node1 node2 inter1 inter2 node3 inter3 inter4 node5 node4 inter6 inter5 site1 site2 site7 site8 site4 site3 site6 site5 ExitProgram FirstPage 1st Page THE END Basic Questions This section contains 20 questions based on the information in the previous pages which will take about 10 minutes to complete. Once in the quiz it is only possible to go forwards - it is not possible to exit or return to previous pages.us pages GOOD LUCK! backPage Previous default buttonUp buttonUp Previous default NextPage default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page 4questscore19 4questscore20 B"19a" B"19b" B"19c" B"19d" B"19e" B"20a" B"20b" B"20c" B"20d" B"20e" 4questscore18 4questscore17 4questscore16 4questscore15 4questscore14 4questscore13 4questscore12 4questscore11 4questscore10 4questscore9 4questscore8 4questscore7 4questscore6 4questscore5 4questscore4 4questscore3 --System count questscores --Obtain dialog box showing total no points "You scored" && out a possible 100" --shows nextpage B- avoids Bbeing pressed without --obtaining B"NextPage" default buttonUp buttonUp You scored points out of a possible 100 NextPage default count questscore1 questscore2 questscore3 questscore4 questscore5 questscore6 questscore7 questscore8 questscore9 questscore10 questscore11 questscore12 questscore13 questscore14 questscore15 questscore16 questscore17 questscore18 questscore20 questscore19 "fib1" 0, 75.125, 100 "fib2" 0, 75.125, 100 "fib3" 240, 75.125, 100 "fib4" 240, 75.125, 100 0, 87.625, 100 0, 87.625, 100 240, 87.625, 100 240, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 "site1" 0, 75.125, 100 "site2" 240, 75.125, 100 "site7" 0, 75.125, 100 "site8" 240, 75.125, 100 0, 87.625, 100 240, 87.625, 100 "site3" 0, 87.625, 100 "site4" 0, 87.625, 100 "site5" 240, 87.625, 100 "site6" 240, 87.625, 100 0, 87.625, 100 240, 87.625, 100 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 "node1" 0, 75.6875, 0 "node2" 0, 75.6875, 0 "node3" 0, 75.6875, 0 "node4" 0, 75.6875, 0 "node5" 0, 75.6875, 0 "arm1" 0, 75.6875, 0 "arm2" 0, 75.6875, 0 "inter1" 0, 75.6875, 0 "inter2" 0, 75.6875, 0 "inter3" 0, 75.6875, 0 "inter4" 0, 75.6875, 0 "inter5" 0, 75.6875, 0 "inter6" 0, 75.6875, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 buttonUp buttonUp site1 site2 site7 site8 site1 site2 site3 site4 site5 site6 site7 site8 site1 site2 site3 site4 site5 site6 site7 site8 site1 site2 site3 site4 site5 site6 site7 site8 site1 site2 site3 site4 site5 site6 site7 site8 node1 node2 node3 node4 node5 inter1 inter2 inter3 inter4 inter5 inter6 node1 node2 node3 node4 node5 inter1 inter2 inter3 inter4 inter5 inter6 node1 node2 node3 node4 node5 inter1 inter2 inter3 inter4 inter5 inter6 node1 node2 node3 node4 node5 node1 node2 node3 node4 node5 node1 node2 node3 node4 node5 inter1 inter2 inter3 inter4 inter5 inter6 "Really quit?"\ f"Yes" "fib1" 0, 75.125, 100 "fib2" 0, 75.125, 100 "fib3" 240, 75.125, 100 "fib4" 240, 75.125, 100 0, 87.625, 100 0, 87.625, 100 240, 87.625, 100 240, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 "site1" 0, 75.125, 100 "site2" 240, 75.125, 100 "site7" 0, 75.125, 100 "site8" 240, 75.125, 100 0, 87.625, 100 240, 87.625, 100 "site3" 0, 87.625, 100 "site4" 0, 87.625, 100 "site5" 240, 87.625, 100 "site6" 240, 87.625, 100 0, 87.625, 100 240, 87.625, 100 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 "node1" 0, 75.6875, 0 "node2" 0, 75.6875, 0 "node3" 0, 75.6875, 0 "node4" 0, 75.6875, 0 "node5" 0, 75.6875, 0 "arm1" 0, 75.6875, 0 "arm2" 0, 75.6875, 0 "inter1" 0, 75.6875, 0 "inter2" 0, 75.6875, 0 "inter3" 0, 75.6875, 0 "inter4" 0, 75.6875, 0 "inter5" 0, 75.6875, 0 "inter6" 0, 75.6875, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 0, 97.25, 0 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 60, 87.625, 100 SysSuspendMessages buttonUp buttonUp Really quit? site1 site2 site7 site8 site1 site2 site3 site4 site5 site6 site7 site8 site1 site2 site3 site4 site5 site6 site7 site8 site1 site2 site3 site4 site5 site6 site7 site8 site1 site2 site3 site4 site5 site6 site7 site8 node1 node2 node3 node4 node5 inter1 inter2 inter3 inter4 inter5 inter6 node1 node2 node3 node4 node5 inter1 inter2 inter3 inter4 inter5 inter6 node1 node2 node3 node4 node5 inter1 inter2 inter3 inter4 inter5 inter6 node1 node2 node3 node4 node5 node1 node2 node3 node4 node5 node1 node2 node3 node4 node5 inter1 inter2 inter3 inter4 inter5 inter6 "quest11" "quest12" leavePage leavePage quest11 quest12 Factor Xa ::: Has clusters of negative charges Binds directly to aggregated platelet surface Converts fibrinogen into fibrin Converts prothrombin into thrombin Activates fibrinoligaseee Which of the following are proteolytic enzymes : Thrombin Fibrinoligase Factor Va Factor Xa Factor X glutamate residues on the surface g-carboxyglutamate residues on the surface Glutamate & aspartate residues on the surface Clusters of different negative residues on the quest11 quest12 NextPage 4questscore11 4questscore12 B"11a" B"11b" B"11c" B"11d" B"11e" B"12a" B"12b" B"12c" B"12d" B"12e" default buttonUp buttonUp default questscore12 questscore11 "quest13" "quest14" leavePage leavePage quest13 quest14 Platelets normally have contact with : Red blood cells Other platelets Luminal surface of endothelial cells Collagen Plasma The conversion of prothrombin to thrombin on an aggregated platelet surface: Takes place at a faster rate than in solution Serves to