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183 Cards in this Set
- Front
- Back
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What blood cells do hematopoiesis form? |
erythropoiesis, leukopoiesis, thrombopoiesis. |
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Describe hematopoiesis |
•Production and destruction of blood –an ongoing process –relatively constant number of cell types maintained in circulation. |
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How long do RBCs and Platelets stay in circulation? |
•RBCs and Platelets: entire life spent in circulation. |
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Where do leukocytes live and function? |
•Leukocytes: leave blood; live and function in tissues. |
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What are the three phases of hematopoiesis? |
•1st / yolk-sac phase •2nd / hepatic phase •3rd / bone marrow phase |
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In fetus, red & white cells are formed in several organs before ________ is formed |
•In fetus, red & white cells formed in several organs before bone marrow is formed |
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Describe 1st / yolk-sac phase |
–Begins 3rd week of gestation. –Blood islands form in the mesoderm of the yolk sac. |
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Describe 2nd / hepatic phase |
•Hemopoietic centers appear in the liver. –During the 2nd trimester the liver is the major blood forming organ in the fetus. –Declines during the fifth month •Spleen produces mainly erythrocytes and small no. of granulocytes and platelets. |
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•3rd / bone marrow phase |
•Bone marrow (and other lymphoid tissue involved). •Begins during 2nd trimester of pregnancy. •After birth hematopoiesis takes place in red bone marrow and lymphoid tissues. |
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Red Bone Marrow consists of what? |
- stroma, - hemopoieticcords - sinusoidal capillaries |
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Pluripotent stem cells |
•Pluripotentstem cells arise from daughter cells of totipotent stem cell that become committed to either the myeloid or the lymphoid pathway. |
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Two types of Pluripotent stem cells and what do they give rise to? |
–Lymphoid stem cells (CLP,CFU-Lys) give rise to lymphocytes. –Myeloid stem cells (CMP, CFU-GEMMegs) give rise to all the other blood cell lines. |
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Unipotent and multipotent stem cells |
•Unipotent and multipotentstem cells arising from myeloidstem cells are committed to one of three lineages |
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What are the three unipotent and multipotent stem cells? |
–Erythrocyteline (CFU-E) –Megakaryocyte-plateletline (CFU-Meg) –Granulocyte-monocyteline (CFU-GM) |
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Granulocyte-monocyte line give rise to what? |
CFU-GMs subsequently give rise to CFU-Gs, which are committed to the granulocyte line and CFU-Ms, which are committed to the monocyte line. |
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Common Lymphoid Progenitor (CLP, CFU - L) differentiate to what cells? |
Differentiateinto pre-T, pre-B and pre-NK cells. |
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Lymphopoiesis Stages of Lymphoid stem cells |
1. Lymphoblast 2. Prolymphocyte 3. Lymphocytes |
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CommonMyeloid Progenitor (CMP) |
1.Erythrocyteline (CFU-E) 2.Megakaryocyte-plateletline (CFU-Meg) 3.Granulocyte-monocyteline (CFU-GM) |
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Stages of Erythropoiesis |
•Pro erythroblast •Basophilicerythroblast •Polychromatophilicerythroblast •Orthochromatophilicerythroblast (normoblast) •Reticulocyte (Polychromatophilicerythrocyte) •MatureRBC (erythrocyte) |
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Which stage in Erythropoiesis is not capableof mitosis and the end of this stagenucleus is extruded? |
Orthochromatophilic erythroblast (normoblast) |
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Mitosis in erythropoiesis occurs in what cells? |
•Mitosesoccur in –pro erythroblasts –basophilicerythroblasts –polychromatophilic erythroblasts
(At each of the above stages the erythroblast divides several times.) |
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How long does it require for the progeny of a basophilic erythroblast to reach bloodstream? And why aren't the RBCs not stored in the bone marrow? |
•Approx 1 week is required for the progeny of a basophilic erythroblast to reach bloodstream. •RBCs (nearly all) are released into circulation soon after being formed. •RBCs are therefore not stored in the bone marrow. |
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Orthochromatophilic erythroblast (normoblast) |
–Smallcompact densely stained nucleus. –Cytoplasmis acidophilic dueto large amount of hemoglobin. –Slightlylarger than mature RBC. –Cannotdivide at this stage. –Orthochromatophilicerythroblast extrudes its nucleus and now called reticulocyte. |
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Why is the normoblast cytoplasm acidophilic? |
Cytoplasm is acidophilic due to large amount of hemoglobin |
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Reticulocyte |
