1) blood cells 2023.pdf

Blood Cells Dr. Silvia Boyajian Blood It is specialised type of connective tissue Composition: Variety of cells suspended in a fluid medium called plasma Functions of blood Transports nutrients and respiratory gases Transports waste products to organs and tissues where they can be recycled or releas...

Blood Cells Dr. Silvia Boyajian Blood It is specialised type of connective tissue Composition: Variety of cells suspended in a fluid medium called plasma Functions of blood Transports nutrients and respiratory gases Transports waste products to organs and tissues where they can be recycled or released Transports hormones Transports immune cells throughout the body Helps regulate body temperature Maintains of acid-base and osmotic balance Characteristics pH of 7.4 Colour is dependent on amount of oxygen More oxygen= brighter the red Less oxygen= duller the red 5-6 litres of blood in an average adult moves unidirectionally within the closed circulatory system Physical Characteristics Fluid –Living 45%  Cells (formed elements) –RBC Erythrocytes(carry oxygen) –WBC Leukocytes (immune) –Platelets Thrombocytes(clotting) Buffy coat –Non living (Matrix) 55%  Plasma (pale yellow fluid) –90% water –10 % (electrolytes, nutrients, proteins (albumin), waste (CO2, ammonia, urea), gases, hormones) HEMATOCRIT: Ratio of the volume of RBCs to the volume of whole blood Example: a hematocrit value of 40% means that there are 40 ml of RBCs in 100 ml of whole blood Normal hematocrit: Males=40-53% Females= 36-48% Plasma Essentially aqueous solution of inorganic salts which is constantly exchanged with extracellular fluid of body tissue Plasma also contains  Plasma Proteins of 3 main types A- Albumin B- Globulin C- Fibrinogen Plasma proteins collectively exert a colloid osmotic pressure within the circulatory system which helps regulate the exchange of aqueous solutions between plasma and ECF Albumins: constitute the bulk of plasma proteins Bind insoluble metabolites such as fatty acids and serve as transport proteins Globulins: includes the antibodies of immune system transport protein Fibrinogen: soluble protein which polymerises to form the insoluble protein fibrin during blood clotting Blood cell types Three major classes: 1- Red Blood Cells (RBCs) (erythrocytes) 2- White Blood Cells (WBCs) (leukocytes) 3- Platelets (Thrombocytes) All are formed in the bone marrow a process known as Haemopoiesis Erythrocytes: involved in transport of (O2 and CO2) Function exclusively within the vascular system Leukocytes: Important part of defence and immune system Act mainly OUTSIDE blood vessels in the TISSUES Platelets: play a vital role in the control of bleeding (haemostasis)by: 1- Plugging the defects in blood vessels 2- Actvating the blood clotting cascade Methods used to study blood and bone marrow To make a smear on a glass slide  after fixation  stained by a polychromatic stain (Giemsa, Wright, Leishman)  distinctive staining characteristics ( according to the affinity of the various cellular organelles to the different stains employed) A- Basophilia (deep blue): affinity for the basic dye methylene blue characteristic of DNA in nucleus and RNA in the cytoplasm eg. Ribosomes B- Azurophelia (purple): affinity for azur dyes, typical of lysosomes (azurophilic granules in leucocytes) C- Eosinophilia (pink): affinity for acidic dye (eosin) particular feature for hemoglobin within erythrocytes D- Neutrophilia (salmon pink/ lilac): characteristic of the specific cytoplasmic granules of neutrophil leucocytes (the dye is NOT of neutral PH) Erythrocytes Erythrocytes (RBCs) Small, pink biconcave discs 7-8 µm in diameter Transport oxygen and CO2 cytoplasm is full of hemoglobin molecules Have no nuclei or organelles Pick up O2 at lung capillaries and release it at body tissue capillaries Male: 4.5-5.5 million/mm3 Female:4-5 million/mm3 During their maturation process, the erythrocytes extrude their nuclei, and the mature RBCs enter the bloodstream, without their nuclei Size 7-8 µm in diameter (7.5 µm) Thickness 2.6-µm thick at the rim, but only 0.75-µm thick in the centre Erythrocytes can be used as a size reference for other cell types Fate: Survive for ~100-120 days in the circulation. Worn out RBCs are removed by macrophages of the spleen, bone marrow and liver. (without organelles  erythrocytes are unable to replace necessary enzyme and membrane proteins) LM: Blood film stained with Leishman:  Rounded  Non nucleated  Acidophilic (with pale central area) EM: Have no nucleus or organelles Filled with hemoglobin Electron dense and homogenous Eosinophilia/ acidophiliadue to their High content of Hemoglobin (which is a basic protein) The pale staining of the central region is a result of its biconcave disc shape Biconcave shape provides 20-30% greater surface area than a sphere relative to cell volume, thus significantly enhancing gas exchange The biconcave shape along with the fluidity of the plasma membrane (50% proteins) permits erythrocytes to bend and adapt to the small diameters and irregular turns of capillaries (34μM in diameter Normochromic RBCs Erythrocyte