Blood Physiology: Properties, Erythrocytes, Platelets - Physiology Notes PDF

Human Anatomy & Physiology II (PSIO202) Physical Properties of Blood & Erythrocytes Human Anatomy & Physiology II (PSIO202) Leukocytes & Thrombocytes  Objectives 1. Describe the origin and production of the various white blood cells. 2. List the characte...

Human Anatomy & Physiology II (PSIO202) Physical Properties of Blood & Erythrocytes Human Anatomy & Physiology II (PSIO202) Leukocytes & Thrombocytes  Objectives 1. Describe the origin and production of the various white blood cells. 2. List the characteristics and functions of white blood cells. 3. Categorize each of the white blood cell types on the basis of staining. 4. Describe the anatomy, physiology and relevance of phagocytosis. 5. Describe the structure, function and production of platelets. 6. Discuss the series of chain reactions that control blood loss after an injury. 7. Describe the series of events leading to platelet plug formation. 8. Diagram and compare and contrast the key elements of the extrinsic and intrinsic clotting pathways. Leukocytes a.k.a. White Blood Cells All WBCs (leukocytes) have a nucleus, but no hemoglobin Granular vs. agranular WBC’s… classification based on presence of cytoplasmic granules made visible by staining – granulocytes are neutrophils, eosinophils and basophils – agranulocytes are monocytes and lymphocytes Hematopoiesis-WBCs WBC Physiology WBCs are less numerous than RBCs – 1 WBC for every 700 RBC Leukocytosis is a high white blood cell count – microbes, strenuous exercise, anesthesia or surgery Leukopenia is low white blood cell count – radiation, shock or chemotherapy Only 2% of total WBC population is in circulating blood at any given time… the rest is in lymphatic fluid, skin, lungs, lymph nodes & spleen  WBC Physiology: Emigration WBCs roll along endothelium, stick to it & squeeze between cells. – adhesion molecules (selectins) help WBCs stick to endothelium – They are displayed near the site of injury – integrins found on neutrophils assist in movement through wall  WBC Physiology: Phagocytosis “cell eating” of bacteria Performed avidly by neutrophils & monocytes Performed weakly by eosinophils Phagocytosis involves: chemotaxis; adherence & ingestion; and destruction  Chemotaxis Tissue Blood in Attraction of phagocytic cells to fluid capillary the site of infection Chemicals released by the pathogen and/or the infected cell attract the phagocytes  Adherence & Plasma membrane Pseudopods Microbe Ingestion Receptor Adherence is the Phagosome attachment of the phagocyte to the pathogen’s membrane Ingestion is facilitated by enveloping pseudopodia, resulting in a phagosome  Destruction Plasma membrane Pseudopods Microbe Receptor Initiated when the phagosome fuses with a lysosome, resulting in Phagosome a “phagolysosome” Digestive enzymes Lysozymes and other destructive Fusion of chemicals from the lysosome lysosome destroy the membrane & internal and phagosome structures of the pathogen Digestion by Residual fragments of the dead lysosomal enzymes pathogen can be removed from the cell by exocytosis Residual body  Clinical Application: Use of a Bone Marrow Transplant Intravenous transfer of healthy bone marrow* Procedure – destroy “sick” bone marrow with radiation & chemotherapy – put sample of donor marrow into patient's vein for reseeding of bone marrow *success depends on histocompatibility of donor * & recipient* *can transplant stem cells instead of bone marrow *can be “autologous” Treatment examples: – leukemia, lymphoma, or multiple myeloma – sickle-cell or aplastic anemia – breast, ovarian or testicular cancer  Thrombocytes (a.k.a. platelets) platelets = cell fragments that circulate for 5-9 days, then die 2/3 of platelets circulate 1/3 of platelets reside in the spleen thrombus = a clot thrombosis = clot formation embolus = a circulating blood clot* hemorrhage = severe, uncontrolled bleeding http://www.ouhsc.edu/platelets/Platelet%20Pics/Platelets3.jpg  “Thrombocytopoiesis” Myeloid stem cells produce megakaryocytes, that have a diameter of ~160 m. Thrombopoietin, or TPO, causes fragments to slough off the megakaryocyte. 2,000-3,000 fragments, or platelets, enter the circulation Each platelet is ~ 2-4 m in diameter and ~ 1 m thick.  