Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
174 Cards in this Set
- Front
- Back
|
What 3 events directly trigger the first step of wound healing?
|
1. Cell death
2. Disruption/Denaturation of the extracellular matrix 3. Loss of the blood vessel |
|
|
What is the first phase of Wound Healing?
|
Blood Coagulation
|
|
|
What are the 3 major categories contained in Blood?
|
1. Buffy coat
2. Plasma 3. RBC |
|
|
What is Hematopoiesis?
|
A complex process that forms all blood cells
|
|
|
By adulthood, where is the blood-cell producing bone marrow typically found?
|
In cancellous bone like the ends of the humorus, tibia, femurs, pelvis, ribs and sternum.
|
|
|
What is the Stroma?
|
3D network of spongelike tissue found in marrow made up of cells and structural fibers.
|
|
|
Within the stroma, what two things are found?
|
1. sinuses (empty spaces)
2. Sinusoidal capillaries (provide blood supply for marrow) |
|
|
Blood cells are continually being formed where?
|
In the stroma of the bone marrow!
|
|
|
All of the cells that circulate in the bloodstreamare derived from what cell type?
|
Pluripotent hematopoietic stem cells!
|
|
|
What does Pluripotent cells mean?
|
Cells that can replicate and differentiate into multiple cell types.
|
|
|
What does Totipotent Cells mean?
|
Cells that can produce ANY other cell type
|
|
|
1 ounce of blood contains how many cells?
|
~260 Billion
|
|
|
PHSCs can replicate into more PHSCs or can differentiate into what two stem cell types?
|
1. Lymphoid stem cells
2. Myeloid stem cells |
|
|
Lymphoid stem cells migrate from the bone marrow to where? What do they form?
|
To the lymphatic system where they eventually produce lymphocytes
|
|
|
What are lymphocytes?
|
White blood cells of the lymphatic system
|
|
|
The myeloid stem cells remain where? What do they produce?
|
They remain in the bone marrow where they produce RBC, platelets, and leukocytes.
|
|
|
What is Plasma composed of?
|
Water, salts (sodium, potassium, calcium, magnesium, chloride, bicarbonate), and Proteins (albumin, fibrinogen, immunoglobulins)
|
|
|
Blast is used to denote what kind of cell?
|
PRECURSOR cell or a cell that has the capability to differentiate into another cell type
|
|
|
What does Reticulo refer to?
|
Having a network of filaments
|
|
|
At which stage in the formation of RBCs does mitosis no longer occur? What happens instead?
|
Orthochromatic erythroblast stage where the nucleus is expelled from the cell during the process of the cell squeezing into a sinusoidal capillary from the stroma)
|
|
|
From an Myeloid Stem Cell, list the 5 precursor cells of an Erythrocyte?
|
1. Proerythroblast
2. Basophil erythroblast 3. Polychromatophil erythroblast 4. Orthochromatic Erythroblast 5. Reticulocyte ERYTHROCYTE |
|
|
Reticulocytes contain a small amount of what?
|
Residual nuclear fragments - the filaments for which the cells are named
|
|
|
Within a few days, what happens to the remaining nuclear fragments, cytoplasmic mitochondria, ribosomes, and other enzymes in reticulocytes?
|
They are denatured and the reticulocyte is now a mature Erythrocyte
|
|
|
Why do erythrocytes not proliferate or synthesize hemoglobin?
|
Because they have no nucleus or cytoplasmic organelles needed for protein synthesis
|
|
|
RBCs function purely as a mechanism for what?
|
Transport mechanism for oxygen and carbon dioxide
|
|
|
How long do human erythrocytes survive in the circulation? What happens?
|
120 days until they are removed by macrophages
|
|
|
In order to meet the oxygen demands of the body, what two things are occurring?
|
1. RBC generation is always occurring
2. Can be upregulated in response to increased oxygen demand |
|
|
Where is Erythropoitin mainly formed?
|
In the kidneys!
|
|
|
Erythropoitin stimulates the production of what?
|
Proerythrocytes from hemapoietic stem cells in the bone marrow!
|
|
|
Platelets originate in the bone marrow via what?
|
Via the fragmentation of larger megakaryocytes
|
|
|
As megakaryocytes mature, what happens?
|
Membrane invaginates and develops a network throughout the cytoplasm called demarcation membranes.
|
|
|
What happens to Demarcation Membranes?
|
The megakaryocyte fractures along these membranes when they squeeze through the marrow vasculature. These fractures are platelets.
|
|
|
What is the half-life of Platelets?
|
8 to 10 days
|
|
|
How are inactive platelets cleaned out?
|
Cleaned out by the spleen by macrophage scavenger cells.
