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Blood
Circulating Blood & Hematopoiesis
43
Biology
Graduate
10/13/2008

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Term
Blood
Definition
A fluid suspension of plasma and cells, which flow to and from every organ, in vessels lined with endothelial tissue. Often considered specialized connective tissue.
Term
Hematocrit
Definition
Normal blood composition, which is ~54% plasma, 45% RBCs, and 1% white cells.
Term
Normal adult blood volume
Definition
70 ml/kg body weight, or 5 liters total
Term
Plasma
Definition

Proteins synthesized mainly by the liver, and ions and water whose levels are controlled by the kidneys. Albumin is major serum protein. Plasma can clot, and fluid remaining after is called serum.

Term
Albumin
Definition
Major serum protein, which contributes significantly to the osmolarity of the blood and carries hydrophobic molecules in the blood.
Term
Formed elements
Definition
Cells produced primarily in bone marrow, but function elsewhere (therefore blood is known as a discontinuous tissue)
Term
# RBCs/ml
Definition
5-10 billion
Term
#White cells/ml (leukocytes=granulocytes + agranulocytes)
Definition
5-7 million
Term
# Platelets/ml in blood
Definition
200-400 million
Term
Romanovsky mixtures
Definition
Stains usually employed for clinical examination of blood smears. Includes Wright, Giemsa, or May-Grunwald stains.
Term

Eosinophilic Stain

Definition
Red to Orange in color. Also known as acidophilic
Term
Basophilic Stain
Definition
Purple to Black in color
Term
Neutrophilic stain
Definition
Pink to Tan in color
Term
Polychromatophilic stain
Definition
Blue-gray in color
Term
Size of an Erythrocyte (RBC)
Definition
7-8 um
Term
Shape of Erythrocyte
Definition
Biconcave disc, which allows for easy deformability, provides high surface to volume ratio, and results in lighter staining in the center of the cells. Frequently into stacks called rouleaux.
Term
Rouleaux
Definition

Poker chip-like stacks of RBCs

Term
Band 3 (anion transport protein) and glycophorin
Definition

Proteins in the RBC cell membrane responsible for anchoring the peripheral protein network (aka cytoskeleton).

Term
RBC cytoskeleton
Definition
Proteins called band 4.1 link short actin filaments to spectrin tetramers, and spectrin-actin complex is linked by two integral membrane proteins- to band 3 by ankyrin and to glycophorn by band 4.1. This membrane cytoskeleton linkage determines shape of the cell and stabilizes the lipid bilayer.  
Term
Aquaporin
Definition
Facilitates water movement into RBCs/cells in general.
Term
RBC cytoplasm
Definition
Consists mostly of Hemoglobin (Hb), which is a heme containing protein that functions to carry oxygen via the iron containing heme group. Carbonic anhydrase catalyzes formation of carbonic acid from CO2, which dissociates to bicarb, facilitating movement of 80% of CO2 back to the lungs. Band 3 facilitates movement of bicarb across the plasma membrane of RBCs in exchange for Cl-. No organelles in a normal RBC and energy is from glycolysis.
Term
Function of RBCs
Definition
Serves as a container for hemoglobin
Term
Anemia
Definition
Recution in hemoglobin per volume of blood. Caused by decrease in cell number, size, or amount of Hb per cell. Leads to increased RBC production
Term
Polycythemia
Definition
Increase in hematocrit/# RBCs/ml. Can result from low oxygen stress, such as high altitude or lung disease. Causes "thick blood" to form, which has trouble travelling through capillaries.
Term

Sickle Cell Anemia

Definition
Genetically tranmitted disease resulting from altered Hb gene (Hb S), which is less soluble when deoxygenated and may polymerize and stick to membrane, leading to influx of calcium and "sickling" of cells. Death can result from heart disease or thrombosis.
Term
Thalassaemia
Definition
Inherited alteration in synthesis on either alpha or beta chain of Hb. Overproduction of one leads to precipitates, which can bind to membrate and decrease fluidity (Heinz bodies). Results in massive destruction of RBCs by the spleen and stimulates the marrow to overproduce RBCs. Skull enlargement may result.
Term
Hereditary spherocytosis (HS)
Definition
Autosomal dominant disease. RBCs have low surface to folume ratio and cannot form biconcave discs, leading to destruction by spleen and anemia. Cytoplasmic calcium concentrations are high and spectrin is over phosphorylated.
Term
Granulocyte
Definition
Leukocytes which are microphages and contain specific granules involved in killing functions that protect against invading infective cells, principly bacteria.
Term
Polymorphonuclear Neurtophils (PMNs)
Definition
Most numerous white cell (4.4 million/ml), involved in defense against bacterial infection. 10-15 um diameter, inactive and basophilic nucleus divided into 2-5 lobes connected by thin filaments. Granules are membrane bound organelles similar to lysosomes and peroxisomes, used to destroy bacteria.
Term
Primary and secondary granules
Definition
Present in PMNs. Primary granules do not stain in mature cells and are azurophilic in immature cells. They are large, dense, and contain peroxidase, lysozyme, and myeloperoxidase. Secondary granuales are specific to PMNs and are neutrophilic. Less dense and contain a variety of antibacterial agents such as lactoferrin, lysozyme, cationic compounds, peroxides, and oxygen radicals, and enzygems for generating iodide.
Term
Chemotaxis
Definition

