Lect. 10 blood cells

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  • hemoglobin S polymerizes at low O 2 tensions; and this causes the red cells to become sickle-shaped, hemolyze, and form aggregates that block blood vessels. The result is the severe hemolytic anemia known as sickle cell anemia.
  • Lect. 10 blood cells

    1. 1.  Vehicle for transportation of gases, nutrients, metabolic waste products & hormones in the body  Consists of cells and molecules essential in transport processes – laboratory analysis of blood  Disease Dx.  Plasma – fluid medium: 90% H2O, 8% CHON, 1% inorg. salts, 0.5% lipids, 0.1% CHOs.  Salts – constantly exchanged with ECF of body tissues
    2. 2.  Contain 3 grps. of proteins (not seen in light or electron Mx.)  Blood coagulation proteins  Albumin  Globulins (alpha, beta, gamma)  Alpha – proteases, antiproteases, transport CHONS  Beta – transferrin, other transport CHONS  Gamma – immunoglobulins (GAMDE)  Plasma proteins are synthesized from liver except immunoglobulins that are synthesized from plasma cells.  The plasma proteins exert colloidal osmotic pressure within circulatory system that regulate the exchange of fluid between extracellular space and plasma.
    3. 3.  Erythrocytes (red blood cells)  Leucocytes (white blood cells)  Agranular WBC/Agranulocytes (lymphocyte, monocyte)  Granular WBC/Granulocytes (neutrophil, eosinophil, basophil)  Thrombocytes (platelets) – fragments of megakaryocytes in BM (bone marrow)  All are formed from myeloid tissue (BM) – hemopoiesis (hematopoiesis)
    4. 4. Number and Percentage of Blood Corpuscles (Blood Count). Corpuscle Type Approximate Number per La   Approximate Percentage Erythrocyte  Female: 3.9–5.5 x 106 /L     Male: 4.1–6 x 106 /L   Reticulocyte    1% of the erythrocyte count Leukocyte  6000–10,000   Neutrophil 5000 60–70% Eosinophil 150 2–4% Basophil 30 0.5% Lymphocyte 2400 28% Monocyte 350 5% Platelets 300,000
    5. 5.  After fixation: Blood smears are subjected to polychromatic ROMANOWSKY STAINING METHOD (Wright, Giemsa, Leishman)  Basophilia (deep blue) – methylene blue  Azurophilia (purple) – azure dyes  Eosinophilia / Acidophilia (pink) – eosin dyes  Neutrophilia (salmon pink/lilac) – erroneously believed that neutral pH of the affinity of cells – as seen in neutrophil WBCs.
    6. 6.  (+) Hemoglobin (Hb) – O2-carrying pigments consist of heme and ferrous molecules  Transport of O2 and CO2  Exclusively functions within blood vascular system  ERYTHRON – mass of RBC + precursors in BM  Normal BC: M=4.1-6M; F=3.9-5.5M cells  Increased RBC – Polycythemia  Decreased RBC - Anemia
    7. 7. Each heme portion can bind 4 molecules of oxygen How many oxygen molecules can 1 Hb molecule carry? α β 4 Fe ion – containing - heme and 4 polypeptide chains - globin
    8. 8.  Each RBC has approx. 280 milllion hemoglobin molecules  Hb can also bind CO2 and CO  CO2 and O2 have distinct carry sites  CO and O2 have the same site  CO has a greater affinity for heme thus excluding O2  CO is such a dangerous gas when inhaled.
    9. 9. Before release:  All cytoplasmic organelles degenerate and extrudes their nucleus Fully mature:  Consist of outer plasma membrane enclosing Hb and limited enzymes to maintain the cell. (deform readily and pass through capillaries)
    10. 10.  In peripheral blood: Immature RBC with retained residual nuclear material. They are freshly released from bone marrow.  Final maturation into RBC: within 24-48h of release  Their presence equals the rate of removal of spent RBCs by the spleen and liver.  Supravital staining – diagnostic detection of reticulocytes  Reticulocytosis – high reticulocytes in circulating blood since the rate of hemopoiesis is increased in hemorrhage and hemolysis.