|
|
|
What is a prominent feature of Platelets?
|
They contain granules
|
|
|
What do Granules contain?
|
A variety of chemicals that are important to the process of coagulation.
|
|
|
Platelets contain what contraction proteins?
|
Actin, myosin, and thrombosthenin
|
|
|
What allows a platelet to be a functionally active unit?
|
The residual megakaryocyte ER, Golgi apparatus, and mitochondria give it a short-term supply of enzymes, ATP, and calcium.
|
|
|
Platelet membranes contain what two things? Why?
|
Glycoproteins and specialized adhesion receptors for cellular adhesion to damaged endothelial cells!
|
|
|
What is Arginine-Glycine-Aspartic Acid?
|
Amino acid sequence that is part of the AA sequence of collagen which the specialized adhesion receptors on platelets interact with!
|
|
|
Simply, what is Collagen?
|
A protein in the basement membrane that normally is covered by an endothelial layer
|
|
|
Simply, when the endothelium is injured or compromised, what happens in terms of collagen and platelets?
|
Collagen is exposed to the bloodstreem and platelets come and adhere to the collagen via their membrane receptors.
|
|
|
What is von Willebrand factor?
|
Protein found in the blood that binds to collagen with high affinity which platelets then bind to the vW factor.
|
|
|
Once a platelet adheres to a surface, what happens?
|
Contractile proteins within the platelets tighten, the platelet flattens and forms pseudopodia
|
|
|
The contraction of proteins in the platelets cause what to happen?
|
Causes the platelets to degranulate
|
|
|
What is Degranulation?
|
The release of ADP and thromboxane A2 from the granules in platelets when they contract.
|
|
|
What are ADP and Thromboxane A2?
|
Potent platelet activators signalling other platelets for recruitment and injury site.
|
|
|
What is a major end product of coagulation?
|
The production of fibrin
|
|
|
What is Fibrin?
|
Protein whose threads attach to and help consolidate the platelet plug as well as trap RBC
|
|
|
What are the 2 important general mechanisms by which chemicals released from aggregating platelets assist in the formation of a blood clot?
|
1. Arachidonic Acid cascade
2. Thrombin Mechanism |
|
|
TRUE OR FALSE: The Arachidonic Acid Cascade can promote and inhibit platelet aggregation.
|
TRUE
|
|
|
What stimulates the Arachidonic Acid Cascade?
|
By the presence of chemicals released from other platelets
|
|
|
What is a key control point in the arachidonic acid cascade?
|
Cyclooxygenase!
|
|
|
Factor V can be released by platelets and is activated by what?
|
Thrombin!
|
|
|
Factor Va and Factor Xa combine to form what?
|
Prothrombin Activator!
|
|
|
What is Prothrombin Activator?
|
Activator that acts to split the plasma protein Prothrombin into fragments, generating more thrombin
|
|
|
What is Thrombin?
|
An enzyme that acts to cleave peptide fragments away from fibrinogen to produce fibrin monomers.
|
|
|
What do Fibrin Monomers do?
|
They polymerize with the help of the stabilizing factor VIII
|
|
|
What releases Stabilizing Factor VIII? What activates it? What does it form?
|
Platelets where it is then activated by thrombin to form polymerized fibrin threads
|
|
|
Fibrinogen is necessary for what?
|
For the adhesion of platelets to other platelets and subsequent aggregation.
|
|
|
What are the 3 main things that Thrombin does?
|
1. Increases platelet-platelet adhesion
2. Stimulates platelet activation 3. Degranulation - which creates more thrombin! |
|
|
What is Vascular Spasm?
|
A constriction of blood vessels which stops or slows blood flow.
|
|
|
Coagulation is a result of what?
|
A result of cascading chemical reactions of plasma proteins (clotting factors)
|
|
|
What is the Extrinsic Pathway?
|
A coagulation cascade that begins with trauma to vascular walls and surrounding tissues.
|
|
|
Tissue trauma causes the release of what 3 things?
|
Tissue Thromboplastin, phospholipids from damaged cell membranes, and lipoprotein complex.
|
|
|
The lipoprotein complex can function as what kind of enzyme?
|
A proteolytic (protein digesting) enzyme
|
|
|
Tissue thromboplastin combines with and activates what? What does this activate?
|
Combines with and activates Factor VII. This complex then activates Factor X.
|
|
|
Factor Xa combines with phospholipids from what?
|
Tissue thromboplastin or platelets
|
|
|
Factor Xa combines with phospholipids and Factor Va to form what?
|
Prothrombin activator!
|
|
|
What is the Intrinsic Pathway?