- (diffusely basophilic erythrocyte / final stage of erythropoiesis) within thebone marrow - represents an immature, anucleatedRBC. –Afterentering the bloodstream, reticulocyteslose their remaining ribosomesand mitochondria, becoming mature RBCs. - 1%to 3% of circulating RBCs. –Excessiveloss of mature RBCs causes the release of more reticulocytes and theirpercentage in the blood increases. |
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Development of Thrombocytes (Thrombopoiesis) |
MEP (megakaryocytic/ erythrocyte progenitor)-> Megakaryocytecommitted progenitor (MKP) cell-> Megakaryoblast-> Megakaryocyte (Successiveendomitosesunder stimulation by thrombopoietinresults in a megakaryocyte)-> platelets. |
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Megakaryoblast |
•Largecell with a polypoidnucleus. •Divideendomitotically(no daughter cells) - Become Megakaryocyte |
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Megakaryocyte |
Extremelylarge cells, lobulatednucleus, many mitochondria with Golgi bodies. |
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How do megakaryocytic form platelets? |
- Toform platelets, megakaryocytes extend several longbranching processescalled pro platelets. - These cellular extensions penetrate the sinusoidal endothelium shedding fragments of platelets into the circulation. |
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Development Granulocytes (Granulopoiesis) |
•Myeloblast - thefirst histologically recognizable granulocyte precursor •Promyelocyte •Myelocyte •Metamyelocyte •BandCell •MatureLeucocytes |
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Myeloblast |
- large nucleus with large nucleus to cytoplasm ratio, deeplybasophilic cytoplasm. |
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Promyelocyte |
- is characterized by a large nucleus, basophiliccytoplasm and blue/black primary or azurophilic granules containing lysosomal enzymes andmyeloperoxidase |
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Myelocyte |
- exhibits specific granules forcell types. |
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Metamyelocyte |
–Kidney/ bean shaped nuclei Specific granules are more obvious |
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Band cell (Stab cell): |
–Horseshoe-likenucleus –Specificgranulesin the cytoplasm |
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Which cell in Granulopoiesis is recognized as the most immature? |
The myeloblast is the most immature recognizablecell in the myeloid series. It has a finely dispersed chromatin, and nucleoli can be seen. |
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Which cell in Granulopoiesis helps resulting in lineages for the three types of granulocytes and how? |
•Different promyelocytes activate differentsets of genes, resulting in lineages for the three types of granulocytes |
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In which cell does the first visible sign of differentiation appears in Granulopoiesis? |
•The first visible sign of differentiation appears in the myelocytes where specific granules gradually increase in quantity and eventually occupy most of the cytoplasm. |
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When does the nucleus become increasingly segmented in Granulopoiesis? |
•From the myelocyte stage through the metamyelocyte stage to the mature granulocyte forms, the nucleus becomes increasingly segmented. |
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No cytoplasmic granules (Granulopoiesis) |
Myeloblast |
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First (blue) azurophilic granules being secreted in Golgi apparatus (Granulopoiesis) |
Promyelocyte |
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Moderate number of (blue) azurophilic granules and initial production of (pink) specific granules in Golgi zone |
Myelocyte |
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Abundant (pink) specific granules and dispersed (blue) azurophilic granules; Golgi apparatus reduced. |
Metamyelocyte |
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Kineticsof Granulopoiesis |
•Takes2 weeks in the bone marrow –1week for mitotic /proliferative phase –1week for post mitotic /differentiation phase (from metamyelocyte tomature granulocyte) • ½of the PMNs leave the peripheral blood in 6-8 hours. Large reserve pool of PMNspresent in bone marrow. |
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What indicates a bacterial infection in the blood? |
•The appearance of large numbers of immature neutrophils (band cells) in the blood is called a shift to the left and is clinically significant, usually indicating bacterial infection. |
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Stages of MonocytopoiesisCFU-M → monocyte |
•A monoblast,the first differentiating precursor, gives rise to a promonocyte, which matures into a monocyte.• •Monocyte remains in circulation for 16 hours before emigrating and differentiating to atissue macrophage. (interleukins, CSFs and transcription factors control this proliferation and differentiation process) |
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Three components of Redbone marrow |
1.Stroma/reticular connective tissue
2.Hempoieticcords and 3.Sinusoidalcapillaries |
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How do mature blood cells produced in the parenchyma of the cords gain access to circulation? |
•Matureblood cells produced in the parenchyma of the cords gain access to thecirculation by passing through sinusoid walls.