    11. 11.  Biconcave-shaped discs cells with pale- staining central area  Ave. cell size: 7.2µm; in capillaries: 3-4µm  Spectrin – skeletal protein that maintains RBC shape  Average life span: 120 days in circulation (old spheroidal RBCs are brought to spleen and liver recycles heme to Hgb).
    12. 12.  RBC Size: Diameters greater than 9µm are called macrocytes, and those with diameters less than 6µm are called microcytes.  The presence of a high percentage of erythrocytes with great variations in size is called anisocytosis (Gr. aniso, uneven, + kytos). Sickle cell Anemia – gene mutation in beta chain ofHgb
    13. 13.  Defense and immune systems of the body  Mainly acts outside the blood vascular system in tissues  WBC seen in peripheral blood smear – are merely in transit between various sites of activity  GRANULOCYTES  AGRANULOCYTES / MONONUCLEAR LEUCOCYTES  DIAPEDESIS – ability of the WBC to migrate in sites of infection and in normal activities across blood vessel thus, are called WANDERING CELLS.
    14. 14.  Contains specific granules in their cytoplasm and multi-lobed nucleus (polymorphonuclear leucocyte)  Neutrophils  Eosinophils  Basophils
    15. 15.  Commonly referred to as polymorphs sinceCommonly referred to as polymorphs since they are the most numerous in normalthey are the most numerous in normal circulation.circulation.  Count: 40-75% of circulating leucocytesCount: 40-75% of circulating leucocytes
    16. 16.  Salient features: Highly lobulated (polymorphic nucleus~5 lobes connected by nuclear material) Females (XX) – (+) drumstick chromosome (X chromosome or Barr body) Cytoplasm – lightly stippled with lilac granules, cytoplasm is light pink (azurophilia) Granules – Microbicidals: myeloperoxidase & neutrophil defensins
    17. 17. Dead neutrophils, bacteria, semidigested material, and tissue fluid form a viscous, usually yellow collection of fluid called pus.
    18. 18.  Short-lived PMN leukocyte in the circulation  Highly responsive in disease state  Role: phagocytosis (acute inflammatory response)  Recruited to the site of infection via “chemotactic molecules” (chemical attractant)  Also express similar receptors on its surface as the macrophage.
    19. 19.  Bilobed nucleus; eosinophilic granules in cytoplasm; (1-6% of total WBC)  Small percentage is found in circulation  Most are found in tissues at the same site as mast cells.  Plasma membrane – have different immunoglobulin (Ig) & complement receptors from other WBC  (+) IgE receptors; while neutrophils (-) IgE receptors
    20. 20.  Induce and maintain inflammatory responses due to allergy or anaphylactic hypersensitivity  (Ex: allergic rhinitis (hay fever) & asthma) – CHEMOTAXIS – migration of eosinophils to tissues  Main host defense mechanism against parasitic infection (helminths).  They act as pro-inflammatory leucocytes, mediated by release of their granules (degranulation) and leukotrienes.
    21. 21.  Via intermediary molecule, IgE antibody that has bound to the helminth  Eosinophil has FcεR on its surface that binds with the Fc region of the IgE
    22. 22. Release of:  Major basic proteins  Eosinophil cationic proteins * Both are toxic to the helminth Helminths are resistant to lysosomal enzymes and reactive oxygen intermediates generated in the phagocytes.
    23. 23.  Bilobed nucleus obscured by large, densely basophilic granules with (+) histamine  The granules are highly soluble in water and tends to be dissolved away during common blood smear preparation.  The granules bind with the dye toluidine blue and changes the dye color to red – metachromasia
    24. 24.  Performs degranulation during allergic reactions from environmental antigens (allergens).  release histamine – immediate anaphylactic hypersensitivity
    25. 25.  Basophils – in circulation.  Mast cells – in tissues  Both have similar biological roles  When activated, these cells degranulate and release substances in their surrounding area.  HISTAMINE – makes small blood vessels leaky so that the immune cells can enter the infected tissue.
    26. 26.  Both have FcεR on their surfaces  Fc region of IgE antibodies bind to FcεR of mast cells and basophils.  Degranulation of the cells occurs  Release of histamine and other inflammatory mediators.