|
Coagulation cascade that begins with the exposure of blood to a foreign surface or with trauma to platelets within the blood
|
|
|
TRUE OR FALSE: Blood coagulation is not automatically initiated upon the implantation of a biomaterial or device.
|
FALSE. It IS automatically initiated!
|
|
|
TRUE OR FALSE: No biomaterial is inert, to date.
|
TRUE! :(
|
|
|
To start the intrinsic cascade, what binds to the foreign surface?
|
Factor XII!
|
|
|
Platelets that adhere to the foreign surface or are damage release what 2 things in the intrinsic pathway?
|
1. phospholipids
2. platelet factor 3 |
|
|
The intrinsic and extrinsic pathways join at the activation of what? What do they culminate with?
|
Factor X and culminate in the same thrombin-mediated mechanisms
|
|
|
What is the Common Pathway?
|
The mutual pathways in the Intrinsic and Extrinsic pathways that are the series of reactions from factor X to the formation of fibrin
|
|
|
In the Intrinsic Pathway, what two compounds bind to the surface?
|
1. High molecular weight Kininogen (HMWK)
2. Factor XII |
|
|
What 2 things circulate in the blood bound to HMWK? What happens?
|
1. Factor XI
2. Prekallikrein So when HMWK adsorbs to the surface, prekallikrein and Factor XI are in close proximity to the adsorbed Factor XII |
|
|
Factor XIIa can convert what into what?
|
Prekallikrein to Kallikrein
|
|
|
Once activated, Kallikrein can then activate what?
|
Factor XII that was not activated when it adsorbed into the surface.
|
|
|
Once the prekallikrein has been converted to kallikrein, the HMWK-Kallikrein complex can do what?
|
Can desorb from the surface!
|
|
|
Active Kallikrein can enzymatically cleave what?
|
Small polypeptides called Kinins from circulating serum proteins.
|
|
|
What is the purpose of Kinins?
|
Cause vasodilation and increase vascular permeability which is important to inflammation!
|
|
|
Kinins can stimulate what two things?
|
1. pain receptors
2. smooth muscle contraction which aids the vascular spasm response |
|
|
How important is Calcium in the coagulation cascade?
|
Calcium is required for all reactions in the cascade except for the activation of Factors XII and XI.
|
|
|
What happens if Calcium is not present during the coagulation cascade?
|
Blood will not clot!
|
|
|
What is one way to keep blood from coagulating outside the body?
|
Addition of precipitating or chelating calcium (with EDTA)!
|
|
|
What are 4 control points in the coagulation cascade? (that is, if you mess with them, coagulation could potentially be stopped.)
|
1. Calcium
2. Thrombin 3. Platelet contributions 4. Clotting factors |
|
|
Deficiency in which Factor is the cause of hemophilia A?
|
Factor VIII
|
|
|
What is one nonspecific biological control mechanism that keeps coagulation in check?
|
The passing of blood volume dilutes coagulants and removes them from the local area of injury.
|
|
|
Activated blood clotting factors are removed from the circulation where?
|
The liver!
|
|
|
What helps keep coagulation localized?
|
The membranes of activated platelets help keep the coagulation reactions localized to the site of injury
|
|
|
What keeps coagulation from occurring on healthy endothelium?
|
The smooth glycocalyx mucopolysaccharide layer!
|
|
|
What is the name of the endothelial membrane protein that binds to thrombin and thus prevents the coagulation cascade from furthering?
|
Thrombomodulin!
|
|
|
Thrombomodulin-Thrombin complex can activate vitamin K dependent plasma protein C which inactivates which factors?
|
Factors Va and VIIIa
|
|
|
Protein S inactivates what?
|
Factors Va and VIIIa
|
|
|
Deficiencies of protein C or S can lead to what?
|
Excessive clotting and the formation of blood clots
|
|
|
What is one of the most powerful naturally occuring anticoagulants?
|
Fibrin!
|
|
|
Approximately 85-90% of the thrombin formed during coagulation does what?
|
Adsorbs to the newly polymerized fibrin threads
|
|
|
What is Antithrombin III?
|
A serum protein that binds and inactivates much of the non-adsorbed thrombin within 20 minutes.
|
|
|
What is Heparin?
|
A polysaccaride that has little to no anticoagulant activity on its own
|
|
|
In order to increase its effectiveness at removing thrombin from the blood, antithrombin III is complexed with what?
|
Heparin!
|
|
|
The Heparin-ATIII complex also inactivates what factors?
|
IXa, Xa, XIa, and XIIa
|
|
|
Of the Heparin-ATIII complex, which is usually the limiting factor?
|
Heparin!
|
|
|
Are blood clots passively or actively removed?