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Bone Marrow Examination
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Diagnosis of leukemiasand other bone marrow disturbances involves bone marrow aspiration. A needle isintroduced through the compact bone, typically at the iliac crest, and a sampleof marrow is withdrawn.
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Types of needles used in Bone Marrow Examination
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- BM biopsy needle
- BM aspiration needle |
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Primary and Secondary site used for
Bone Marrow Examination |
Primary site: iliac crest
Secondary site: sternum |
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Two composition of Blood |
Bloodis a specialized C.T. ofmesodermalorigin composedof: 1. Extracellularmatrix (ECM) called blood plasma: (55%)
- non-cellular portion of the blood 2. Formedelements (blood cells): (45%) –Redblood cells (erythrocytes) –Platelets(thrombocytes) –Whiteblood cells (leukocytes) |
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What are the formed elements/ blood cells composed of?
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–Red blood cells (erythrocytes)
–Platelets (thrombocytes) –White blood cells (leukocytes) |
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Describe Plasma
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•Morethan 90%ofit by weight is water.
•Servesas solvent for solutes. •Soluteshelp maintain homeostasis. •Comprisedof –water: 91-92 % –protein(albumins,globulins, fibrinogen) –othersolutes (electrolytes, nutrients, blood gases, regulatory substances) |
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Serum
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•Aftervenipuncture, blood clots if no anticoagulant has been added to it.
•Thefluidpartabovethe clot is then known as serum. •Serumcantherefore be regarded as plasma without the clotting factors. |
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How is Hematocritor Packed cell volume
determined? |
•Isdetermined by the centrifugingheparinisedblood(blood mixed with anticoagulant) in a standard calibrated tube of a smalldiameter.
•Aftercentrifugation the column of the RBCs and plasma can be measured.
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What are the three layers seen in Hematocritor Packed cell volume?
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•Three layers are seen:
–Supernatant plasma –Buffy coat – leukocytes and platelets –RBC |
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What is the Hematocrit or Packed cell volume? What is the normal values for females and males?
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•Thehematocrit is an estimate of the volumeof packed erythrocytes per unit volume of blood.
•Thenormal value is 40–50% in men and 35–45% in females.– |
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What does it mean when the Hematocrit or Packed cell volume increases? decreases?
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•↑ in persons living at high altitudes, in dehydrated state, polycythemia etc.
•↓ in anemia, leukemia, bone marrow failure. |
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Components of Plasma protein |
•Albumin
•Globulins: Alpha, Beta and Gamma •Complementproteins •Fibrinogen. |
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Albumin
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most abundant plasma protein and plays an important role in maintaining a high colloid osmotic pressure that keeps fluid within the blood vessels. |
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Low levels of Albumin results in?
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Low levels of albumin result in a net loss of fluid from the intravascular space into the extracellular tissue compartment, resulting in edema.
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Describe three types of globulins
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Alpha and Beta globulins: synthesized by liver and other cells, include transferrin and other transport factors; fibronectin; prothrombin and other coagulation factors entering blood from tissues.
Gamma-globulins: these are immunoglobulins, or antibodies, synthesized by plasma cells. |
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Complement proteins
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a system of factors important in inflammation and destruction of microorganisms. •
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Fibrinogen
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is a plasma protein component of the coagulation cascade that converts to insoluble fibrin, forming a blood clot
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Peripheralblood smear are usually stained with which dye? Whats that dye mixture? |
Bloodsmears are routinely stained with
Romanowsky type dye (eg, Giemsa,Wright's, Leishman's) amixtures of Eosin (acidic) and Methyleneblue (basic) dyes. |
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Steps of Peripheralblood smear
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1. Prick finger and collect small amount of blood.
2. place a drop of blood on slide. 3. Leave a thin layer of blood on the slide by using a second slide to pull the drop of blood across the slide surface. After blood dries, apply a stain for contrast and place a coverslip on top. 4. When viewed under microscope, blood smear reveals components of formed elements. |
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What will a normalstained blood smear contain? |
-Lymphocytes
-Erythrocytes -Neutrophils -Monocytes -Platelet |
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Formed Elements (blood cells)
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•Bloodcells are produced and replaced in blood-forming organs (mostly bone marrow, inthe adult), donot develop or replicate in the circulation,and have a limited lifespan.