Hemostasis A series of reactions designed for stoppage of bleeding During hemostasis, 3 phases occur in rapid sequence: 1. Vascular spasms (immediate vasoconstriction in response to injury) 2. Platelet plug formation 3. Coagulation (blood clotting)  Hemostasis – Three steps Vascular Spasm – Step 1 – Occurs only in vessels with smooth muscle in wall – Reaction to injury – Reduces vessel diameter – Stops blood flow almost instantly – Effective only in small vessels Houben et al 2006 Vascular spasm of small blood vessels after application of angiotensin II  Platelet Plug Formation – Step 2 of Hemostasis Platelets NORMALLY do not stick to each other or to the endothelial lining of blood vessels… Upon damage to a blood vessel, platelets: – Stick to exposed collagen fibers – Are activated, allowing them to stick to one another – liberate thromboxane A2, serotonin and ADP*, which attract & activate still more platelets… *adenosine 5'-diphosphate – ADP makes platelets sticky – thromboxane A2 & serotonin cause cell contraction All of this results in the formation of a tight platelet plug. Blood Clotting (coagulation) – Step 3 of Hemostasis Coagulation = a set of reactions in which blood is transformed from a liquid to a gel – Very complex (about 30 substances) – 13 clotting factors (most from liver) – Has intrinsic and extrinsic pathways – Intrinsic pathway tends to be slower than the extrinsic pathway  Blood Clotting (coagulation)– Step 3 of Hemostasis The final three steps constitute the “common pathway”, which must be completed in order for effective clotting to occur 1. Once prothrombinase is activated, it converts prothrombin into thrombin 2. Thrombin has two main functions: Converts fibrinogen (soluble) to fibrin (insoluble, stable threads) Activates factor XIII, which stabilizes the fibrin network  Formation of Clotting Factors Prothrombin, fibrinogen, and factors V, VII, IX, and X are synthesized in the liver. Vitamin K is needed for the synthesis of factors II, VII, IX, & X. Vitamin K deficiency can lead to failure of blood clotting Individuals lacking factor VIII are hemophiliacs Fibrinolysis = clot breakdown Clots must be dissolved so that they do not enter the circulation as an embolus. The dissolution of a clot is known as fibrinolysis. Tissue plasminogen activator, thrombin and plasminogen all react to form plasmin, which then digests the fibrin strands and breaks the clot.  Objectives 1. Describe the important components of blood. 2. Know the general composition of plasma and formed elements. 3. Understand the major functions of blood. 4. Compare and contrast plasma and serum. 5. Describe the origin and production of formed elements in blood. 6. List the characteristics and functions of red blood cells. 7. Describe the structure and function of hemoglobin. 8. Understand how worn‐out or damaged erythrocytes are destroyed and/or recycled.  Body Fluids Cells of the body are serviced by 2 fluids: blood & interstitial fluid Nutrients & oxygen diffuse from the blood into the interstitial fluid & then into the cells Wastes move in the reverse direction Hematology is study of blood and blood disorders not responsible for  Figure 24.01 Intracellular fluid Digestive tract Bloodstream Tissue fluid Lymph Bloodstream  Composition of Blood 1. Plasma, a clear, straw colored watery liquid that consists of 91.5 % water, and 8.5 % solutes. 2. Formed elements, which are cells and cell fragments.  Blood Plasma Over 90% water ~7% plasma proteins – created in liver – confined to bloodstream 1. Albumins maintain blood osmotic pressure 2. Globulins (immunoglobulins) Antibodies which bind to foreign substances called antigens Form antigen‐antibody complexes Blood serum is blood 3. Fibrinogen for clotting plasma without fibrinogen and other clotting factors. ~2% other substances: – Electrolytes, nutrients, hormones, gases, wastes  Formed Elements of Blood Red blood cells ( erythrocytes or RBCs ) White blood cells ( leukocytes or WBCs ) – granular leukocytes neutrophils eosinophils basophils – agranular leukocytes lymphocytes = T cells, B cells, and natural killer cells monocytes Platelets (special cell fragments)  Erythropoietin (EPO) is a hormone which stimulates production of erythrocytes (RBCs) ‐ a process termed Erythropoiesis.  Platelets Thrombocytes The major function of platelets is blood clotting Platelets are irregular shaped cell fragments, with a diameter of ~2‐4 micrometers There are ~150,000‐400,000 platelets per microliter of blood. http://www.sciencephoto.com/media/139498/view Hematocrit  Hematocrit = % of blood occupied by RBCs Normal ranges: – Female 38‐46% (42% avg) – Male 40‐54% (46% avg) – Testosterone → EPO Anemia synthesis – Not enough RBCs (or hemoglobin) for proper O2 transfer Polycythemia – Having an excess of RBCs (over 65%) – Dehydration, tissue hypoxia, blood doping in athletes… Erythrocytes D=7.5 D = ~7.5  Erythrocytes (or red blood cells: RBCs) are shaped like biconcave discs this increases the