Hematology PDF

HEMATOLOGY BLOOD A fluid connective tissue with erythrocytes, leukocytes, platelets suspended in plasma General Functions of Blood Transportation of dissolved gases, nutrients, hormones, and metabolic wastes. Regulation of the pH and ion composition of interstitial fluids. Gen...

HEMATOLOGY BLOOD A fluid connective tissue with erythrocytes, leukocytes, platelets suspended in plasma General Functions of Blood Transportation of dissolved gases, nutrients, hormones, and metabolic wastes. Regulation of the pH and ion composition of interstitial fluids. General Functions of Blood (cont’d) The restriction of fluid losses at injury sites. Defense against toxins and pathogens. The stabilization of body temperature. Plasma Proteins: Albumins (55-60%) maintain osmotic pressure of plasma All plasma proteins contribute toward maintaining osmotic pressure of plasma but Albumins contribute the most as they are the most abundant plasma proteins. Transport fatty acids, thyroid & some steroid hormones & other substances Plasma Proteins: Globulins (35-38%) ▫ Antibodies/Immunoglobulins (IgG, IgE, IgD, IgM, IgA) ▫ Transport globulins bind small ions, hormones and compounds that may be lost at the kidneys or that have very low solubility in water (Eg. thyroid-binding globulin, transferrin, apolipoproteins and steroid-binding protein) Plasma Proteins: Fibrinogen (4-7%) ▫ Forms fibrin during the clotting of blood ERYTHROCYTES (Red Blood Cells) Functions 1. Transport of Oxygen  Contains haemoglobin to which O2 binds reversibly  O2 binds to the haem component of Hb 2. Transport of carbon dioxide on a small scale (23%)  CO2 binds to protein portion of Hb Erythrocyte Structure Biconcave, thin, contain Hb, devoid of nucleus and other organelles Diameter of 7.2 – 8.4 µm Edge thickness 2.31 – 2.85µm Central region thickness 0.45 – 1.16µm Erythrocyte Structure & Function Large surface area to volume ratio than spherical cell ▫ Allows for efficient diffusion of oxygen across the cell http://corescience.blogspot.com/2011_02_01_archive.html Erythrocyte Structure & Function RBCs able to form stacks (Rouleaux) in small capillaries ▫ Prevents individual cells from bumping the walls and banging together, and forming logjams that could restrict or prevent blood flow http://www.normanallan.com/Med/blood%20flow.htm Erythrocyte Structure & Function RBCs are flexible and can squeeze through capillaries of 4µm diameter Erythrocyte Structure & Function Lacks most organelles Allows more Hb to fit into cells 250 million Hb molecules in each RBC Blood Type  Blood type is determined by the presence of antigens (agglutinogens) on the plasma membranes of RBCs  Antibodies (agglutinins) are present in blood serum against foreign agglutinogens  Agglutinogens and Agglutinins are genetically determined and present throughout life Agglutinogens: Specific surface antigens on RBC plasma membranes They are integral membrane glycoproteins or glycolipids Blood Group Systems Each of these systems have several antigens ABO MNS P RHESUS LUTHERAN KELL LEWIS DUFFY KIDD ABO Blood Typing System  There are two antigens classified in the ABO Blood Typing System:  1. A antigen 2. B antigen ABO Blood Types based on antigens (agglutinogens) Type A Blood – A antigens only Type B Blood – B antigens only Type AB Blood – A and B antigens Type O Blood – neither A nor B antigens ABO Blood Types Antibodies (agglutinins) The Blood Plasma contains antibodies Two types of antibodies in the ABO system ▫ 1. anti-A antibodies ▫ 2. anti-B antibodies Antibodies attach to the antigens on foreign RBCs causing Agglutination and lysis of RBCs Agglutination of RBCs by Antibodies Hemolysed RBCs  When an antibody meets its specific surface antigen RBCs agglutinate and may even hemolyze The clumps and fragments formed can plug or rupture blood vessels in the kidneys, lungs, heart or brain  Agglutination vs No Agglutination of RBCs http://academic.kellogg.edu/herbrandsonc/bio201_McKinley/f21-7a_abo_blood_types_c.jpg  Rhesus Blood Typing System Antigens: The Rhesus antigen/Rhesus factor/D antigen is the only antigen in this system. It