localize blood coagulation to damage site Takes place at a slower rate than in solution Takes place at a similar rate to that in solution Requires the presence of calcium ions t damage site site NextPage 4questscore13 4questscore14 B"13a" B"13b" B"13c" B"13d" B"13e" B"14a" B"14b" B"14c" B"14d" B"14e" default buttonUp buttonUp default questscore14 questscore13 quest13 quest14 "quest15" "quest16" leavePage leavePage quest15 quest16 Phosphatidyl serine : Is negatively charged Is present on outer surface of platelet plasma membrane Is present on outer surface of aggregated platelet plasma membrane Is present on outer surface of platelet vesicle membrane Is present on inner surface of platelet vesicle membrane Some characteristics of the blood coagulation system are : It includes a series of protein-proteinase activations Is an example of a biochemical amplifier Results in the formation of fibrin Is localised to the damage site by platelet aggregation Requires calcium ions to proceedons to proceedium ions to proceed NextPage )4T_ 4questscore15 4questscore16 B"15a" B"15b" B"15c" B"15d" B"15e" B"16a" B"16b" B"16c" B"16d" B"16e" default buttonUp buttonUp default questscore16 questscore15 quest15 quest16 4quest "quest17" "quest18" leavePage leavePage quest17 quest18 Individual fibrin monomers within hard clots are : Cross-linked together by disulphide bonds Cross-linked together by peptide bonds Cross-linked together by isopeptide bonds Cross-linked together by g-glutamyl,e-lysine links Held together by links involving g-carboxylglutamate The formation of a 3-D fibrin mesh occurs as a result of : Release of fibrinopeptide B from protofibrils Release of fibrinopeptide B from fibrinogen Release of fibrinopeptide A from protofibrils Release of fibrinopeptide A from fibrinogen Action of fibrinoligase NextPage 4questscore17 4questscore18 B"17a" B"17b" B"17c" B"17d" B"17e" B"18a" B"18b" B"18c" B"18d" B"18e" default buttonUp buttonUp default questscore18 questscore17 quest17 quest18 cj j j 6 B"NextPage" "quest19" "quest20" enterPage leavePage enterPage NextPage leavePage quest19 quest20 Percentage of fibrinogen mass lost on conversion to fibrin is approx :ox : Fibrinogen is soluble because ::::::::::::::::::::::::::: It is trinodular It has fibrinopeptide A and B regions It has not been cross-linked It no glutamate residues It has lost fibrinopeptide A NextPage 4questscore19 4questscore20 default buttonUp buttonUp default questscore20 questscore19 quest19 quest20 buttondown buttondown Score Press the 'Score' button after finshing the questions to obtain your final score. "bond1" "bond2" "bond3" "bond4" "bond5" "The covalent links formed between adjacent fibrin monomers create extensive covalently-linked network structure." "ligase" )-2310, 1515 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 H307.5, 0 "REPEAT OR MOVE ON TO THE NEXT PAGE" default buttonUp buttonUp words bond1 bond2 bond3 bond4 bond5 The covalent links formed between adjacent fibrin monomers create an extensive covalently-linked network structure. words ligase bond1 bond2 bond3 bond4 bond5 REPEAT OR MOVE ON TO THE NEXT PAGE words default ligase Basic Answers to Haemostasis Questions The answers to the problems that you got wrong can be seen below. Once you have read the correct answer click the mouse in the white box to move onto the next answer. NextPage default buttonUp buttonUp default answer20 "answer20" buttonUp buttonUp answer20 Question 20: Both fibrinopeptides A and B carry significant charge which makes them hydrophilic and their presence mask binding sites that allow polymerization of fibrin monomersfibrinopeptide A.to the repressor site and CAP site respectively.to the DNA. answer19 "answer19" buttonUp buttonUp answer19 Question 19: The molecular mass of fibrinogen is 340,000. The mass of a single fibrinopeptide is approximately 2000. The four fibrinopeptides consitute approximately 2% of the total mass of fibrinogen.. is the mass of the four fibrinopeptides. answer18 "answer18" buttonUp buttonUp answer18 Question 18: The release of fibrinopeptide A only allows the formation of protofibrils. Release of fibrinopeptide B from the protofibrils allows them to aggregate side-to-side and form a 3-D network... answer17 "answer17" buttonUp buttonUp answer17 Question 17: The fibrin monomers within a hard clot are cross-linked together by isopeptide bonds. These covalent bonds are between the g-carbonyl group of the glutamine and the e-amino group of lysine. answer16 "answer16" buttonUp buttonUp answer16 Question 16: The blood coagulation system includes a series of protein-proteinase activations. This cascade is a biochemical amplifier which results in the formation of a fibrin mesh. Localization of the coagulation system to the damaged site is achieved by platelet aggregation and requires calcium ions. answer15 "answer15" buttonUp buttonUp answer15 Question 15: Phosphatidyl serine is a negatively charged phospholipid that is found on the inner surface of the platelet vesicle membranes. When the vesicles fuse with the platelet plasma membrane the phosphatidyl serine is incorporated into the outer surface of the plasma membrane. answer14 "answer14" buttonUp buttonUp answer14 Question 14: The conversion of prothrombin to thrombin on the aggregated platelet surface takes place at a faster rate than in solution due to the localization mechanism. High