consists of an outer plasma membrane enclosing hemoglobin and a limited number of enzymes necessary for maintenance of plasma membrane integrity and gas transport functions Immediately beneath the plasma membrane is a meshwork of proteins(Spectrin and Ankyrin) forming a cytoskeleton responsible for the biconcave shape of erythrocyte This submembranous meshwork: Stabilizes the membrane Maintains the cell shape Provides the cell elasticity required for passage through capillaries The cell membrane is highly selective and flexible Rouleaux appearance occurs to some extent in all films Rouleaux formation: RBCs may adhere to one another loosely in stacks called Rouleaux (pile of coins) In slow (not in normal) circulation Due to surface tension caused by their biconcave surface (reversible) Reticutocytes Are the immature form, in which erythrocytes are released into the circulation from the bone marrow They still contain sufficient : mitochondria ribosomes Golgi To complete cytoskeleton and the remaining 20% of haemoglobin synthesis Final maturation into erythrocytes occurs within 24-48 hours of release The rate of release of reticulocytes into the circulation generally equals the rate of removal of spent erythrocytes by the spleen and liver Reticulocytes constitute slightly less than 1% of circulating red blood cells In routinely stained blood smears: reticulocytes canNOT be easily distinguished from mature erythrocytes. When fresh blood is incubated with basic dye ((brilliant cresyl blue)), a blue-stained reticular precipitate is formed in the reticulocytes due to the interaction of the dye with ribosomal RNA remnants, the technique is called supravital staining Reticulocytosis An increase in the number of reticulocytes is considered an abnormality but the cell itself is not an abnormal erythrocyte Anemia: a decrease in the total number of RBCs (and/or hemoglobin) Polycythemia: an increase in the total number of RBCs People living at high altitudes usually have higher RBC count as a response to lower oxygen levels. Athletes whose demand for oxygen is more elevated, also have higher RBC counts. Abnormalities of Erythrocytes Change from the normal Size Shape Staining properties of erythrocytes are important indicator of disease. However, some of these abnormalities may be found in healthy individuals Abnormal sizes: Microcytes(9 µm) Anisocytosis(different sizes) (abnormal variations of the size) Abnormal staining: Hypochromia: Denotes a decrease in the intensity of staining Indicates a decreased amount of hemoglobin Frequently accompanies microcytosis Hypochromic microcytic anemia Abnormal shapes: Due to changes either in the cell membrane or Hb content Spherocytes Ovalocytes Poikilocytes The cells may show blunt/ pointed projections from their surfaces Sickle cell anemia results from abnormal hemoglobin Sickle cell One of the most sever changes in shape occurs during SICKLING of RBCs in sickle cell anemia where erythrocytes take on the form of crescents Howell-Jolly bodies: nuclear fragments left over from the nucleated precursors of the red cells Leukocytes Leukocytes Originate in the bone marrow and released continuously into the blood Travel in bloodstream but function mainly OUTSIDE blood vessels (in loose CT) Leukocytes form a mobile army that helps protect the body from damage by bacteria, viruses, parasites, toxins and tumor cells 5 types organized into 2 groups depending on nuclear shape and cytoplasmic granules –Granulocytes (single, multi-lobed nucleus) I. Neutrophils II. Eosinophils III. Basophils –Agranulocytes (mononuclear leukocyte) I. Lymphocytes II. Monocytes Leukocytes, or WBCs, are nucleated and subdivided into granulocytes and agranulocytes, depending on the presence or absence of specific granules in their cytoplasm These specific granules stain red with acidic stain such as eosin These specific granules stain with basic stain Granulocytes Cytoplasmic granules (containing enzymes or chemicals) makes cytoplasm look grainy Single multi-lobed nucleus (segmented) All are phagocytic; they engulf and consume foreign cells and material 3 main types: Small granules, pale pink/salmon pink Large granules, Red Large granules, blue Cytoplasmic granules Specific granules Secondary granules Non-specific granules Azurophilic granules Lysosomes Primary granules Neutrophil The most common leukocyte in blood constitute 40-75% of circulating leukocytes Characterised by the shape of the nucleus which contains small lobed connected by thin filaments When mature there are usually 5 lobes connected by fine strands of nuclear material. In less mature neutrophils the nucleus is less lobulated 2-5 lobes in nucleus connected by “threads” of nuclear material (polymorphs) Light pink cytoplasm Called neutrophils because cytoplasm takes up red (acidic) and blue (basic) stains equally 1. 2. 