White Blood Cells Granulocytes Named according to staining properties of cytoplasmic granules 50 to 70 % total WBC population (very mobile, 1st response to injury) phagocytes attracted to foreign compounds that have reacted with antibodies migrate to damaged tissue and release histamine and heparin Agranulocytes Lack cytoplasmic granules Leave circulation to become macrophages Immune system cells 25 The Complete Blood Count (CBC) One of the most common clinical tests performed Simple blood test measuring most parameters of blood • Hematocrit and hemoglobin concentrations • Platelet count • White blood cell count Includes counts of relative numbers of each of the types of white blood cell, providing valuable information relative to the type of infection e.g. High neutrophil counts indicative of bacterial infections e.g. High eosinophil counts indicative of allergy or parasitic infections 26 The Origin and Differentiation of Blood Cells note the pattern, not the details 1. Know common stem cell 2. Note the role of Colony Stimulating Factors (CSFs) 3. Know end products, not intermediate cells 27 Disorders of Blood: Leukemia • Leukemia is cancer of the white blood cell lines – Myeloid leukemia: abnormal granulocytes or other cells of marrow – Lymphoid leukemia: abnormal lymphocytes • Immature and abnormal cells enter circulation, invade tissues – Highly active cells, high energy requirements – May take over bone marrow, replacing normal cells • Loss of normal RBC, WBC and platelet formation results in anemia, infection and clotting problems normal leukemia 28 Platelets Pieces of a megakaryocyte membrane bound sacs of chemicals NOT CELLS Flattened discs Circulate for 9-12 days before being removed by phagocytes 29 Steps in Blood Clotting: Early role for Platelets 1. Vascular spasm Smooth muscle in the vessel wall contracts on injury, reducing the diameter of the vessel 2. Formation of a platelet plug a positive-feedback loop causing platelet aggregation to block the hole in the vessel wall. 30 Steps in Blood Clotting : Coagulation Phase 31 Steps in Blood Clotting : Coagulation Cascade 3. 4. Formation of a blood clot: the clotting cascade • Clotting can be initiated from damage within the vessel (intrinsic pathway) or around the vessel (extrinsic pathway) • Eventually, an enzyme called thrombin is activated, which converts soluble fibrinogen molecules in the blood to insoluble, loose fibrin threads. • The clot is a gel formed from a network of fibrin threads which trap blood cells and platelets. Clot Retraction Fibrin threads pull in on vessel wall, helping to plug the area and stopping blood loss. 32 Steps in Blood Clotting Eventual dissolution of clot : Fibrinolysis An inactive plasma enzyme called plasminogen is incorporated into the clot Chemicals in the clot (thrombin, tissue plasminogen activator (tPA) ) convert plasminogen to plasmin Plasmin digests fibrin threads and inactivates clotting mechanism Note: a genetically engineered version of tPA is now used to treat heart attacks and strokes caused by blood clots 33 There are MANY factors involved in the clotting process Do not memorize, but note that the liver is the source of many of these clotting factors 34 Excessive Clotting • Blood clots may form in the bloodstream in the absence of any injury. • A thrombus is an attached blood clot formed by platelets adhering to the blood vessel wall, often at sites of arterial disease. • If a piece of a thombus may detach and travel in the bloodstream as an embolus which may block blood vessels • There are many anti-clotting drugs available Heparin, Coumadin, tPA, Aspirin 35 Blood Types The surfaces of RBC are coated with glycoproteins and glycolipids which are capable of stimulating an immune response. These molecules (antigens) form the basis for the different blood groups. 36