concentrations of both factor Xa and prothrombin are generated on the aggregated platelet plasma membrane leading to a rate hundreds of times faster than in solution. answer13 "answer13" buttonUp buttonUp answer13 Question 13: Platelets circulate in the blood stream and as such have contact with red blood cells, other platelets, the luminal surface of the endothelial cells and plasma. Platelets only come into contact with collagen when the blood vessel is damaged. answer12 "answer12" buttonUp buttonUp answer12 Question 12: Thrombin and factor Xa are proteolytic enzymes. Factor X is the zymogen of factor Xa and as such has no proteolytic activity. Factor Va is accessory factor which enhances the activity of factor Xa. Fibrinoligase is a transamidase - it breaks one amide bond to form another. answer11 "answer11" buttonUp buttonUp answer11 Question 11: Factor Xa has clusters of negatively charged g-carboxygutamate residues on its surface. It binds to the aggregated platelet surface via calcium ions. It is a proteolytic enzyme which converts prothrombin into thrombin.... answer10 "answer10" buttonUp buttonUp answer10 Question 10: Platelets have vesicles containing 5-hydroxtryptamine, a vasoconstrictor. These vesicles have negatively charged phosopholipids on their inner surface so on fusing with the platelet plasma membrane the negative charges are transferred to the outer surface of the plasma membrane. polymerase or by forming a bend in the DNA.by forming a bend in the DNA. answer9 "answer9" buttonUp buttonUp answer9 Question 9: Fibrin no longer has the fibrinopeptides A and B so it contains 2a chains, 2b chains and 2g chains. sor also increases the affinity of RNA polymerase for the promoter by 100 fold. The result of this is that when lactose enters the cell the RNA polymerase is ready to start transcription immediately, leading to very quick production of the proteins. answer8 "answer8" buttonUp buttonUp answer8 Question 8: Fibrinogen contains 2a(A) chains, 2b(B) chains and 2g chains.nsation rises. Glucose concentration has no effect on the lactose concentration or the allolactose concentration. on or the allolactose concentration. enters the cell the RNA polymerase is ready to start transcription immediately, leading to very quick production of the proteins. answer7 "answer7" buttonUp buttonUp answer7 Question 7: Haemostasis is the process that prevents blood loss. Minor damage may be rectified by the aggregation of platelets alone. Major damage is repaired by platelet aggregation and the triggering of the coagulation system......eading to low lactose uptake into the cell. is made so only a small amount of lactose enters the cell. uction of the proteins. answer6 "answer6" buttonUp buttonUp answer6 Question 6: Protofibrils are are polymers of fibrinogen from which fibrinopeptide A has been released. The cleavage of fibrinopeptide A unmasks sites that allow the polymerisation to occur. polymerisation to occur. amount of permease is made so only a small amount of lactose enters the cell. ion immediately, leading to very quick production of the proteins. answer5 "answer5" buttonUp buttonUp answer5 Question 5: Aggregated platelets bind calcium ions to which prothrombin and factor Xa bind. Factor Va, which enhances the activity of factor Xa, also associates with aggregated platelets. This system localises haemostasis to the site of injury. only a small amount of lactose enters the cell. ion immediately, leading to very quick production of the proteins. answer4 "answer4" buttonUp buttonUp answer4 Question 4: Fibrinoligase forms isopeptide bonds linking the e-amino group of the lysine to the g-carbonyl group of the glutamine. Ammonia is released in the process. galactose. f lactose because only a small amount of permease is made so only a small amount of lactose enters the cell. ion immediately, leading to very quick production of the proteins. answer3 "answer3" buttonUp buttonUp answer3 Question 3: Platelets will adhere to collagen, which is only exposed at a damaged site. It also adheres to aggregated platelets, forming a plug which can stop minor bleeding...... ry of lactose because only a small amount of permease is made so only a small amount of lactose enters the cell. ion immediately, leading to very quick production of the proteins. answer2 "answer2" buttonUp buttonUp answer2 Question 2: Thrombin cleaves both fibrinopeptide A and B. It also activates the enzyme Fibrinoligase.......AP-cAMP complex, increasing the efficiency with which the enzyme can bind to the promoter. nly a small amount of permease is made so only a small amount of lactose enters the cell. ion immediately, leading to very quick production of the proteins. answer1 "answer1" buttonUp buttonUp answer1 Question 1: A typical turnover number for a proteolytic enzyme is 10 molecules of substrate per second... transacetylase - i.e those that control the entry and metabolism of lactose. ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page B"NextPage" 4questscore20 4questscore19 4questscore18 4questscore17 4questscore16 4questscore15 4questscore14 4questscore13 4questscore12 4questscore11 4questscore10 4questscore9 4questscore8 4questscore7 4questscore6 4questscore5 4questscore4 4questscore3 4count -- If the a question < 5, i.e got something wrong, -- answer that shown. "answer1" "answer2" "answer3" "answer4" "answer5" "answer6" "answer7" "answer8" "answer9" "answer10" "answer11" "answer12" "answer13" "answer14" "answer15" "answer16" "answer17" "answer18" "answer19" "answer20" enterPage leavePage enterPage NextPage answer1 answer1 answer2 answer2 answer3 answer3 answer4 answer4 answer5 answer5 answer6 answer6 answer7 answer7 answer8 answer8 answer9 answer9 answer10 answer10 answer11 answer11 answer12 answer12 answer13 answer13 answer14 answer14 answer15 answer15 answer16 answer16 answer17 answer17 answer18 answer18 answer19 answer19 answer20 answer20 NextPage count questscore1 questscore2 questscore3 questscore4 questscore5 questscore6 questscore7 questscore8 questscore9 questscore10 questscore11 questscore12 questscore13 questscore14 questscore15 questscore16 questscore17 questscore18 questscore19 questscore20 leavePage answer1 answer2 answer3 answer4 answer5 answer6 answer7 answer8 answer9 answer10 answer11 answer12 answer13 answer14 answer15 answer16 answer17 answer18 answer19 answer20 count questscore1 questscore2 questscore3 questscore4 questscore5 questscore6 questscore7 questscore8 questscore9 questscore10 questscore11 questscore12 questscore13 questscore14 questscore15 questscore16 questscore17 questscore18 questscore19 questscore20 BIBLIOGRAPHY D. Voet & J.G Voet - BIOCHEMISTRY (1990) Pages 1087 - 109555555555555 J. Hywel Thomas & B. Gillham - WILL'S BIOCHEMICAL BASIS OF MEDICINE - 2nd Edition, Pages 303-320 L. Stryer - BIOCHEMISTRY - 3rd Edition Pages 248-258 backPage Previous default buttonUp buttonUp Previous default NextPage default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page backPage Previous default buttonUp buttonUp Previous default NextPage default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page Animate5 Animate words EPEAT OR MOVE ON TO THE NEXT PAGEns to the second bundle at one end and the third bundle at the other end to form a mesh system. leavePage leavePage words backPage Previous default buttonUp buttonUp Previous default NextPage ID 33 default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page CONVERSION OF SOFT CLOT TO HARD CLOT: The fibrin network formed is a 'soft clot', so called because the interactions between the fibrin molecules are non-covalent (hydrophobic, van derWaals, electrostatic and hydrogen bonding). Thus the network can be dispersed by increasing the temperature to 45 degrees centigrade or by addition of hydrogen bond breakers eg urea . A 'hard clot' is one where the adjacent fibrin monomers are covalently cross-linked. These cross-links are isopeptide bonds between specific glutamine and lysine residues on neighbouring fibrin molecules. Isopeptide bonds are formed by the enzyme Fibrinoligase (factor XIIIa) which is activated by thrombin. rombin. ID 31 buttonUp buttonUp Thrombin Fibrinogen Fibrinogen Fibrinopeptides A + B Cross-linked Fibrin XIIIa (Fibrinoligase) "fib1" "fib2" "fib3" "fib4" "node1" "node2" "node3" "node4" "node5" "inter1" "inter2" "inter3" "inter4" "inter5" "inter6" "arm1" "arm2" "site1" "site2" "site3" "site4" "site5" "site6" "site7" "site8" 0, 50, 100 0, 50, 100 240, 50, 100 240, 50, 100 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 75.3125, 0 0, 50, 100 240, 50, 100 0, 75.125, 100 0, 75.125, 100 240, 75.125, 100 240, 75.125, 100 0, 50, 100 240, 50, 100 enterPage enterPage node1 node2 node3 node4 node5 inter1 inter2 inter3 inter4 inter5 inter6 site1 site2 site3 site4 site5 site6 site7 site8 node1 node2 node3 node4 node5 site1 site2 site3 site4 site5 site6 site7 site8 node1 node2 node3 node4 node5 inter1 inter2 inter3 inter4 inter5 inter6 site1 site2 site3 site4 site5 site6 site7 site8 CO - NH (CH ) - NH - CH - CO - - NH - CH - CO - | (CH ) | NH - NH - CH - CO - (CH ) NH CO (CH ) - NH - CH - CO - Lysine Glutamine FIBRINOLIGASE ID 30 buttonUp buttonUp -- p1b-p6b are platelets without vesicles. -- rp1, rp2, rp4 rbc's -- rp3 made up \(p1-p6) that will fill -- There 3 layers blood vessel - ' Kundamaged --'hole' einjured 'con' zconstricted "p1b" "p2b" "p3b" "p4b" "p5b" "p6b" "rp2" 2275, 300 "p1" )5095, 1155 "p2" )4315, 1140 "p3" )3385, 1155 "p4" )2890, 1065 "p5" )2350, 1095 "p6" )1885, 960 "rp3" "rp1" )3330, 2655 -1350, 2805 "rp4" -3840, 2685 "rp5" -285, 3090 "con" Put "" Normal The integrity endothelial cells intact so collagen surrounding does xcome contact contents H250, 0 H250, 0 H250, 0 H250, 0 H250, 0 H250, 0 H250, 0 H250, 0 H250, 0 H250, 0 When lining ruptured exposing H250, 0 H250, 0 H250, 0 H250, 0 H250, 0 H250, 0 "p1" 3800, 3870 "p2" H250, 0 "p3" H250, 0 "p4" H250, 0 "p5" H250, 0 "p6" H250, 0 fa section they adhere release 5-HT." H250, 0 H250, 0 H250, 0 "p1" 3850, 4170 "p2" H250, 0 "p3" H250, 0 "p4" H250, 0 "p5" H250, 0 "p6" H250, 0 H250, 0 H250, 0 H250, 0 "p2" H250, 0 "p3" H250, 0 "p4" H250, 0 "p5" H250, 0 "p6" H250, 0 H250, 0 H250, 0 H250, 0 "p2" H250, 0 "p3" H250, 0 "p4" H250, 0 "p5" H250, 0 "p6" H250, 0 H250, 0 H250, 0 H250, 0 "p2" 4130, 3870 "p3" H250, 0 "p4" H250, 0 "p5" H250, 0 "p6" H250, 0 H250, 0 H250, 0 H250, 0 "p2" 4220, 4170 "p3" H250, 0 "p4" H250, 0 "p5" H250, 0 "p6" H250, 0 H250, 0 H250, 0 H250, 0 "p3" H250, 0 "p4" H250, 0 "p5" H250, 0 "p6" H250, 0 H250, 0 H250, 0 H250, 0 "p3" H250, 0 "p4" H250, 0 "p5" H250, 0 "p6" H250, 0 H250, 0 H250, 0 H250, 0 "p3" 4545, 4245 "p4" H250, 0 "p5" H250, 0 "p6" H250, 0 "box" "screen" "ser1" "ser2" "ser3" "ser4" "ser5" 3330, 3180, 5115, 4350 2430, 2175, 5205, 4020 1545, 1350, 5310, 3675 -855, 315, 5445, 