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110 Cards in this Set
- Front
- Back
Where does the blood cells arise in the early embryo (2-8 weeks)?
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Yolk sac (mesoderm) produces blood islands
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Where does hemopoiesis occur during 2nd trimester - birth?
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Mainly in the liver, spleen plays a minor role too
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Where does hematopoiesis occur during 3rd trimester - adulthood?
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Bone marrow
*Hematopoiesis in post-natals is exclusively in the bone marrow |
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Structure of the bone marrow:
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Reticular fibers
Veins Arteries Sinusoids Island of cells (Blood sinusoids appear white) |
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The two types of bone marrow include?
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Red marrow: active hematopoiesis
Yellow marrow: fat in reticular cells, inactive hematopoiesis |
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Production of blood cells include:
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* >10^9 (billion) cells produced daily
All blood cells arise form a single major type of pluripotent stem cell in the bone marrow * As cells develop, they decrease in size, nuclei condense |
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Stem cells forms 2 major lineages of progenitor cells, which are the...?
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Myeloid cell: colony forming units
Lymphoid cell (Lymphocytes): colony forming units *Both types are multipotential cells |
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The myeloid lineage includes:
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Precursor cells (blasts) for:
erythropoiesis thrombopoiesis granulopoiesis monocytopoiesis *All in the Bone Marrow |
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The lymphoid lineage forms...
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Lymphopoietic cells
T Lymphocyte B Lymphocyte --> Plasma cell NK lymphocyte *Partly in the bone marrow & partly in Lymphoid organs |
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What is the difference between progenitor cells and precursor cells?
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Progenitor cells (colony-forming units) are committed to a single cell line with limited self renewal ability
Precursor cells (blasts) are morphologically distinct, No self renewal |
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What is the regulation for hematopoiesis ?
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1. hematopoietic growth factors (colony stimulating factors)
2. interleukins, granulocyte colony stimulating factor, erythropoietin 3. stem cell factor (steel factor) - stromal cells of the bone marrow, stimulates division 4. hematopoietic cells will die unless exposed to grown factors |
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Erythropoiesis is controlled by?
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Cytokines and Erythropoietin (kidney)
takes ~ 3-5 days to complete development ~ 2 x 10^9 erythrocytes per day |
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Identify this cell
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Proerythroblast (Erythropoiesis)
14-19 um No hemoglobin Large nucleus Basophilic cytoplasm |
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Basophilic (early) erythroblast (Erythropoiesis)
12-17 um some Hemoglobin Condensing nucleus |
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Polychromatophilic erythroblast (Erythropoiesis)
12-15 um "muddy" cytoplasm |
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Orthochromatophilic (late) (Erythropoiesis)
8-12 um increased hemoglobin |
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Reticulocyte (Erythropoiesis)
7-8 um No nucleus some Ribosomes (blue with Cresyl Blue stain) |
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Erythrocyte (Erythropoiesis)
7.5 um Only Hemoglobin No Ribosomes |
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Reticulocytes
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What are the arrows pointing to?
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Identify this cell
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What does Granulocytopoiesis (granulocyte formation) include and what controls it?
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Controlled by cytokines, takes ~11 days
1. Myeloblasts 2. Promyelocyte 3. Myelocyte 4. Metamyelocyte 5. Band 6. Mature form |
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What cell is this?
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Myeloblasts (Granulocytopoiesis)
Common precursor 12-14um No Granules Cytoplasmic blebs |
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Promyelocyte (Granulocytopoiesis)
16-24um large Nucleus Azurophilic granules (not specific) |
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Myelocyte (Granulocytopoiesis)
10-12 um condensed rounded nucleus specific granules |
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Metamyelocyte (Granulocytopoiesis)
Kidney-shaped nucleus specific granules |
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Mature form of granulocytes include:
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Neutrophil
Eosinophil Basophil "BEN" |
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Identify this cell
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A neutrophil with a segmented nucleus
*Neutrophils may be subdivided into segmented neutrophils (or segs) and banded neutrophils (or bands). |
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Characteristics of Band (stab) granulocytes are:
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C-shaped nucleus
specific granules *Before neutrophilic granulocyte reaches its complete maturation, it passes through an intermediate stage --> Band (Stab) cell |
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Identify these cells
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What is Thrombopoiesis and what controls it?
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= Platelet formation
Controlled by Thrombopoietin |
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What are some of the important components for thrombopoiesis?
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1. Megakaryoblast (25-40 um, endomitosis, polyploid ~32N)
2. Megakaryocyte (40-100 um, large multi-lobed nucleus) 3. Platelet demarcation membranes 4. Proplatelets |
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What is the function of megakaryocyte?
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It is a bone marrow cell responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting
*Platelets are formed from fragments of megakaryocyte cytoplasm |
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What are platelet demarcation membranes?