3. Specialized for responding to: bacterial invasions Acute infections acute pyrogenic infections Neutrophils are short-lived cells with a half-life of 6-8 hours in blood and a life span of 1-4 days in connective tissues before dying by apoptosis. Neutrophils are the first WBCs that leave the blood in large numbers to reach the site of inflammation Cells of acute infection 1-The most abundant 2-The most motile 3-Neutrophil chemotactic factors (chemotaxins) are the first released In females, the inactive X chromosome (Barr body) may appear as a drumstick-like appendage on one of the lobes of the nucleus (about 3% of neutrophils in peripheral blood) Granules in neutrophils Specific granules (secondary) (most numerous) Small in size -Lysozyme: act against cell wall -Phagocytin (bactericidal) -Lactoferrin (bacteriostatic) -Collagenase (barely visible by light miscroscopy) Azurophilic granules (primary) (less numerous) Somewhat larger in size -Myeloperoxidase (bacteriocidal) -Acid hydrolase -Defensins Different names for neutrophils: Polymorphs Pus cells Microphages Cells of acute inflammation The ability of neutrophils to survive in an anaerobic environment is highly advantageous, because they can kill bacteria and help clean up debris in poorly oxygenated regions, for example, damaged or necrotic tissue lacking normal microvasculature Neutrophilia: increase in the number of neutrophils in the circulation this does not necessarily imply an increase in neutrophil production Intense muscular activity and administration of epinephrine can produce APPARENT neutroplelia they causes neutrophils in the marginating compartment to move into the circulating compartment Glucocorticoids: increase the mitotic activity of neutrophil precursors in the marrow  increase blood count of neutrophils Neutrophilia that occurs during bacterial infections  increase production of neutrophils for short duration of these cells in bone marrow Neutropenia Eosinophils Accounts for 1-6% of leukocytes in circulating blood Usually have bi-lobed nuclei connected by a short “thread” of nuclear material Large cytoplasmic granules, which stain red with the acidic eosin dye Functions: Eosinophils are phagocytic cells but less bacteriocidal than neutrophils Eosinophils have a particular phagocytic affinity for antigen-antibody complex Help in ending allergic reactions and in fighting parasitic infections All eosinophils have receptors for IgE (important in the destruction of parasites, this is not present on neutrophils During allergic reactions Eosinophils undergo chemotaxis in response to histamine and eosinophil chemotactic factor of anaphylaxis (ECF-A) released from basophils and mast cells Eosinophils ameliorate some aspects of hypersensitivity reactions They neutralise histamine and produce a factor (eosinophil-derived inhibitor) which inhibits mast cell degranulation Eosinophilia: increase number of circulating eosinophils are found in 1- many types of parasitic disease (defense against parasites is one of their principle functions) 2- in some allergic disease such as hay fever and asthma Specific granules (Crystalloid granules): -Oval in shape, with flattened crystalloid cores -Two parts: 1- Externum(pale):contains histaminase and sulfatase 2- Internum(dark):contains basic protein to kill parasites The eosinophils granules are lysosomes and contain the usual lysosomal enzymes, they show a higher content of peroxidase than do the azurophilic granules of neutrophils and lack lysozyme and phagocytin Crystalloid granule Basophils Rarest leukocyte –might not see these under the microscopes (less than 1%) Usually have bi-lobed, S-shaped nuclei obscured by the large basophilic granules Has large granules that stain dark purple/ blue in basic dyes (basophil= basic loving) Granules contain histamine, heparin and eosinophilic chemotactic factor that mediate inflammation in allergic reactions and parasitic infections Mast cell Exposure may be by ingestion, inhalation, injection, or direct contact In some individuals substances such as certain pollen proteins or specific proteins in food are allergenic, that is, elicit production of specific IgE antibodies, which then bind to receptors on mast cells and immigrating basophils. Upon subsequent exposure, the allergen combines with the receptor-bound IgE molecules, triggering rapid exocytosis of the cytoplasmic granules. Release of the inflammatory mediators in this manner can result in bronchial asthma, cutaneous hives, rhinitis, conjunctivitis, or allergic gastroenteritis. Immediate or type 1 hypersensitivity In some individuals a second exposure to a strong allergen, such as that delivered in a bee sting, may produce an intense, adverse systemic response. Basophils and mast cells may rapidly degranulate, producing vasodilation in many organs, a sudden drop in blood pressure, and other effects comprising a potentially lethal condition called Anaphylaxis or anaphylactic shock. Agranulocytes Single non-lobulated nucleus Granules in cytoplasm are too small to see (nonspecific granules, azurophilic granules, primary granules, lysosomes) 2 types based on structure (not cell lineage): –Lymphocytes –Monocytes Monocytes Largest leukocytes Constitute 2-10 % of leukocyte in peripheral blood Bluish cytoplasm (frosted glass appearance)& a large Cshaped nucleus Highly motile and phagocytic Travel through bloodstream to reach