3465 3465, 1875 3420, 1830 )3525, 1935 "vac1" "rel1" )3270, 1125 4170, 1845 H0, -250 4185, 1845 H0, -250 H0, -250 4140, 1920 "vac2" "rel2" syLockScreen 4155, 1035 "drop1" 3210, 2160 3915, 795 3180, 2055 3555, 390 3165, 1995 4350, 1275 3240, 2310 "vac3" "rel3" H0, -250 4485, 2295 H0, -250 4545, 2175 H0, -250 4620, 2145 H0, -250 4470, 2325 "vac4" "rel4" 2910, 1380 4560, 1365 3885, 2370 4380, 1125 3885, 2220 4095, 825 3885, 2040 4005, 585 3840, 1845 3975, 390 3810, 1800 4740, 1560 3885, 2475 "vac5" "rel5" H0, -250 H0, -250 H0, -100 3885, 960 1545, 1350, 5310, 3675 2430, 2175, 5205, 4020 3330, 3180, 5115, 4350 -855, 315, 5445, 3465 Platelets bind other already laid down so can form a plug stop minor bleeding" H250, 0 H250, 0 H250, 0 "p4" H200, 100 "p5" H250, 0 "p6" H250, 0 H250, 0 H250, 0 H250, 0 "p4" 3985, 3975 "p5" H250, 0 "p6" H250, 0 H250, 0 H250, 0 H250, 0 "p5" H250, 0 "p6" H250, 0 H250, 0 H250, 0 H250, 0 "p5" H250, 0 "p6" H250, 0 3870, 315 H250, 0 H250, 0 "p5" 4265, 3735 "p6" H250, 0 H250, 0 H250, 0 "p5" 4385, 3960 "p6" H250, 0 H250, 0 H250, 0 "p6" 4495, 3570 H250, 0 H250, 0 "p6" 4645, 3915 5-HT released causes upstream injury site vasoconstrict so flow reduced." H250, 0 H250, 0 H250, 0 H250, 0 H250, 0 H250, 0 H250, 0 H250, 0 H250, 0 H250, 0 H250, 0 H250, 0 REPEAT OR MOVE ON TO THE NEXT PAGE" default buttonUp Z.buttonUp group vessel script Normal blood vessel - The integrity of the endothelial cells is intact so the collagen surrounding the blood vessel does not come into contact with the contents of the blood vessel. script When the endothelial cell lining is ruptured exposing the collagen to the contents of the blood vessel. script vessel Wungroup When platelets come into contact with a section of damaged blood vessel they adhere to the collagen and release the 5-HT. script screen screen screen screen screen drop1 drop1 screen screen screen screen screen Platelets bind to other platelets already laid down so they can form a plug that can stop minor bleeding script The 5-HT released causes the blood vessel upstream of the injury site to vasoconstrict so the blood flow at the injury site is reduced. script REPEAT OR MOVE ON TO THE NEXT PAGE script default syLockScreen "bond1" "bond2" "bond3" "bond4" "bond5" leavePage leavePage words bond1 bond2 bond3 bond4 bond5 ligase backPage ID 30 default buttonUp buttonUp default NextPage default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page Animate6 Animate words EPEAT OR MOVE ON TO THE NEXT PAGEadjacent fibrin monomers create an extensive covalently-linked network structure.ork structure.ntly held together ACTION OF FIBRINOLIGASE: Press the 'Animate' button. : Fibrinoligase : Isopeptide bond * t$A * *'A bond1 bond3 bond5 bond2 @3 Q bond4 --removes cross the answer boxes "quest1" "quest2" leavePage leavePage quest1 quest2 A typical turnover number for a proteolytic enzyme is : 10 molecules of substrate sec 100 molecules of substrate sec 1000 molecules of substrate sec 10000 molecules of substrate sec 100000 molecules of substrate sec Thrombin has the following action : Releases fibrinopeptide B Releases fibrinopeptide A from fibrinogen Causes vasoconstriction of blood vessels Activates fibrinoligase Creates cross-links between fibrin moleculessssssssssssssss quest1 quest2 NextPage --see --questscore1 question 1. It zero Fincreases decreases depending on which answer boxes are --same applies questscores 2-20 --All forthcoming fquestions on have Jlayout except 4questscore2 B"1a" B"1b" B"1c" B"1d" B"1e" B"2a" B"2b" B"2c" B"2d" B"2e" default buttonUp buttonUp default questscore2 questscore1 "quest3" "quest4" leavePage leavePage quest3 quest4 Platelets adhere to : Endothelial cells Collagen Fibrin Red blood cells Other aggregated plateletsssss Fibrinoligase : Creates isopeptide bonds Links a-amino groups to a-COOH groups Links g-amino groups to e-COOH groups Links lysine and glutamine Links e-amino groups to g-COOH groupss quest3 quest4 NextPage 4questscore3 4questscore4 B"3a" B"3b" B"3c" B"3d" B"3e" B"4a" B"4b" B"4c" B"4d" B"4e" default buttonUp buttonUp default questscore4 questscore3 "quest5" "quest6" leavePage leavePage quest5 quest6 Which of the following associate with aggregated platelets : Prothrombin Thrombin Protofibrils are polymers of : Fibrinogen lacking fibrinopeptide A Fibrinogen lacking fibrinopeptide B Fibrinogen lacking fibrinopeptides A and B Fibrinogen Cross-linked fibrin quest5 quest6 NextPage 4questscore5 4questscore6 B"5a" B"5b" B"5c" B"5d" B"5e" B"6a" B"6b" B"6c" B"6d" B"6e" default buttonUp buttonUp default questscore6 questscore5 "quest7" "quest8" leavePage leavePage quest7 quest8 Haemostasis comprises or may comprise :::::::::::::: The process that prevents blood loss Platelet aggregation alone Coagulation alone Platelet aggregation and coagulation Aggregation of red blood cells Fibrinogen contains : 2 a(A) chains 2 b(B) chains 2 a chains 2 b chains 2 g chainsins quest7 quest8 NextPage 4questscore7 4questscore8 B"7a" B"7b" B"7c" B"7d" B"7e" B"8a" B"8b" B"8c" B"8d" B"8e" default buttonUp buttonUp default questscore8 questscore7 "quest9" "quest10" leavePage leavePage quest9 quest10 Fibrin contains : 2 a(A) chains 2 b(B) chains 2 a chains 2 b chains 2 g chains Platelets contain ::::: Vesicles containing a vasodilalator Vesicles with negative charge on inner surface Vesicles containing 5-hydroxytryptamine A nucleus Vesicles with negative charge