•RBCsand platelets function within the blood vasculature. •With the exception of the basophil,WBCs exit the vessels and exert their effects within body tissues. |
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"Complete Blood Count (CBC)"
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•The normal proportion of each type of blood cell lies within narrow limits, as determined by a “Complete Blood Count (CBC)”
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"Differential leukocyte count"
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“Differential leukocyte count" values will help to identify specific white cell types
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Average of COMPLETE BLOOD COUNT (CBC)
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•RBC:
–Male: 4.5 - 5.9 million /mm3 of blood –Female: 3.5 - 5.5 million /mm3of blood •WBC: 3600 - 11,200 /mm3 of blood (100%) •Platelet count: 140,000 - 440,000 /mm3 |
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Order of WBC from highest to lowest count
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•WBC: 3600 - 11,200 /mm3 of blood (100%)
–Neutrophils: 45 - 79 % –Lymphocytes: 16 - 47 % –Monocytes: 0 - 9 % –Eosinophils: 0 - 6 % –Bands: 0 - 5 % –Basophils: 0 - 3 % • |
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What do erythrocytes in their mature form lack and how do they survive? |
•Erythrocytesin their mature form lack most internal organelles and survive by anaerobic glycolysis.They do not undergo apoptosis.• |
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How are Erythrocytes shaped? and what is its benefit? |
- Erythrocytes are biconcave disks of 7.5 µm in diameter with central pallor. - The biconcave shape provides erythrocytes with a large surface-to-volume ratio, thus facilitating gas exchange. |
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How do Erythrocytes develop in the bone marrow? |
•Develop in the bone marrow as nucleated cells, extruding their nucleus as they leave the marrow to enter the blood. |
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Life span of Erythrocytes |
120 days |
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Which organs remove abnormal RBCs? |
AbnormalRBCs are removed from the circulation largely by the spleen and to a lesserextent by the liver. |
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Erythrocyteswith diameters greater than 9 |
Macrocytes |
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Erythrocytes with diameters less than 6 µm. |
Microcytes |
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Reticulocytes |
Reticulocytesare immature red blood cells that still retain ribosomal RNA, few mitochondria& Golgi complex. |
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What is the stain used for Reticulocytes? |
•Stained with supravital dye cresyl blue, residual ribosomes shows blue precipitates in the cytoplasm. |
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What is the percentage of Reticulocytes in the circulating blood cells and what is their rate of release? |
•1% -3 % of circulating red blood cells. •The rate of release of reticulocytes from the bone marrow is proportional to the rate of removal of RBCs from the peripheral blood. |
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When do the number of Reticulocytes increase? |
Increase no. of reticulocytes in the blood is seen in: –hemorrhage –exposure to high altitudes - bone marrow pathology |
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What are the Erythrocytemembrane proteins ? |
•IntegralMembrane Proteins •PeripheralMembraneProteins |
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Integral Membrane Proteins |
–are in the lipid bilayer –express specific blood group antigens –Glycophorin C and Band 3 proteins |
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Peripheral Membrane Proteins |
–Organized as lattice network on the inner surface of the cell membrane. –Spectrin, actin, band 4.1 protein, adducin, band 4.9 protein and tropomyosin. –lattice is bound to the lipid bilayer by the protein Ankyrin. |
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Hereditaryspherocytosis |
•Mutation in spectrindestabilizingthe spectrin-actincomplex of the cytoskeleton. Such RBC adopt a spherical shape and are osmoticallyfragile. • |
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How does Hereditary spherocytosis look in a blood smear? |
•In a blood smear, the affected cells lack the pale area in the center because they are spherical. |
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Affected Hereditary spherocytosis blood cells are prone to what? |
•These fragile cells are prone to rupture, leading to anemia |
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What is the principal site for the removal of worn-out rbcs? (Hereditary spherocytosis) |
Spleen is the principal site for the removal of worn-out rbcs, individuals with spherocytosis show splenomegaly. |
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What are the clinical symptoms of Hereditary spherocytosis? |
The clinical symptoms are a triadof mild anemia, intermittent jaundice, and splenomegaly. |
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Hereditaryelliptocytosis |
- Deciencyin band 4.1 proteins resultsin elliptical erythrocytes. - Theircytoskeletaldefects prevent them from reverting to normal biconcave disk form, and theyremain stuck in the elliptical shape, which results in premature destruction ofthe cells, or hemolysis. |