First step in microbe destruction with PMNs. Surface receptors with specific binding sites for molecules involved in inflammation. Such molecules, upon binding, stimulate PMNs to move toward higher concentrations. Initial movements involved marginated cells in venules or capillaries leaving blood stream and entering tissue (diapedesis-to leap between). May be stimulated by interaction of adhesion molecules (selectins and integrins and their ligands) expressed on surface of PMNs and endothelial cells, which respond to inflammatory signals.

 

Once in a tissue, PMNs follow gradietns of chemotactic factors generated by inflammatory agents (ie C5a, cytokines, arachidonic acid metabolites, bacterial petides containing N-formylmethionine, and other factors released by WBCs at site of infection. One of these factors is released by PMNs enfulfing uric acid crystals seen in gout, leading to gouty arthritis.

Term
Phagocytosis
Definition

Second part of PMN destruction of microbes. Membrane of PMN surrounds and encloses microbe, likely involving integral membrane protein receptors and movements of cytoskeleton

Term
Killing
Definition
3rd part of destruction of microbes by PMNs. Fusion of PMN granules with membrane surrounding the microbe releases the granule contents and initiates the many killing reactions of PMNs. Results in pus when PMNs die due to vigrous attack on microbe.
Term
Inflammation
Definition
4th part of PMN microbe destruction. Killing factors released by PMNs as they attack microbes, cytokines released by other WBCs and resident tissues, and factors from invading organisms themselves contribute to inflammation. ECM is depolymerized; blood flow, tissue plasma, and lymph are increased. Accumulated PMNs die and lyse, forming pus, from which DNA was first isolated during Crimean War.
Term
Eosinophils
Definition
Function to destroy larval parasites and in allergic reactions. 12-14 um in diameter with a bi or tri lobed nucleus. Only contain specific secondary granules, which are larger than those fo PMNs and stain orange-red. May have a crystalline band seen in TEM. Granules contain Major Basic Protein (MBP) and other anti-larval factors
Term
Destruction of Parasite larvae by Eosinophils
Definition
ie: ascariasis, trichinosis, or schistomosias. T cells, basophils, and mast cells release a factors such as histamine which are cemotactic for eosinophils. Bind to IgG or IgE antibodies, surround larvae, and degranulate all over them. MBP is toxic to these organisms.
Term
Modulation of inflammation response by Eosinophils
Definition
Eosinophils phagocytize Ag-Ab complexes, and atagonize inflammatory factors of mast cells and basophils, ie destroying histamine.
Term
Allergic Reactions
Definition
associated with high levels of eosinophils, especially those having to do with IgE. Many eosinophils found in airways affected by asthma, and may contribute to pathogy.
Term
Basophil
Definition

8-10 um in diameter with bilobed nucleus. Granules similar to mast cells, containing histamine and heparin. Histamine, SRS (slow reacting substance), and other molecules responsible for vasodilation. Rare in blood (5,000/ml)

 

Function like mast cells 1)In immunological stimuli by secreting cytokines and other singaling molecules besides histamine to recruite eosinophiles and lymphocytes. Make IL-4, which is important in the production of Th2 cells and antibody production.

2)May be involved in Delayed Type Hypersensitivity Reacitons, though T cell release of cytokines in response to stimulation may be responsible.

 

3)Immediate hypersensitivity produced by mast and basophils releasing factors in response to antigens binding to IgE

 

Term
Monocytes
Definition

Precursor of tissue macrophages. Largest blood cell at 12-20 um. Nucleus is kidney shaped, lacy chromatin. Cytoplasm is gray or blue, granules usually not visible, occasional vacuoles.

 

Function as precursor, phagocytosis of microbes and old or damaged host cells, participate in immune response (process antigen, remove excess antigen, present antigen to lymphocytes, secrete cytokines)

Term
Platelets
Definition

200/400 million/ml. Cell fragments 2 um. No nucleus, but do have organelles. Look like dirt on smears.

 

Function in hemostasis through endothelial cell maintenance (release factors that keep small blood vessels from leaking) and Clotting. Clotting causes platelets to bind to collagen and other ECM components via receptors, causing them to spread out and move. Other platelets bind to adhering platelets and a plug is formed. Plug interacts with clot and fibrinogen converted to fibrin by thrombin, resulting in successful clot. Later, platelets contract resulting in clot retracting through actin and myosin.

Term
Lymphocytes
Definition

Small cells size of RBCs. Contain dense nucleus and little cytoplasm, which is bluish when visible. Large lymphocytes can be distinguished from monocytes by appearance of nucleus and color (K, NK cells).

 

Function as main players in acquired immunity

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