on outer surface quest9 quest10 NextPage 4questscore9 4questscore10 B"9a" B"9b" B"9c" B"9d" B"9e" B"10a" B"10b" B"10c" B"10d" B"10e" default buttonUp buttonUp default questscore10 questscore9 "fibc" "fib3" "fib4" "fib5" "fib6" "fib1" 280, 1815 "fib2" 4650, 1815 "Thrombin removes the fibrinopeptides each fibrinogen molecule one "throm" )-930, 390 -720, 435 -405, 495 -135, 615 105, 735 420, 855 675, 975 990, 1125 1305, 1260 1515, 1290 "a1" H-150, -150 "a1" H-150, -150 "a1" H-150, -150 1650, 1215 "a1" H-200, -200 1815, 1125 "a1" H-200, -200 1905, 1095 "a1" H-200, -200 2085, 1035 "a1" H-200, -200 2295, 990 "a1" H-200, -200 2415, 930 "a1" H-200, -200 "a1" ZhorizPos 2415 4545 %, 930 4755, 900 4905, 960 5085, 1020 5235, 1095 5415, 1170 5535, 1170 5670, 1215 5910, 1275 "a3" H-100, -100 "a3" H-100, -100 "a3" H-100, -100 6075, 1185 "a3" H-200, -200 6345, 1125 "a3" H-200, -200 6570, 1080 "a3" H-200, -200 6780, 1050 "a3" H-200, -200 6885, 1025 "a3" H-200, -200 7335, 1005 "a3" H-200, -200 7695, 930 "a3" H-200, -200 7950, 900 "a3" H-200, -200 8205, 870 "a3" H-200, -200 8385, 870 "a3" H-200, -200 "a1" )1875, 1815 "a3" )6270, 1815 "The release A fragments expose sites that were previously masked." )-930, 390 -720, 435 -405, 495 -135, 615 105, 735 420, 855 675, 975 990, 1125 1305, 1260 1515, 1290 "a2" H-150, -150 "a2" H-150, -150 "a2" H-150, -150 1650, 1215 "a2" H-200, -200 1815, 1125 "a2" H-200, -200 1905, 1095 "a2" H-200, -200 2085, 1035 "a2" H-200, -200 2295, 990 "a2" H-200, -200 2415, 930 "a2" H-200, -200 "a2" 2415 4545 , 930 4755, 900 4905, 960 5085, 1020 5235, 1095 5415, 1170 5535, 1170 5670, 1215 5910, 1275 "a4" H-100, -100 "a4" H-100, -100 "a4" H-100, -100 6075, 1185 "a4" H-200, -200 6345, 1125 "a4" H-200, -200 6570, 1080 "a4" H-200, -200 6780, 1050 "a4" H-200, -200 6885, 1025 "a4" H-200, -200 7335, 1005 "a4" H-200, -200 7695, 930 "a4" H-200, -200 7950, 900 "a4" H-200, -200 8205, 870 "a4" H-200, -200 8385, 870 "a4" H-200, -200 "a2" )2205, 1815 "a4" )6570, 1815 "These are complementary nodules which they can bind non-covalently." )2520, -510 ZvertPos -510 1090 2520, 2520, 1150 360, 1815 2520, 1225 450, 1815 2520, 1300 600, 1815 2520, 1340 675, 1815 4590, 1815 4530, 1815 4425, 1815 4365, 1815 "This process produce a \, thin polymer - A PROTOFIBRIL." )-3540, 1185 -3540 -1275 , 1185 -1245, 1215 -1185, 1290 -1170, 1340 )8550, 1200 8550 7500 H-300 , 1200 6420, 1215 6345, 1275 6280, 1320 6210, 1340 )-3570, 1815 -3465, 1815 -3330, 1815 -3180, 1815 -3015, 1815 )8490, 1815 8400, 1815 8280, 1815 8175, 1815 8055, 1815 "REPEAT OR MOVE ON TO THE NEXT PAGE" default buttonUp "buttonUp Thrombin removes the fibrinopeptides of each fibrinogen molecule one at a time. words throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm The release of the fibrinopeptide A fragments expose sites that were previously masked. words throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm These sites are complementary to the sites on the end nodules to which they can bind non-covalently. words This process can continue to produce a long, thin polymer - A PROTOFIBRIL. words REPEAT OR MOVE ON TO THE NEXT PAGE words default vertPos:by vertPos:to vertPos horizPos:by horizPos:to horizPos backPage Previous default buttonUp buttonUp Previous default NextPage ID 16 default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page HAEMOSTASIS VIA THE COAGULATION SYSTEM Platelet aggregation may be enough to prevent blood loss when the damage to a blood vessel is slight and when the blood vessel is small, e.g a capillary. If the damage is extensive, as well as platelet aggregation, coagulation is triggered. Coagulation is initiated by the exposure of collagen and the release of the contents of the damaged endothelial cells. The end product of coagulation is a 3-dimensional mesh made out of fibrin covalently linked together. The size of the mesh is small enough to stop cells from escaping from the blood vessel. This fibrin mesh is commonly referred to as a blood clot. Fibrin is made from the soluble plasma protein fibrinogen through the action of thrombin. This conversion is the last stage in a cascade of proteolytic reactions which involves nearly twenty different substances.The important features of the coagulation system is that: (a) the response is rapid (b) it is localised to the site of damage...... default buttonUp buttonUp default &:&`& '@'j' (B(h( ,B-h- .B/l/ /"0H0r0 0$1J1t1 1&2L2r2 6F7l7 Factor XII Fibrinogen XII a3 HMKKKKKKK Factor XI XI aaY Factor IX Fibrin (soft clot) Thrombin Prothrombinn Factor X Fibrin (hard clot) VII aa X aaa IX aaaa Factor VIII V aaaa Factor VIII XIII aa Factor XIII VIII a Factor IIII Factor X Factor VIII Prekallikrien N3&3K3 Kallikriennn X505U5 Wound surface contact Ca ,PLL Ca ,PLL j:B:g: Ca ,PLL Ca ,PLL Ca ,PLL Ca (?) d><>a> Return ID 11 default buttonUp buttonUp default < + 1) terPage enterPage leavePage enterPage leavePage backPage Previous default buttonUp buttonUp Previous default NextPage default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page No. of molecules produced sec | T y produced sec MOVE ON TO NEXT PAGE AT ANY TIMEu 100000 fibrinnnnnn 10000 thrombinnmbin 1000 X aaaaaaaaaaa 100 IX aaaaaaaaaaaaa 10 XI aaaaaaaaaaaaaa AMPLIFICATION 1 XII aaaaaaaaaaaaa Localization of the blood clot to the site of injury is very important as more general coagulation is potentially hazardous. Localization is achieved