    27. 27.  Excessive release of histamine and inflammatory mediators  lead to hypersensitivity reaction  Exaggerated hypersensitivity reaction is called “anaphylaxis” and can lead to death.  Less exaggerated hypersensitivity reaction cause allergies and/ or asthma.
    28. 28.  Non-lobulated nuclei, contain also non- specific cytoplasmic granules but not distinctly stained.  Like the granulocytes, they also carry surface proteins, which are capable of binding to complementary receptors on endothelial blood vessels.  Such binding allows the cells to penetrate into tissues by amoeboid movement (diapedesis).
    29. 29.  Smallest cell among WBC; it is slightly larger than RBC  Round, densely-stained nucleus and small pale, non-granular cytoplasm  20-50% of total WBC; play the central role in all immunological defense mech.  They constantly recirculate lymphoid cells through tissues and back to the circulation as part of immune surveillance.  Large lymphocytes represent activated B / T- forms
    30. 30.  Largest WBC; motile phagocytic cells; precursor of macrophages found in peripheral tissues & organs  Constitute 2-10% WBC; in blood, they circulate for 3-4 days  Precursor of macrophages (migrated monocytes in peripheral tissues); they die in tissues by apoptosis; acute infections, they secrete TNF-α (tumor necrosis factor) a mediator of SEPTIC SHOCK  Large, eccentric, single horseshoe-shaped nucleus (indented nucleus); may contain few granules in its cytoplasm
    31. 31. Table 1. Macrophage Nomenclature in Different Tissues Tissue Nomenclature Blood Circulating macrophage Bone Osteoclasts Central Nervous system Microglial cell Kidney Mesanglial cell Liver Kupffer cell Lung Alveolar Macrophage Lymph Node Lymph Node Macrophage Spleen Splenic Macrophage
    32. 32.  Neutrophils – do not enter the tissues in huge numbers unless they respond to disease stimulus during acute inflammation.  Eosinophils, basophils, monocytes – constantly enters tissues but in relatively low numbers.  Lymphocytes – constantly enter tissues from blood in normal number and exits the tissues via lymphatic system, to reach the lymphoid system.
    33. 33.  Neutrophils and Monocytes – phagocytic and engulf microorganisms, cell debris and foreign particulates in non-specific manner. Their activity can be enhanced and directed by immune responses to specific foreign agents.  Lymphocytes – play the key role in all immune responses and directed against specific foreign agents.
    34. 34. 1. Recognition and Ingestion of the antigen 2. Actual degradation of the antigen in the phagocytic vacuole
    35. 35.  When macrophage extends finger-like projections that surround the antigen.  The antigen becomes contained within a vacuole called a phagosome.
    36. 36. PHAGOCYTE In blood circulation, the macrophage clears away all the wastes and impurities.
    37. 37. Mediated by 1. Lysosomal Enzymes  Lactoferrin – binds iron (depleting an essential nutrient for some microbes).  Lysozyme – destroys some components of bacterial cell walls  Defensins –permeabilizes some bacterial and fungal cells
    38. 38. Mediated by 2.Reactive Oxygen Intermediates: * Due to activation of an enzymatic complex, NADPH oxidase  Superoxide Anion  Hydroxide Peroxidase  Hydroxyl radicals * All are cytotoxic to the microorganism.
    39. 39.  Cells capable of endocytosing antigens, degrading them, and displaying the antigen fragments on their surface in association with MHC proteins. Dendritic cells Macrophages B cells
    40. 40.  Functions in HEMOSTASIS - Control of bleeding  Control of bleeding: plugging defects in blood vessels walls (endothelium) and contributes to activation of blood-clotting cascade mechanism  THROMBUS - clot
    41. 41.  Neutrophilia – elevated neutrophil count; indicates an acute inflammation (common in bacterial infxns.)  Eosinophilia – elevated eosinophil count; allergic rxns. and parasitic infxns.  Lymphocytosis – elevated lymphocytes; usually in viral infxns. (viremia-virus in blood)  Leukemias – elevated leucocyte count corresponding to malignant cells (malignant tumor cells from the bone marrow circulates in the peripheral circulation)
    42. 42.  Neutropenia  Lymphocytopenia  Thrombocytopenia – reduced platelets

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