was first discovered in the Rhesus monkey Rhesus Blood Typing System There are 2 blood types in this system: 1. Rhesus Positive (Rh+)  Indicates the presence of the Rh surface antigen or Rh factor 2. Rhesus Negative (Rh-)  Indicates the absence of the Rh antigen Rhesus Blood Typing System When blood type is recorded, the term Rhesus (Rh) is omitted and the data reported as for eg. O negative (O-) or A positive (A+) Rhesus System Antibodies Only the Anti-Rhesus Antibody exists in the Rhesus System Rhesus System Antibodies The Rhesus positive blood type has no anti- Rhesus antibodies The Rhesus negative blood type ▫ Only develops Anti-Rhesus Antibodies after sensitisation ▫ Sensitisation occurs when Rh(-) blood is exposed to Rhesus antigens during blood transfusions and during pregnancy involving a Rh(-) mother and Rh(+) foetus Rhesus Incompatibility occurs when: A Rh negative person is transfused with Rh positive blood A Rh negative woman becomes pregnant with a Rh positive fetus Rhesus Incompatibility During Pregnancy Erythroblastosis fetalis Hemolytic Disease of the Newborn (HDN) ▫ Anti-Rh antibodies destroy fetal red blood cells causing a severe anaemia and jaundice ▫ Increased demand for blood cells forces immature RBCs to enter circulation from bone marrow ▫ Infant will probably die without a blood transfusion RhoGam Prevents HDN RhoGam Prevents HDN  Maternal production of anti-Rh antibodies can be prevented by administering RhoGam (anti-Rh antibodies) in the last three months of pregnancy and during and after delivery  RhoGam also given after miscarriage and abortion  These antibodies will destroy any fetal RBCs that cross the placenta before they can stimulate an immune response (prevents sensitization of the mother) Transfusion Compatibility Before a recipient receives a transfusion, compatibility testing between donor and recipient blood must be done to prevent transfusion reactions Compatibility testing may involve: ▫ Determining blood type  Mixing drops of blood separately with solutions of Anti-A, Anti-B and Anti-Rh antibodies ▫ A Cross-match Test  Mixing a sample of donor blood with recipient blood Blood Typing Test Blood Type Test Results Cross Match Test - Samples of donor and recipient blood mixed No agglutination/Compatible Agglutination/ Not Compatible Blood Compatibility blood_types_in_ja http://www.nbts.gov.jm/pages.php?id=6 LEUKOCYTES (White Blood Cells) Migrating Cancer Cell (yellow) attacked by immune cells Immune cell lower right delivers “kiss of death.” LEUKOCYTES (White Blood Cells) Lack haemoglobin Mobile units of immune system Remove toxins, wastes and abnormal or damaged cells 1 µl of blood contains 5000 – 10,000 WBCs ( 1 µl of blood contains 4.2 – 6.3 million RBCs) Most WBCs are located in connective tissue proper or lymphoid organs Red Blood Cells White Blood Cells Types of White Blood Cells Granulocytes Agranulocytes ▫ Neutrophils ▫ Monocytes ▫ Eosinophils ▫ Lymphocytes ▫ Basophils Neutrophils Account for 50-70% of circulating WBCs 12µm diameter 2 – 5 lobed nucleus Granules not stained well by either acidic or basic dyes Granules contain lysosomal enzymes and bactericidal agents Neutrophils First on the site of injury Attack, engulf and digest bacteria marked with antibodies or complement proteins Produce H2O2 and O2- which can kill bacteria While attacking bacteria they release: ▫ Prostaglandins: capillary permeability ▫ Leukotrienes: attract phagocytes & coordinate immune response Neutrophils Life span of approx. 