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They are mature megakaryocytes that have numerous invaginations of plasma membrane ramifying throughout the cytoplasm
This membrane system (D) is a reservoir of membrane used during elongation of the numerous proplatelets which extend from the megakaryocyte surface |
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What are proplatelets?
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The elongated branching processes extended from megakaryocyte cytoplasm --> to form platelets
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Identify this cell
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Identify this cell
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Process of Monocytopoiesis (Monocyte formation) includes:
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1. Monoblasts (large, undifferentiated)
2. Promonocytes (16-18um, kidney-shaped nucleus, azurophilic granules) 3. Monocytes ("sky" blue cytoplasm, kidney-shaped nucleus) 4. Macrophages (when entered the circulation) |
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Process of Lymphopoiesis (lymphocyte formation) includes:
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1. colony forming units (CFU) - lymphocytes (B & T)
2. Lymphoblasts: Large, undifferenciated 3. Prolymphocytes: medium-sized cells, condensing chromatin, No cell surface antigens |
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How are T-cells (T lymphocytes) made?
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When hematopoietic progenitor cells migrate from bone marrow to thymus
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How are B-cells made?
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When hematopoietic progenitor cells remain in the bone marrow, they differentiate to B-cells migrate to lymph tissues
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What is Pancytopenia?
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= a medical condition in which there is a reduction in the number of red and white blood cells, as well as platelets
*Due to failure of bone marrow to produce blood cells |
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What are the two approaches used to identify causes of bone marrow failure?
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1. Consider causes of peripheral destruction: hypersplenism, sepsis, immune-mediated
2. Perform bone marrow investigation a. Hypercellular marrow b. Hypocellular marrow |
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Hypercellular marrow may indicate:
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Peripheral destruction
Hypersplenism MDS Marrow infiltration Hematologic malignancy (Solid tumor; Storage disease; other) Megaloblastic anemia Myelofibrosis |
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Hypocellular marrow may indicate:
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Aplastic anemia
Drugs/chemicals Viruses Radiation Fanconi anemia Idiopathic |
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What are storage diseases?
Examples? |
--> affect bone marrow (and other tissues)
Most common bone marrow storage disease are: Gaucher's disease Niiemann-Pick disease |
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What cause Gaucher's disease?
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Due to Deficiency of the enzyme Glucocerebrosidase
(helps body process the fatty substance glucocerebroside) |
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When does Gaucher's disease occur?
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When certain harmful fatty substances accumulate to excessive levels in the liver, spleen, lungs, bone marrow, and brain (less common)
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What is Niemann-Pick disease?
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Congenital deficiency in lysosomal sphingomyelinase.
Results in Sphingomyelin, cholesterol and glycolipid accumulation in macrophages in liver, spleen, bone marrow, hepatocytes, and CNS cells |
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What is Myelodysplastic syndrome?
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A group of disorders caused by poorly formed or dysfunctional blood cells
NO CURE! Can only prolong life when treated with bone marrow transplant |
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What is Fanconi anemia (FA)? and what is the outcome?
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Rare, Inherited blood disorder that leads to bone marrow failure.
FA prevents the bone marrow from making enough new blood cells FA can cause to make many faulty blood cells *Result in serious health problems, eg. Leukemia |
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Multiple myeloma is?
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Cancer of plasma cells
(Plasma cells normally make antibodies) |
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Viruses that suppresses immune system are:
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Parovovirus B19
Dengue Hepatitis viruses Epstein-Barr virus Cytomegalovirus Human Immunodeficiency Virus (HIV) |
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Pancytopenia can result in which 3 things?
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Increased destruction --> Immune destruction sepsis
Sequestration --> Hypersplenism Decreased production --> Myelodypalsia; Marrow infiltrate; B12 deficiency; Aplastic anemia; Drugs; Viruses; Radiation |
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Defective RBC formation may result in?
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Anemia
Hemorrhage Deficient erythropoiesis Accelerated destruction of circulating RBCs Deficiencies of Fe, Vit. B12, Folic acid |
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Defective WBC formation may result in?
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Inflammation
Allergic rxn Hypersensitivity rxns Infections Leukemia |
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4 Main types of Leukemia are:
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1. Acute lymphoblastic leukemia (ALL) --> mostly children
2. Acute myelogenous leukemia (AML) --> both children and adults 3. Chronic lymphocytic leukemia (CLL) --> mostly adults >55 yo; rare in children 4. Chronic myelogenous leukemia (CML) --> mostly in adults |
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Defective platelets formation may lead to?
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Bleeding problems (increase / decrease)
Thrombocytosis (or thrombocythemia) --> due to high platelet counts in blood Thrombocytopenia --> decrease of platelets in blood |
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Identify all the cells.