|
Actively removed within 24 to 48 hours!
|
|
|
During coagulation, what plasma protein is trapped in the forming clot?
|
Plasminogen
|
|
|
Injured tissues release a complex called what which over 1-2 days converts plasminogen into plasmin?
|
Tissue Plasminogen Activator!
|
|
|
What is Plasmin?
|
A proteolytic enzyme similar to trypsin that digests the fibrin threads of a clot, fibrinogen, prothrombin, and factors V, VIII, and XII.
|
|
|
What inactivates Plasmin?
|
Serum protein alpha2-antiplasmin
|
|
|
At a coagulation site, the local amount of plasmin has to do what to be an effective fibrinolytic (fibrin destroying) agent?
|
It must rise above a critical level suppressible by passing alpha2-antiplasmin
|
|
|
What is Intima Hyperplasia?
|
Overgrowth of the intimal tissue near or on a device
|
|
|
What are three major clinical challenges that need to be solved due to thrombosis and other issues with biomaterials and implants?
|
1. Vascular grafts
2. Blood oxygenators 3. Heart valves |
|
|
What are the 3 main mechanisms of vascular autograft failure?
|
1. thrombosis
2. emboli production 3. intimal hyperplasia |
|
|
What are Anastomotic sites?
|
The sites where the graft was sutured into the original blood vessel
|
|
|
What is the issue with Anastomotic sites?
|
May be focal points for increased mechanical strain on the surrounding tissues which can contribute to intimal hyperplasia
|
|
|
What is knitted Dacron?
|
A popular synthetic vascular graft material used for medium and large diameter graft sites
|
|
|
What is typically done to Dacron before implantation?
|
It may be exposed to a patient's blood to allow "preclotting" to prevent excessive blood leakage through the fabric
|
|
|
What is another popular synthetic vascular graft material besides Dacron?
|
Expanded poly(tetrafluoroethylene) which shows low incidences of thrombosis or hyperplasia as long as diameter is > 4mm
|
|
|
Why is smaller diameter vascular grafts not currently possible?
|
Prolonged blood-biomaterial contact due to reduced blood flow or relatively high surface to volume ratio of these grafts which may increase coagulation activation
|
|
|
What are the 2 main types of blood oxygenators in use?
|
1. Bubble oxygenators
2. Membrane oxygenators |
|
|
What are Bubble oxygenators?
|
oxygen gas is mixed directly with the blood
|
|
|
What are membrane oxygenators?
|
Oxygen diffuses across a membrane for uptake by RBC
|
|
|
What is an issue with Bubble Oxygenators?
|
Blood cell trauma due to air-liquid interfaces
|
|
|
What is an issue with Membrane Oxygenators?
|
Hemolysis, platelet loss, and circulating coagulation factor depletion occur!
|
|
|
Heart valves made from synthetic materials typically utilize what?
|
A caged ball or tilting disk to periodically permit blood flow
|
|
|
What are allografts?
|
A transplant from a member of the same species
|
|
|
What are some issues with xenografts of heart valves?
|
Tissue must be chemically treated with glutaraldehyde so the patient doen't have an immune response
|
|
|
What is a problem with glutaraldehyde used to reduce the potential for an immune response to xenografted heart valves?
|
It chemically cross-links the collagen in the tissues which stiffen the tissue leaflets and therefore change the mechanical properties
|
|
|
What are 4 important facts about the ECM?
|
1. Multifunctional
2. Acts as support, reservoir, + modulator for bioactive molecs. like GF 3. Dynamic meshwork 4. Mechanical/Biophysical role to support + maintain tissue/organ structure |
|
|
Blood coagulation occurs within how much time?
|
1-2 minutes
|
|
|
Inflammation occurs within how much time?
|
Within a few hours
|
|
|
Proliferation occurs within how much time?
|
Within a few days
|
|
|
Remodeling can last for how long?
|
Up to a year!
|
|
|
How large are platelets?
|
2-3 micrometer disks
|
|
|
TRUE OR FALSE: Megakaryocytes leave the hemapoitic island.
|
FALSE. They stay in the hemapoitic island
|
|
|
What 5 things activate Platelets?
|
1. Epinephrine
2. Serotonin 3. ADP 4. Thrombin 5. Collagen |
|
|
After how much time are platelets permanently fused?
|
~2 minutes
|
|
|
Advil/Aspirin blocks what cycle?
|
Cyclo-oxygenase cycle!
|
|
|
List the 5 step sequence to Platelet Activation
|
1. Exposure to activators
2. change in morphology (internal and external) 3. Adhesion to substrates - fingerlike projections 4. Aggregation 5. Formation of platelet plug |
|
|
What are the 2 Arachidonic Acid Metabolites?