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Anisocytosis (Hereditaryelliptocytosis) |
Variationin size of RBC |
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Poikilocytosis (Hereditaryelliptocytosis) |
Variationin shape of RBC |
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What is Reuleaux formation? And what causes it? |
•Stacksof RBCs are referred to as ROULEAUX•Increasedlevelsof plasma immnoglobulin may cause rouleaux formation. |
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Hemoglobin(Hb) |
•Proteinfor oxygen &carbondioxide transportand is responsible forstaining with eosin, and cytoplasmic granularity. |
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Types of Hb: |
Types of Hb: –HbA: 96 % of total Hb in adults (2α, 2β) –HbA2: 1.5 - 3% of total Hb in adults (2α, 2δ) –HbF: < 1% of total Hb in adults (2α, 2γ) |
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Structure of Hb |
•Each molecule consists of 4 polypeptide chains of global. Each chain joined to an iron - containing heme group. |
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White Blood Cells |
•Fivetypes of leukocytes are normally present in the circulation. •Theseare divided into two main groups based on their nuclear shape andspecificcytoplasmicgranules. •Withinthe C.T. they act in cellular and humoralimmune responses to foreign agents. |
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WBCs are classified into which two groups? And what classifies them into these groups? |
•On the basis of the presence and type of granule in their cytoplasm and the shape of the nucleus, white blood cells are classified into two groups: –Granulocytes –Agranulocytes |
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Granulocytes (WBC) |
–Multilobulatednuclei and contain primary and secondary (specific)granules. |
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Examples of Granulocytes (WBC) |
•Neutrophils (polymorphs) •Eosinophils •Basophils |
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Agranulocytes |
(Mononuclearleucocytes) –Non-lobulatednuclei and contain primary or azurophilgranules. –Agranulocytes do not have specific granules |
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Examples of Agranulocytes (WBCs) |
•Lymphocytes •Monocytes |
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Leukocytes count |
•Ingeneral, leukocytes number between 3600 - 11,200 /mm3 inblood. •Inan acute infection (e.g. appendicitis), the cell number may rise to 20,000 or40,000/mm3. |
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Order of differential leukocyte count) |
The relative proportion of leukocytes in the blood is usually constant within an individual: –Neutrophils (50%-70%) of total leukocytes –Lymphocytes (20%-30%) –Monocytes (3%-8%) –Eosinophils (2%-4%) –Basophils (0-1%) |
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Neutrophils |
•50–70%,12–15 mm in diameter, with a nucleus consisting of 2–5(usually 3) lobes linked by fine threads of chromatin.• |
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Females may have _____ attached to the nuclear lobe (Neutrophils) |
•Females may have a BARR BODY attached to a nuclear lobe –morphologic expression of the inactivated X - chromosome –found in 3% of female neutrophils (not commonly used for sex determination) |
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Neutrophils with more than 5 lobes are called? Examples? |
•Neutrophils with more than 5 lobes are called hypersegmented (in Vitamin B12 or folate deficiency). |
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Three types of Neutrophilgranules |
•Primary (azurophilic) granules •Secondary (specific) granules •Tertiary granules: |
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Seven primary (azurophilic) granules |
1.Acidphosphatase 2.Myeloperoxidase 3.Phospholipase A2 4.Lysozyme 5.Elastase 6.Defensin 7.Bacterialpermeability increasing protein (BPI) |
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Six Secondary (specific) granules |
1.Leukocytealkaline phosphatase(LAP) 2.Phospholipase A2 3.NADPHoxidase 4.Collagenase 5.Lactoferrin 6.Lysozyme |
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Tertiary granules |
–Phosphatasesand metalloproteinases (gelatinases& collagenases) |
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Neutrophilstained for peroxidase (EM) |
Thesmall, pale, peroxidase-negative specific granules andthelarger, dense, peroxidase-positive azurophilicgranules. |
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Amount of Neutrophils in normal conditions |
•Undernormal conditions, 90% of the neutrophilsare in the bone marrow, 2–3 % are circulating and the rest are in the tissues. |
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What type of environment do Neutrophils survive in ? What is its advantage? |
Neutrophils to survive in an anaerobic environment is highly advantageous, since they can kill bacteria and help clean up debris in poorly oxygenated regions, eg, inflamed or necrotic tissue. • |
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Neutrophils life span |
•Neutrophils are short-lived cells with a half-life of 6–7 hr in blood and a life span of 1–4 days in connective tissues, where they die by apoptosis. |
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Function of Neutrophils |
Neutrophils are the body's first line of defense against infection by bacteria/inflammation (seen at the site of injury within first 24 hours). |
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Margination of Neutrophils |