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Blue arrow = Myelocyte
Yellow arrow = Metamyelocyte Black arrow = Neutrophil |
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Blood
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Specialized connective tissue
o Cells o Matrix • Ground substance • Fibers |
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Blood CT
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Matrix --> Plasma
No fibers (differentiates from other CT) |
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Bone marrow
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All of the several blood cell types originate in the BM
WBC (Lymphocytes and monocytes) --> Move freely back and forth between blood and other connective tissues |
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Plasma
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Aqueous Solution
•7% protein Albumin --> Maintains osmotic pressure of blood Gamma globulins -->Immunoglobulins or antibodies Fibrinogen --> Clotting agent 10% lipoproteins •Amino acids •Vitamins •Hormones •Inorganic salts |
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Formed elements
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Cells
Platelets |
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Blood component:
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RBC = Erythrocytes = 44%
WBC = Leukocytes and platelets = 1% Plasma = 55% |
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Blood smears used
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Leishman
Wrights Giemsa or May-Grunwald-Giema stains Modified Romanowski Stain! Methaline blue and eosin |
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Red blood cells – erythrocytes
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Biconcave discs
Non-nucleated Acidophilic (Stained reddish with eosin) Main protein = Hemoglobin + O2 = Oxyhemoglobin 120 day life span Males has more blood count than females (menstruation) Carbonic anhydrase (CO2 transportation) Enzyme of glycolytic and HMP shunt pathways ABO blood group system Rh antigens ‑ Rh+ vs Rh‑ |
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Most common blood type
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Type O,
A B AB |
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Universal donor
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Type O
No antigens = no clumping |
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Universal recipient
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Type AB
No antibodies = no clumping |
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How does blood typing work?
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Whatever type blood a person is, that’s the antigen present on their blood…
- Example, if your blood type is A, you have A antigen on it - Type B = Type B antigen - TYPE O has NO ANTIGEN If someone was Type A blood, they would have A antigen and have B antibodies on their blood - Type B, as type B antigen, and A antibodies … - Type AB has NO ANTIBODIES |
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Rh System
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Rh positive = antigen present, no antibodies
Rh negative = no antigen present, antibodies will be produced IF exposure occurs Erythroblastosis fetalis (also called Rh disease) --> Rh negative mother & Rh positive father have an Rh positive fetus Rhogam = passive immunity (treatment for Rh disease) |
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Clinical applications
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-Erythrocyte membrane deformation – cytoskeletal organization "Spectrin"
-Anisocytosis (abnormal variation in cell size (macro and microcytosis) -Poikilocytosis (altered cell shape (sickling, crenation) |
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Hemoglobin
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Composed of globin
4 highly folded polypeptide chains 4 heme groups with iron Each molecule carry 4 moles of oxygen Oxyhemoglobin Reduced hemoglobin when not carrying oxygen Can carry carbon dioxide |
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Sickle Cells
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-Single point mutation that codes for globin produces HbS hemoglobin with a single amino acid difference at point 6 on the B chains
-Substitution of hydrophobic valine for hydrophilic glutamic acid -Valine is in sickled gene |
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White Blood Cells – leukocytes
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Granulocytes
Neutrophils Eosinophils Basophils Agranulocytes Lymphocytes Monocytes |
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Types of blood cells from most to least amount.
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NEVER LET MONKEY EAT BANANA’s
- Neutrophils ~60% (50-70%) - Lymphocytes ~30% (20-40%) - Monocytes ~5% (1-9%) - Eosinophils ~3% (0-5%) - Basophils ~0.5% (0-2%) |
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Granulocytes
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-Irregular segmented nuclei
-Specific granules (specific size, staining affinities, ultrastructure) -Terminal (fully differentiated) cells |
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Agranulocytes
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-Regular nuclei (round or kidney-shaped)
-Non-specific granules |
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Processes exhibited by Leukocytes
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Chemotaxis
Amoeboid movement Diapedesis Neutrophils Eosinophils |
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Chemotaxis
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Chemical attraction which stimulates WBC (esp Neutrophils and monocytes) to sites of infection
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Amoeboid movement
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WBC motility in which pseudopodia are extended and the rest of the cell pulled forward in “crawling” action
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Diapedesis
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WBC flatten and move through the vascular wall into the interstitial tissue
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Neutrophils
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also called neutrophilic granulocytes / polymorphonuclear neutrophilic leukocytes, PMNs, or polys
= most numerous of the leukocytes ~60% of the WBC count Twice the size of RBC |
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What are the characteristics of Neutrophils?