surface area available for oxygen binding have an average diameter of ~ 8 m have no nucleus are easily deformed and can change shape – Are stacked (in rouleaux formation) in larger blood vessels as seen on the right – “parachute” shapes in small arterioles and venules – “bullet” shapes in capillaries they are filled with hemoglobin, ~10m ~6m a protein that carries oxygen. RBC “parachute” RBC “bullet”  Hemoglobin (Hb) Protein (“Molecule”) Hemoglobin is composed of: – “globins” 4 large protein chains (2 alpha and 2 beta chains) – a heme group (contained within each chain) The heme group: – is a porphyrin ring that surrounds a single iron molecule. Each iron in heme can bind one molecule of oxygen (O2). So each Hb can bind a total of 4 molecules of O2. The Heme Prosthetic Group  Functions of Hemoglobin Beta polypeptide chains (globins) Each hemoglobin molecule can carry 4 O2 molecules Oxygen is bound by hemoglobin (in RBCs in blood) in the capillaries of the lung and transported to the body’s cells by systemic circulation. Hemoglobin also transports 23% of the total CO2 produced in tissue cells; the CO2 binds to amino acids in the globin portion of hemoglobin (Hb), NOT with heme. Alpha polypeptide chains (globins)  Concentration of Hemoglobin in Blood 16 g/dL (g/100mL) of blood in men 14 g/dL (g/100mL) of blood in women The hematocrit and the hemoglobin level are diagnostic for anemia. http://www.anemia.org/patients/feature-articles/content.php?contentid=000482  Myeloid Erythropoiesis stem cell Erythropoiesis is RBC formation: formation – occurs in the red bone marrow. Hematopoietic – after birth, RBCs are formed from stem cell stem cells Proerythroblast – stem cells differentiate into proerythroblasts Erythroblast – proerythroblasts then become erythroblast then reticulocytes. Erythroblast – When a reticulocyte reaches maturity, hemoglobin is produced and the nucleus is ejected, resulting Erythroblasts in the formation of a mature Reticulocyte erythrocyte. http://www.immunopaedia.org.za/index.php?id=832 Erythrocyte (RBC)  Figure 18.06 Hematopoietic Colony-forming Mature Precursor cells blood cells stem cell (HSC) unit (CFU) Erythrocyte CFU Erythroblasts Reticulocytes Erythrocytes Hemopoietic Growth Factors Role: regulation of differentiation & proliferation of blood cells Erythropoietin (EPO) produced by kidneys; stimulates erythropoiesis (increases RBC precursors) Thrombopoietin (TPO) produced by liver; stimulates platelet formation Cytokines local hormones of bone marrow – stimulate proliferation in other marrow cells – colony‐stimulating factors (CSFs) & interleukins stimulate WBC production Figure 18.08  Medical Usage of Growth Factors Available through recombinant DNA technology – recombinant erythropoietin (EPO) is very effective in treating decreased RBC production of end‐stage kidney disease – other products given to stimulate WBC formation in cancer patients receiving chemotherapy which kills bone marrow – Thrombopoietin (TPO) helps prevent platelet depletion during chemotherapy  Life Cycle of Erythrocytes (RBCs) RBCs live only 120 days – wear out from bending to fit through capillaries – no repair possible due to lack of nucleus Worn out RBCs are removed by macrophages in the spleen & liver Breakdown products are recycled  Destruction and Recycling of RBCs Done by macrophages of the liver or spleen – globin portion broken down into amino acids & recycled – heme portion split into iron (Fe+3) & biliverdin (green pigment)  Destruction and Recycling of RBCs Iron(Fe+3) – transported in blood attached to transferrin protein – stored in liver, muscle or spleen (attached to ferritin or hemosiderin protein) – transported to bone marrow for use in hemoglobin synthesis Biliverdin (green) converted to bilirubin (yellow) – Bilirubin is secreted by the liver as part of bile, and bile is secreted into the intestine for use in digestion. – Bile breakdown products are excreted via kidneys & intestine (Bilirubin is converted in the large intestine into urobilinogen. Some urobilinogen is reabsorbed, converted into urobilin, and then excreted via the kidneys in urine.)  Life Cycle of Red Blood Cells Circulation for about 120 days 3 7 Reused for Amino protein synthesis Fe3+ Transferrin Globin acids 4 6 5 Fe3+ 2 Fe3+ Heme Ferritin Transferrin + Globin 9 Bilirubin + 1 Biliverdin Liver Vitamin B12 Bilirubin 11 10 + Red blood cell death Erythopoietin and phagocytosis Kidney Small Bilirubin intestine 13 8 Erythropoiesis in 12 Urobilin red bone marrow Macrophage in Urobilinogen Bacteria Key: spleen, liver, or 14 in blood red bone marrow Stercobilin Large in bile Feces intestine Urine