- Neutrophils have selectin molecules on their outer surface; these selectins bind to selectin receptors on the endothelial cells of blood vessels, allowing the neutrophils to slowly "roll" along the endothelial lining (margination). |
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How do Neutrophils respond to specific inflammatory signals? |
In response to specific inflammatory signals from the surrounding tissue (e.g. from basophils and mast cells), the neutrophil will express specific membrane integrins; these bind to integrin receptors on the endothelial cells, anchoring the neutrophil. |
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Diapedesis (Neutrophils) |
Neutrophilmigrates between endothelial cells by an ameboid process called diapedesis, crossing theendothelial wall and entering the surrounding C.T. |
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Migration of neutrophil |
Migration of neutrophil from postcapillary venule into the connective tissue |
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Function of Phagocytosis |
•Thefinal step in Phagocytosis ofmicrobes is killing and degradation. |
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How are phagocytic cells mediated? |
Mediated within phagocytic cells by: 1.Oxygen dependent and 2.Oxygen independent mechanisms |
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Oxygendependent microbial killing |
•Phagocytosisinitiates activity of the HMP shunt, causing an oxidative burst and supplyingelectrons to an NADPH oxidase inthe phagosomalmembrane. •Productof the NADPH oxidasereaction is superoxide,whichis further converted to hydrogen peroxideby disputation. •Hydrogenperoxide maybe further converted to the activated hydroxyl radicals. Hydrogen peroxidealone is insufficient. •MPO(azurophilicgranules) converts hydrogen peroxide to HOCl- (in presence of Cl- ), an oxidant/antimicrobialagent. |
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Chronicgranulomatous disease of childhood (CGD) |
•Patientswith chronic granulomatousdisease have a deficiency of NADPH oxidase,which results in an inability of neutrophils togenerate hydrogen peroxide (respiratory burst). This limits the ability of the neutrophil tokill bacteria. - Catalase positive (Stapylococcus aureus) organisms |
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Catalase positive (Stapylococcus aureus) organisms |
- ingested but not killed. H2O2 not available as a substrate for MPO. –Catalase degrades the small amounts of H2O2 produced by the infecting microbes, allowing them to survive within the phagosome. |
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Catalase negative (Streptococci) organisms: |
generate and maintain sufficient amounts of H2O2 from which other highly reactive compounds are produced within the phagocytic vacuole of the CGD neutrophils and macrophages, leading to effective microbial killing. |
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Test for Chronic granulomatous disease of childhood (CGD) |
–Nitroblue tetrazolium (NBT) dye test-> negative |
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Amount of Eosinophils in normal blood and two type of granules |
•2–4% in normal blood. 2–15 mm in diameter and a bilobednucleus. - Specific granules - Azurophilic granules |
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Azurophilic granules (Eosinophilic) |
contain lysosomal acid hydrolases and hydrolytic enzymes that function in destruction of parasites and hydrolysis of antigen–antibody complexes internalized by the eosinophil. |
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Specific granules (Eosinophilic) |
- refractile, large and elongated (about 200 per cell) - have a crystalline core (internum). •Theless dense material surrounding the internum isknown as the externum, ormatrix. |
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Crystalline core in specific granules contain four proteins: (Eosinophilic) |
1.Majorbasic protein (MBP), forthe intense acidophilia ofthe granules. 2.Eosinophilcationic protein (ECP) 3.Eosinophilperoxidase (EPO) 4.Eosinophil-derivedneurotoxin (EDN) |
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Majorbasic protein (MBP) |
•Presentin the crystalline core of eosinophilic specific granules. •Richin arginineand lysine residues. •Constitutes50% of the total granule protein. •Accountsfor the eosinophilia ofthese granules. •Functionsin the killing of parasitic worms. |
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Functions of Eosinophil |
•Phagocytosisof antigen/antibody complexes in asthma,hay fever and other allergies. •Destructionof invading parasites -Eosinophil numbers rise sharply during allergic reactions or parasiticinfections. •Counteractingthe effects of basophils -These modulate inflammation by inactivating the leukotrienes and histamineproduced by other cells. –Histaminase -anti-histamine –Arylsulfatase(which neutralizes leukotrienes secretedby basophils and mast cells) |
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Basophils |
•Lessthan 1% of blood leukocytes. Bilobednucleus, usually obscured by numerous denselybasophilic(deep blue) specific granules. •Structuraland functional similarities with tissuemast cells. •Thebasophilplasma membrane possesses numerous high-affinity Fcreceptors for IgEantibodies. •Rapiddegranulationcausing asthma attack or urticaria oreven anaphylactic shock. |
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Basophil Specific granules contain: |