|
1. Prostaglandins
2. Leukotrienes |
|
|
What are the 3 main systems of Plasma Proteases important in Inflammation?
|
1. Kinin system
2. Complement system 3. Coagulation/fibrinolytic system |
|
|
What are 8 important chemical mediators of Inflammation derived from Plasma, Cells, and Injured Tissue?
|
1. Vasoactive amines
2. Plasma proteases 3. Arachidonic acid metabolites 4. Lysosomal proteases 5. Oxygen-derived free radicals 6. Platelet activating factors 7. Cytokines 8. Growth Factors |
|
|
What are the 5 main classes of Immunoglobulin?
|
1. IgG
2. IgA 3. IgM 4. IgE 5. IgD |
|
|
Which immunoglobulin is the only one to cross the placenta to circulate through the fetal blood stream?
|
IgG
|
|
|
What is the main function of IgA?
|
Provide protection against the proliferation of microorganisms in bodily secretions.
|
|
|
What are 2 important facts about IgM?
|
1. One of two major immunoglobulins expressed on B lymphocytes
2. Effective complement system activator |
|
|
Which immunoglobulin has a high affinity for membrane receptors on basophils and mast cells?
|
IgE
|
|
|
Which of the immunoglobulins are expressed on B lymphocytes?
|
IgM and IgD
|
|
|
What is the purpose of the Complement C1?
|
Stabilization of immune complexes
|
|
|
What is the purpose of the Complement C2?
|
Vasodilation and increased vascular permeability caused by C2 Kinin
|
|
|
What is the purpose of the Complement C3?
|
C3a - anaphylatoxin and chemotaxis
C3b - immune adherence (opsonization and Lymphocyte activation |
|
|
What is the purpose of the Complement C4?
|
C4a - anaphylatoxin
C4b - Virus neutralization |
|
|
What is the purpose of the Complement C5?
|
C5a - anaphylatoxin and chemotaxis
|
|
|
What is the purpose of the Complements C5b, 6, and 7?
|
Chemotaxis!
|
|
|
What is Fibrinolysis?
|
Fibrin and Fibrinogen degradation products inhibit the polymerization of fibrin monomers during the conversion of fibrinogen into fibrin clots.
|
|
|
Which Fibrinogen Degradation Products are particularly effective inhibitors? What may they be responsible for?
|
X and Y may be responsible for a prolonged clotting time in a coagulation assay
|
|
|
In Fibrinolysis, fibrin is degraded by what?
|
Plasmin
|
|
|
How does Plasmin degrade fibrin?
|
This proteolytic enzyme splits insoluble fibrin into soluble fibrin degradation products.
|
|
|
What are 3 important facts about Thrombin?
|
1. Potent aggregation inducer
2. Potent release inducer 3. Initiates clot retraction |
|
|
What facilitates platelet aggregation?
|
Fibrinogen!
|
|
|
Which factor is some how involved in the interaction between platelets and the vessel wall?
|
Factor VIII
|
|
|
Where does Heparin originate?
|
From mast cells in the intestinal mucosa and other tissues
|
|
|
What is the Heparin Cofactor?
|
Antithrombin III
|
|
|
By itself, is Anti-Thrombin III fast or slow?
|
SLOOOOW
|
|
|
What is the purpose of Albumin?
|
Maintain blood equilibrium
|
|
|
What is the most abundant protein found in the blood?
|
Albumin!
|
|
|
From a pluripotent stem cell, list the 3 steps to Platelets.
|
1. Megakaryoblast
2. Promegakaryocyte 3. Megakaryocyte PLATELET |
|
|
A plasma cell comes from what?
|
Nonleukemic lymphoblast
|
|
|
What are the 10 subcellular structures of a Platelet?
|
1. Fuzzy coat
2. Plasma membrane 3. Submembraneous area 4. Microtubuli 5. Alpha-granules 6. dense bodies 7. Glycogen particles 8. mitochondria 9. dense tubular system 10. surface-connecting tubules |
|
|
What are Alpha Granules?
|
Granules found in platelets that contain lysozomal enzymes, fibrinogen, glycosamino-glycans
|
|
|
What keep the platelets disk shaped?
|
Microtubuli
|
|
|
What is the fuzzy coat of Platelets?
|
Layer of glycoproteins and acid mucopoly-saccharides
|
|
|
What are Dense Bodies?
|
Found in platelets, they contain serotonin, ADP and ATP and Ca2+
|
|
|
What are Surface-Connecting Tubules?
|
Found in Platelets, they connect with extracellular medium and are the secretory channels for the contents of granules
|