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Very characteristic nucleus
Divided into 3-5 lobes connected to thin strands of chromatin Lobes can increase with cell age (up to 7) = hypersegmented cells |
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The 2 types of granules of Neutrophils are:
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1. Primary (A) granules
Contain Lysosomal enzymes 2. Secondary (B) granules Contain enzymes with strong bactericidal actions *Granules of neutrophils are weakly stained |
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Function of the Neutrophils:
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•Inflammatory process
•Invades sites of infection in response to cytokines, released by cells invading infection sites •First to come to invading site •Receptors in plasma membrane allow them to recognize and phagocytosize and destroy •Tags with antibodies (or opsonized) •Cannot replenish their store of granules •Cell dies once their supply of granules has been exhausted. Dead neutrophils and tissue debris are the major components of pus •Life span is 1 week |
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Eosinophils
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10-15 um
2 lobes Short life span (few days) Granules |
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Granules of Eosinophils include:
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Specific and non-specific (azurophilic/acidophilic)
a. Specific: large granules (crystalloid-major basic protein, enzymes) b. Non-specific: lysosomes; hydrolytic enzymes |
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Function of Eosinophils:
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1. Destroy antibody‑antigen complexes and parasitic worms
2. Release major basic protein involved in killing parasites 3. Engulf and destroy antibody‑antigen complexes |
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Basophils
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8-12 um
less than 0.5-1% of leukocytes Granulocytes Have 2 or 3 lobed nucleus S shaped Not well defined nucleus Granules are stained bluish or reddish-biolet Granules |
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Granules of Basophils include:
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Specific
• Large granules (heparin, histamine, leukotriene) Non-specific (azurophilic) • Lysosomes, hydrolytic enzymes |
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Functions of Basophils:
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•Heparin and histamine (vasoactive substances)
•Dilate blood vessels, make vessel walls more permeable and prevent blood coagulation •Facilitate access of other lymphocytes and plasma-bourne substances of importance for the immune response (antibodies) to a site of infection •Release of the contents of the granules of basophils is receptor-mediated •Antibodies produced by plasma cells (activated B lymphocytes) bind to Fc Receptors on the plasma membrane of basophils |
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Mast cells:
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1. binding of antigens (to IgE) releases specific granules
2. histamine ‑ vasodilation, smooth muscle contraction, etc. 3. heparin ‑ anticoagulant |
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Identify cells
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Monocytes:
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12 ‑ 25 um
Kidney or C shaped nucleus No specific granules Pale blue cytoplasm Life span (few days in circulation/months in tissues) Granules: non-specific (azurophilic) - lysosomes |
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Functions of Monocytes:
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become tissue macrophages after migration
1. avid phagocytes (dead cells, antigens, bacteria) 2. produce cytokines ‑ initiate inflammation, etc. 3. antigen‑presenting cells 4. foreign body giant cells (multinucleated) |
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Lymphocytes
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8-18 um
Lifespan (Months to years) Round, dense nucleus No specific granules Small, blue cytoplasm Granules: non‑specific (azurophilic) – lysosomes Immune response |
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Function of Lymphocytes
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immune response (B cells, T cells, null cells)
1. B cells become plasma cells ‑ produce antibodies 2. T cells kill viral cells, produce cytokines 3. null cells ‑ stem cells, natural killer cells |
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Platelets:
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2-4 um
No nucleus Cell fragments from megakaryocyte Hyalomere (Outer region hardly stains, peripheral tubuler system, increase surface area) Granulomere (Dense core with granules and few organelles, stains bluish) Granules Count: 250,000 ‑ 500,000 |
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Granules of Platelets include:
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alpha, delta, lambda (lysosomes)
a. alpha: fibrinogen, platelet derived growth factor, [PDGF]etc. b. delta: calcium, serotonin, ATP, etc. c. lambda: lysosomal (hydrolytic) enzymes |
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Function of Platelets:
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-Assist in hemostasis (arrest of bleeding)
-Damaged vessels …walls and platelets secrete substances to mediate the conversion of the plasma protein prothrombin into thrombin. Thrombin catalyzes the conversion of fibrinogen into fibrin, which polymerizes into fibrils and forms a fibrous net in the arising blood clot -Platelets captured in the fibrin net contract leading to clot retraction |
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Intrinsic pathway
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-XII gets converted by HK/PK to XIIa
-XI gets converted by Ca2/HK to XIa -IX gets converted by CA2 to IXa ... |
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Platelet function:
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1. circulating platelets; endothelial damage
2. platelet adhesion 3. platelet aggregation 4. platelet-fibrin plug 5. clot retraction |
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Some Anomalies:
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Inappropriate clotting
Excessive bleeding |
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Inappropriate clotting due to:
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a. thrombus - clot formed in an intact vessel, possibly due to:
roughened vessel walls (atherosclerosis) slow-moving blood (e.g., in varicose veins) = small quantities of fibrin form & accumulate b. embolus - 'moving' clot |
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Excessive bleeding due to:
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a. Hemophilia
genetic "defect" inability to produce certain factor(s) b. Thrombocytopenia abnormally low platelet count most persons have idiopathic thrombocytopenia (= unknown cause) in others it's an autoimmune disease |