–Heparin –Histamine,a potent vasodilator and causes smooth muscle contraction in bronchi. –Leukotrienes or Slow-Reacting Substance of Anaphylaxis (SRS-A),forthe slow, sustained contraction of smooth muscle. |
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Basophil Primary granules |
arelysosomes ofbasophilcontain lysosomalacid hydrolases. |
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Characteristics of Lymphocytes |
•Lymphocytesare characterized by a round, densely stained nucleus and a small amount ofpale basophilic, non-granular cytoplasm. • |
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Lymphocytes are the only type of leukocytes that do what? |
•Lymphocytes are the ONLY type of leukocytes that return from the tissues back to the blood and under proper stimulation by cytokines, will continue to divide outside the marrow. |
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What do Large' lymphocytes represent? |
'Large' lymphocytes represent activated B or T lymphocytes. |
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Types of Lymphocytes |
- B Lymphocytes - T Lymphocytes - Natural Killer (NK) cells |
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Examples of B Lymphocytes |
- B cells - Plasma cells - Memory B-cells |
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Examples of T Lymphocytes |
- Helper - Cytotoxic - Suppressor - Memory T- cells |
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Monocytes |
•Monocytesare the largestof the white cells(up to 20 μm indiameter) and constitute from 2 to 10% of leukocytes in peripheral blood. •Theyare motile phagocytic cells and are the precursors of macrophages found inperipheral tissues and organs. |
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Nucleus of Monocytes |
–Large, eccentrically placed; nuclear indentation tends to become more pronounced as the cell matures, so as to give a kidney shape appearance. |
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Cytoplasm of Monocytes |
–Greyish blue, contains numerous lysosomal granules and cytoplasmic vacuoles which gives a 'frosted-glass' appearance. |
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Monocytes respond by __________ to the presence of factors from damaged tissue, microorganisms and inflammation. |
Monocytesrespond by chemotaxis tothe presence of factors from damaged tissue, microorganisms and inflammation. |
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Major Function of Neutrophils & Type |
Function: Kill and phagocytose bacteria (pathogens and cellular debris) Type: Granulocytes |
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Major Function of Eosinophils & Type |
Function: Kill helminthic and other parasites; modulate local inflammation (use granule contents to digest large pathogens, such as worms and reduce inflammation) Type: Granulocytes |
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Major Function of Basophils & Type |
Function: Modulate inflammation, release histamine during allergy (promote blood flow to injured tissues and inflammatory response) Type: Granulocytes |
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Major Function of Lymphocytes & Type |
Function: Effector and regulatory cells for adaptive immunity (responsible for specific immunity such as B cells that produce antibodies and T cells that destroy cancer and virus-infected cells) Type: Agranulocytes |
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Major Function of Monocytes & Type |
Function: Precursors of macrophages and other mononuclear phagocytic cells (become macrophages that phagocytize pathogens and cellular debris) Type: Agranulocytes |
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Platelets |
•Nonnucleated,disk like cell fragments 2–4mm in diameter. •Plateletsoriginate from the fragmentation of giant polyploid megakaryocytesthat reside in the bone marrow. •Megakaryocytes arise in turn from megakaryoblasts bythe process of endomitosis, inwhich nuclear division occurs without cytoplasmicdivision and the nucleus will become polyploid. |
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How do Platelets appear in blood smears? |
In stained blood smears, platelets appear in clumps. |
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Hyalomere region of Platelets |
• a peripheral,light-stainingregion filled with microtubules and microfilaments –Asystem of canaliculithat open to the surface aids indelivering the granule contents to the outside. •Marginal bundle of microtubules •Actin and myosin molecules |
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Marginal bundle of microtubules (Hyalomere region of Platelets) |
–helps to maintain the platelet's ovoid shape. |
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Actin and myosin molecules (Hyalomere region of Platelets) |
–functions in platelet movement and aggregation. • |
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Granulomere region of Platelets |
• a central,densely staining region marked by granules of various sizes –Alpha(α)granules(largest) –Delta(δ)granules(mid-size) –Lambda(λ)granules(smallest) |
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Alpha (α) granule (Granulomere region of Platelets) |
Alpha (α) granules (largest) contain platelet-derived growth factor, thromboplastin, von Willebrand's factor VIII, fibrinogen, and factor V. |
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Delta (δ) granules (Granulomere region of Platelets) |
Delta (δ) granules (mid-size) contain ADP, ATP, and serotonin. |
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Lambda (λ) granules (Granulomere region of Platelets) |