10 hrs. but may be 30 min or less when actively engulfing debris or pathogens Eosinophils Granules stained with eosin (red dye) or acidic dyes 2 – 4% of circulating WBCs Similar in size to neutrophils Bi-lobed nucleus Neutrophil and Eosinophil Eosinophils Engulf antibody-coated bacteria, protozoa or cellular debris Mainly releases cytotoxic substances destroying parasites (flukes, parasitic roundworms) Increase during allergic reactions Attracted to injury sites; release enzymes to reduce inflammation  Basophils Numerous granules stained by basic dyes Granules purple or blue Bi-lobed nucleus (often obscure) 8 – 10 µm diameter Account for less than 1% of circulating WBCs Basophils Migrate to injury sites and intensify inflammation Discharge granules of ▫ Histamine: dilates blood vessels, increase capillary permeability resulting in oedema/swelling ▫ Heparin: prevents clotting ▫ Chemicals that attract eosinophils and other basophils Monocytes Spherical May exceed 15µm diameter Large oval or kidney-bean shaped nucleus 2-8% of circulating WBCs Monocytes Remain in circulation for about 24 hours Enters peripheral tissues and becomes Macrophages ▫ Macrophages are aggressive phagocytes engulfing items as large or larger than themselves ▫ Release chemicals that attract and stimulate neutrophils, monocytes and fibroblasts http://www.itb.cnr.it/flex/images/D.0ce220a1911164afd50b/boraschi_1.jpg Lymphocytes Spherical 7 - 8µm diameter Large, round nucleus Thin cytoplasm surrounds nucleus 20 – 30% of circulating WBCs Continuously move between bloodstream and peripheral tissues Types of Lymphocytes T cells: cell-mediated immunity ▫ Specific defense against foreign cells and tissues B cells: humoral immunity ▫ Attack foreign antigens ▫ Differentiate into Plasma Cells which produce antibodies Types of Lymphocytes Natural killer (NK) cells: immune surveillance ▫ Detect and destroy abnormal tissue cells ▫ Helps prevent cancer Platelets Cytoplasmic fragments of megakaryocytes Flattened discs; appear spindle-shaped in blood smear 4µm average diameter, 1µm thick No nucleus Lifespan of 9 – 12 days then phagocytised in spleen Megakaryocytes. (A) & (B) immature cells. (C) mature cell producing platelets. (Source: Battinelli et al. 2001). Platelet Functions Release chemicals important to the clotting process Formation of a temporary patch in the walls of damaged blood vessels Contraction after clot formation HEMOSTASIS Hemostasis The process of blood halting The arrest of bleeding from a broken blood vessel and The establishment of a framework for tissue repair Phases of Hemostasis Vascular Platelet Coagulation Hemostasis The Vascular Phase When the vessel wall is cut Vascular Spasm - The smooth muscle in the wall of the blood vessel contract Hemostasis The Vascular Phase (cont’d) Endothelial cells of vessel: ▫ Contract and expose basal lamina to blood ▫ Release chemicals and hormones (Adenosine Diphosphate , tissue factor, prostacyclin & endothelins) Plasma membranes of endothelial cells become “sticky” ▫ Endothelial cell membranes on opposing sides of the blood vessel stick together Platelet Phase Platelet Adhesion – platelets stick to endothelium, basal lamina and collagen fibres Platelet Aggregation – platelets accumulate at injury site and stick to each other = Platelet Plug Platelet Phase Platelet Activation ▫ Platelets become spherical and develop cytoplasmic processes ▫ Platelets produce various chemicals  ADP – platelet aggregation and secretion  Thromboxane A2 & Serotonin – vascular spasms  Clotting factors – blood clotting  Platelet-derived growth factors – promotes vessel repair  Calcium ions –platelet aggregation and steps in clotting process Platelet Phase The Coagulation Phase Blood clotting Conversion of fibrinogen to fibrin Fibrin covers platelet plug trapping blood cells > Blood clot Involves a variety of clotting factors in a chain reaction of events ▫ Extrinsic Pathway ▫ Intrinsic Pathway ▫ Common Pathway Coagulation Phase http://www.as.miami.edu/chemistry/2086/Chap19/new-Ch-19-part-2_files/image005.jpg The Extrinsic Pathway ▫ Begins in the blood vessel wall ▫ Damaged endothelial cells or peripheral tissues release Tissue Factor (Factor III) ▫ TF combines with Ca2+ and Factor VII to activate Factor X in the Common Pathway ▫ Short and fast The Intrinsic Pathway ▫ Factor XII in blood becomes activated on exposure to collagen fibres ▫ Platelets release a variety of factors (PF-3 etc) ▫ Ca2+ aids activation of CF IX ▫ Activated CF IX combines with CF VIII which activates Factor X Coagulation Phase – The Common Pathway Factor X is activated and forms the enzyme Prothrombinase Prothrombinase converts Prothrombin to Thrombin Thrombin converts Fibrinogen to Fibrin