by limiting the formation of thrombin to the negatively charged phospholipid membrane created on the surface of aggregated platelets. When platelets aggregate, 5-HT-containing vesicles fuse with the platelet plasma membrane. The inner surface of the vesicle membranes contains phosphatidylserine, a negatively charged phospholipid, so on fusing with the vesicle membrane, the outer surface of the plasma membrane becomes negatively charged. Calcium ions then bind to the negatively charged membrane. Both Xa and prothrombin have negatively charged areas and bind, through the positively charged calcium ions, to the platelet membrane. Thus high concentrations of enzyme and substrate generated on the membrane surface leading to reaction rates hundreds of times faster than in solution..... in solution.in solution.on.of times faster than in solution.es faster. a high concentration of enzyme and substrate the reaction proceeds hundreds of times faster. "Negatively charged phospholipids e.g. phosphatidyl serine, are only found on the cytoplasmic side cell membranes, %such xcome contact @blood plasma" buttonUp buttonUp Negatively charged phospholipids e.g. phosphatidyl serine, are only found on the cytoplasmic side of cell membranes, and as such do not come into contact with the blood plasma "carb" buttonUp buttonUp backPage Previous default buttonUp buttonUp Previous default NextPage default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page LOCALIZATION OF COAGULATION SYSTEM : The negatively charged areas in factor Xa and prothrombin are clusters of g-carboxyglutamate residues. These residues contain 2 negatively charged carboxyl groups.. OOC COO CH CH - NH CH CO - "carb" buttonUp buttonUp , 2895 IJK`LD+o backPage Previous default buttonUp buttonUp Previous default NextPage default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page Animate2 Animate neg10 neg11 neg12 neg13 neg14 neg15 negs1 negs2 neg17 negves2 neg17 negves1 prothrom Prothrombin HD DED ZF2FWF GXG}G throm Thrombin Thrombin "throm" "va2" "negs1" "negs2" "ca1" "ca2" "ca3" "ca4" "ca5" "ves1" "ves2" leavePage enterPage leavePage throm negs1 negs2 enterPage "throm" "va2" "negs1" "negs2" "ca1" "ca2" "ca3" "ca4" "ca5" "ves1" "ves2" ZvertPos 3785 3185 2085, 2085, 3135 2085, 3785 "negves1" "rel1" H0, -100 H0, -100 H0, -100 -1560 H-100 1830, vertpos 1830, 990 3900 3150 4965, 4965, 3900 "negves2" "rel2" H0, -100 H0, -100 H0, -100 -1450 H-100 4890, 4890, 1250 )-405, 1485 )-420, 435 )6735, -330 -255, 1515 6630, -225 -180, 495 6540, -60 60, 1590 90, 615 )1740, -330 )8565, 765 345, 690 405, 1695 1860, -45 6315, 240 8115, 915 2010, 165 555, 795 645, 1800 6210, 420 7800, 1125 2145, 435 855, 930 885, 1860 6090, 705 2220, 660 7500, 1380 5955, 885 2295, 945 1065, 1065 1170, 2025 1395, 1365 2505, 1290 5805, 1140 7170, 1545 5670, 1365 1410, 2250 2790, 1530 1725, 1530 6885, 1800 5520, 1695 3015, 1770 1995, 1785 1575, 2400 5250, 1980 6465, 2055 2295, 2115 3255, 2010 4980, 2220 3570, 2175 2535, 2280 6195, 2265 1950, 2550 3735, 2415 2835, 2535 4785, 2430 5940, 2415 4635, 2580 3840, 2565 5745, 2580 "va" 1245, 1530, 1335, 1650 "va" 1275, 1485, 1500, 1695 "va" 1380, 1425, 1710, 1725 "va" 1515, 1335, 1980, 1770 "va" 1680, 1200, 2340, 1815 "va" 1890, 1080, 2760, 1875 "va" 2115, 975, 3180, 1920 "va" 2370, 810, 3645, 1980 "va" 2565, 660, 4110, 2070 "va" 2880, 495, 4590, 2175 3195, 330, 5190, 2190 H0, 100 H0, 100 H0, 100 H0, 100 "xa" )-915, 1035 "xa" -780, 1080 "xa" -675, 1110 "xa" -480, 1155 "xa" -345, 1200 "xa" -285, 1230 "xa" -135, 1260 "xa" 75, 1320 "xa" 225, 1380 "xa" 375, 1425 "xa" 525, 1470 "xa" 720, 1545 "xa" 900, 1590 "xa" 1035, 1635 horizPos 1035 2535 "xa" ", 1635 "xa" 2835, 1665 "prothrom" )8545, 1650 8545 3645 H-350 }, 1650 )3840, 1650 )3645, 1785 3960, 1620 3660, 1785 4110, 1620 3720, 1785 4320, 1620 "pro" 3930, 1785 4425, 1620 4080, 1695 4560, 1620 4110, 1485 4755, 1620 4170, 1380 4845, 1605 4335, 1185 4440, 795 4575, 525 4860, 315 5010, 135 5145, -105 5280, -255 5325, -375 5475, -495 5550, -585 5580, -690 default buttonUp buttonUp throm negs1 negs2 negves1 negves1 negs1 vertpos negves2 negves2 negs2 prothrom prothrom prothrom throm throm throm throm throm throm throm throm default horizPos:by horizPos:to horizPos vertPos:by vertPos:to vertPos The final stage of coagulation involves proteolysis but results in the formation of a fibrous clot rather than a further proteolytic enzyme. Fibrinogen is a soluble plasma protein and is converted to an insoluble derivative, fibrin, by the final proteinase in the coagulation cascade, thrombin. Fibrin is insoluble and aggregates in an ordered way to form a 3-dimensional network with a mesh size similar in size to a red blood cell. backPage Previous default buttonUp buttonUp Previous default NextPage default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page CONVERSION OF FIBRINOGEN TO FIBRIN Fibrinogen is a soluble plasma protein and is converted to an insoluble derivative, fibrin, by the final proteinase in the coagulation cascade, thrombin. Fibrin is insoluble and aggregates in an ordered way to form a 3-dimensional network with a mesh size similar in size to a red blood cell. photorbc "photo" default buttonUp buttonUp photo default photo "photo" default buttonUp buttonUp photo default Trapped erythrocyte backPage Previous default buttonUp buttonUp Previous default NextPage default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page