Lambda (λ) granules (smallest) contain lysosomal enzymes. |
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Roleof platelets in controlling bloodloss(hemorrhage) and in wound healing |
•Injuryof small vessels (e.g., capillaries, venules)is followed by adherence of platelets to the injured endothelium and theiraggregation to form platelet plugs bound together by fibrin strands (thrombi). - vonWillebrand'sfactor VIII - Adenosine diphosphate - Thromboxane A2 |
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von Willebrand's factor VIII |
which is produced by both megakaryocytes and endothelial cells, mediates platelet adhesion. – |
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Adenosine diphosphate |
which promotes platelet aggregation, is released from platelet delta (δ) granules after adhesion occurs. |
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Thromboxane A2 |
a potent aggregating and vasoconstricting agent, is synthesized by platelets after the initial release reaction. |
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Von Willebrand's disease (vascular hemophilia) |
is caused by a genetic defect that results in reduced synthesis of von Willebrand's factor (vWF) by endothelial cells and platelets. Sudden nosebleeds and bleeding from the gums occur in severe cases. |
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Whitecell count in disease: neutrophils |
•Raisedneutrophil count (neutrophilia)indicates an acute inflammatory response and is seen in bacterial infections. • |
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White cell count in disease: eosinophil |
•Raised eosinophil count (eosinophilia) is seen in response to allergy and in infections with certain parasites. • |
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White cell count in disease: lymphocyte |
•Raised lymphocyte count (lymphocytosis) is seen in response to viral infections. • |
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White cell count in disease: Malignant tumors |
•Malignant tumors can form from the bone marrow cells that make white blood cells, termed leukemias. In these conditions it is common to find a very raised white cell count corresponding to circulating malignant cells. |
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White cell count in disease: Reduction in white cells |
•Reduction in white cells in the blood may indicate defective function of the bone marrow. |
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Anemia |
•Anemiais the condition of having a concentration oferythrocytes belowthe normal range. Tissuesareunable to receive adequateO2. •Anemia may result from insufficient red cell production, due to iron deficiency, or from blood loss with a stomach ulcer or excessive menses. |
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Symptoms of Anemia |
Symptoms: lethargy, shortness of breath, fatigue, skin pallor, and heart palpitations. |
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Polycythemia (Erythrocytosis) |
- An increased concentration of erythrocytes in blood. It may be a physiologic adaptation in individuals who live at high altitudes, where O2 tension is low. |
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Investigations of Anemia |
•Hemoglobinestimation •PeripheralBlood Smear –Anisocytosis(Variation in size) • Macrocytes –Megaloblasticanemia • Microcytes –Irondeficiency and thalassemia –Poikilocytosis(Variation in shape) –Hypochromasia |
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Iron deficiency Anemia |
•Irondeficiency –microcytic hypochromic anemia –Resultsfrom inadequateiron intake, excessive iron lossdue to chronic hemorrhage (peptic ulcer, tumor, etc.) or increasediron demands(i.e., pregnancy) –↓RBCcount & Htc –RBCare microcytic and hypochromic and increased central area of pallor. –Pallor,brittle nails and oral lesions. |
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Megaloblastic anemia |
•Deficiencyof vitamin B12, folic acid or IF (i.e.,atrophic gastric mucosa, pernicious anemia) – megaloblastic anemia –Maturationfailure |
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Maturation failure in Megaloblastic anemia |
•→ ↓ rate of erythroblasts proliferation. •→ production of large precursor cells – megaloblasts and larger irregular oval erythrocytes – macrocytes fully saturated with Hb – macrocytic (megaloblastic) anemia •→ ↑ fragility of the plasma membrane → ↓ life span → anemia. •Hypersegmented neutrophils |
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Sickle cell anemia |
•Inheriteddisorder caused by a mutation of onenucleotide (pointmutation)in the DNA of the gene for the β-chainof hemoglobin. •Mutation causes formation of HbS instead of HbA –HbS– HbαA2βS2 (AAvaline is substituted for glutamic acid at position 6 in the βchain) –HbSprecipitates into long crystals when oxygen tension is low(hypoxia) → cell elongation (sickling) and damage to the cell membrane →hemolysis → hypoxia (vicious cycle). •Jointpain, abdominal pain, jaundice & Salmonella osteomyelitis. |
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Sickle cell disease |
The gene responsible for sickle cell disease alters the permeability of the RBC membrane → ↑ leakage of K+ from the RBC →↑ resistance to malaria parasites. |
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How do the sickled cells decrease blood flow |
•RBC'sshape - long, thin sickle forms. •Thesickled cells are prone to stick together, plugging smaller vessels and leadingto decreased blood flow with ischemia |