connective tissues, where they transform into macrophages (large phagocytic cells) Chronic infections Are precursor cells of macrophages, osteoclasts, microglia, and other cells of the mononuclear phagocyte system in connective tissue All monocyte-derived cells are antigen-presenting cells MONONUCLEAR PHAGOCYTIC SYSTEM ( all characterized by phagocytic activity) osteoclasts Bone Kupffer Cells liver Microglia CNS Dust cells lung Dendritic cells Lymph node spleen macrophages Bone marrow Connective tissue Langerhans cells epidermis Lymphocytes Smallest leukocytes (slightly larger than erythrocytes) The second most common leukocyte in circulating blood and make up 20-25% of differential white cell count Round nucleus occupies most of cell volume Cytoplasm is light clear blue Increased numbers are commonly seen in viral infections Lymphopoiesis: the process by which lymphocytes are formed Precursor cells in bone marrow Thymus T Lymphocytes Bone Marrow B Lymphocytes Directly into blood Natural killer lymphocytes The amount of cytoplasm depends upon state of activity of the lymphocyte, in circulating blood there is: 1- Predominance of small inactive lymphocytes (6-9 μm in diameter) 2- Large lymphocytes (9-15 μ m) make up about 3% of lymphocytes in peripheral blood represent activated lymphocytes en route to the tissues where they will become antibody-secreting plasma cells, they also include natural killer cells In the large lymphocyte  the cytoplasm is readily visible but in the small lymphocyte the cytoplasm is almost too sparse to be seen (contain few mitochondria, rudimentary golgi apparatus, minimal endoplasmic reticulum but large number of ribosomes account for basophilia (blue cytoplasm) Lymphocytes vary in life span according to their specific function, some live for a few days and some live for many years Cell mediated immunity T cells –Has different types, some directly kill foreign or infected cells; others activate phagocytes to destroy microbes Humoral immunity B cells –Differentiate into plasma cells –Secrete antibodies that bind to specific antigens and mark them for destruction by phagocytic cells Long term immunity Neutrophils and monocytes are highly phagocytic and engulf microorganisms and cell debris in a NON-SPECIFIC manner (Innate immunity) While the activity of lymphocytes is always directed against SPECIFIC foreign agents (Adaptive immunity) The small lymphocyte has scanty cytoplasm (contain few organelles but large number of ribosomes ) Account for basophilic Innate immunity: We are born with innate immunity. It is non-specific, which means that the innate cells are not able to distinguish one type of pathogen from another. Adaptive (acquired) immunity: is the body's ability to recognize and respond to specific foreign substances (antigens: microbes, parts of microbes, or non-microbial substances, such as pollen) Cells of innate immunity: Neutrophils, Basophils, Eosinophils, Mast cells, Monocytes (macrophages and dentritic cells), natural killer cells Cells of adaptive immunity: B and T lymphocytes Cytotoxic Kill virus-infected, transplanted and neoplastic cells (adaptive immunity) Helper Help cytotoxic T cells and B cells in their immune function Suppressor Suppresses immune response to self Ag Suppresses immune response of T and B lymphocytes Suppressor T cells switch off the immune response when the stimulus is removed Damage to suppressor cells can result in autoimmune disease Memory cells allow a more rapid response if the antigen appears again later which allows a very rapid response upon subsequent exposure to the same antigen. Basis of immunity/vaccination Natural killer cells and T cells play a major role in graft rejection Never Let Monkeys Eat Bananas Most common to least Thrombocytes (Platelets) Small non-nucleated cytoplasmic fragments Formed by fragmentation of the cytoplasm of megakaryocytes in the bone marrow Number: 200,000-400,000/mm3 Shape: biconvex discs Cytoplasm: purple, granular Diameter: 2-4 um Lifespan about 10 days Control the bleeding by plugging the defects in blood vessels and activating blood clotting cascades In stained blood smears, platelets often appear in clumps Platelete has 2 zones 1- Outer pale basophilic (clear) perpheriral zone: hyalomere 2- Central dark granular zone: granulomere In stained blood smears, platelets often appear in clumps Hyalomere: contains cytoskeleton and membranous channels Cytoskeletal elements Microtubule Actin filaments Membrane channels Open canalicular system Dense tubular system Maintain shape and help contractions of platelets and squeezing Granulomere: contains granules and organelles Alpha granules: clotting factors, growth factors Dense (delta) granules: serotonin (absorbed from plasma), ATP, ADP Lambda granules: lysosomes (aid in clot resorption) Their main function is to continually monitor the vascular system and detect any damage to the endothelial lining of the vessels. If the endothelial lining breaks, the platelets adhere to the damaged site and initiate a highly complex chemical process that produces a blood clot Thus preventing blood loss Thank you