FIBRINOGEN STRUCTURE: Fibrinogen has a molecular mass of 340,000 and consists of three pairs of polypeptide chains of similar size - a(A), b(B) and g, each containing approximately 500 amino acids. The arrangement of the chains is as follows::: 4 * 1 : Disulphide bondd B : Fibrinopeptide BA A : Fibrinopeptide AA backPage Previous default buttonUp buttonUp Previous default NextPage default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page FIBRINOGEN SHAPE: Electron micrographs of fibrinogen shows it to have a trinodular structure. It can be represented diagramatically as follows: fibgen photo "photo2" default buttonUp buttonUp photo2 default Fibrinopeptide A Fibrinopeptide B Thrombin has a very limited action on fibrinogen - it cleaves only 4 peptide bonds out of approximately 3000 present. These bonds are broken in 2 stages. First thrombin cleaves a single Arg-Gly bond near the terminus of the a(A) chain releasing a small (15 amino acid) soluble fragment called FIBRINOPEPTIDE A. The fibrinopeptides mask sites that mediate intermolecular association. ACTION OF THROMBIN: photo2 "photo2" default buttonUp buttonUp photo2 default ^ 6 [ Fibrinogen Molecules "fibc" "fib3" "fib4" "fib5" "fib6" "fib1" 280, 1815 "fib2" 4650, 1815 leavePage leavePage words " ,&6,@2J8r8 throm backPage Previous default buttonUp buttonUp Previous default NextPage default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page words EPEAT OR MOVE ON TO THE NEXT PAGEce a long, thin polymer - A PROTOFIBRIL.y can bind non-covalently. Animate3 Animate "-` P P1` P ,3` P Z7` P : Masked binding site |9T9y9 : Complementery binding site : Thrombinn backPage Previous default buttonUp buttonUp Previous default NextPage default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page RELEASE OF FIBRINOPEPTIDE B AND SIDE TO SIDE POLIMERIZATION OF PROTOFIBRILS: Protofibril formation results in fibres two fibrinogen molecules thick. A fibrin clot, however, consists of fibres which may be tens of fibrin molecules thick. The formation of these thick fibres occurs after the release of fibrinopeptide B. The release of fibrinopeptide B allows side-to-side polymerization of protofibrils into bundles of varying thickness. The molecule produced as a result of the release of both fibrinopeptides A and B is a fibrin monomer. This monomer polymerizes to produce a fibrin polymer. bundles of varying thickness. Once fibrinopeptide B has been cleaved the parent molecule is known as fibrin. backPage Previous default buttonUp buttonUp Previous default NextPage default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page FORMATION OF FIBRIN NETWORK: The two-stage release of the fibrinopeptides is important in allowing the formation of a 3-dimensional insoluble fibrin network. The production of protofibrils alone leads to the formation of a viscous solution but not to the formation of a gel. A gel, in which fibres form a 3-dimensional net, is required for coagulation. The 3-dimensional net is formed when protofibrils or bundles of protofibrils are incorporated into one protofibril bundle at one end and another bundle at its other end, forming cross-strands. This allows network formation. network formation.twork formation.t one end and incorporated into another bundle at its other end, forming cross-strands. This allows network formation. "b10" "proto1" -2970, -995 -2970, 2060 "proto2" -2970, 5835 leavePage leavePage words proto1 proto proto2 throm proto z"o 6(` P T-` P &/` P T3` P &5` P T9` P proto1 ^A~ 3 PF~ 3 proto2 ^a~ 3 \l~ 3 backPage Previous default buttonUp buttonUp Previous default NextPage default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page words Animate4 Animate "Bundle protofibrils." "b1" )-389, -509 ZvertPos -509 "b1" -389, "Second bundle { joins )one "b2" )8400, 3045 "b2" H-580, -130 "b2" H-580, -130 "b2" H-580, -130 "b2" H-580, -130 "b2" H-580, -130 "b2" H-580, -130 "b2" H-580, -130 "b2" H-580, -130 "b2" H-580, -130 "b2" H-580, -130 "b2" H-580, -130 "b2" H-580, -130 "b2" H-580, -130 "b2" H-580, -130 "b2" H-580, -130 the other "b3" )150, 5800 5800 3600 H-200 "b3" 150, protfibrils form a mesh "b4" )-1670, 1440 horizPos -1670 -270 "b4" #, 1440 "REPEAT OR MOVE ON TO THE NEXT PAGE" default buttonUp buttonUp words Bundle of protofibrils. words Second bundle of protofibrils joins to first at one end. words A third bundle joins to the other end of the second bundle. words A fourth bundle of protfibrils joins to the second bundle at one end and the third bundle at the other end to form a mesh system. words REPEAT OR MOVE ON TO THE NEXT PAGE words default horizPos:by horizPos:to horizPos vertPos:by vertPos:to vertPos "b10" "proto1" -2970, -995 -2970, 2060 "proto2" -2970, 5835 "Thrombin cleaves the fibrinopeptide B fragments gen, exposing sites that were previously masked." "throm" )-960, 915 -600, 1100 -240, 1285 120, 1470 300, 1365 "b1" H-150, -150 360, 1290 "b1" H-150, -150 495, 1245 "b1" H-150, -150 "b1" 435, 1995 ZhorizPos 2640 $, 1245 2640, 1245 3020, 1320 3400, 1395 3780, 1470 3780, 1485 "b3" H0, -250 "b3" H0, -250 3915, 1395 "b3" H0, -250 "b3" H0, -250 3990, 1290 "b3" H0, -250 "b3" H0, -250 4155, 1245 "b3" H0, -250 "b3" H0, -250 "b3" 4140, 1995 4155 6540 , 1245 6540, 1245 7005, 1350 7470, 1455 7575, 1410 "b5" H150, -150 7725, 1320 "b5" H150, -150 7920, 1260 "b5" H150, -150 8160, 1200 "b5" H150, -150 8325, 1095 "b5" 7830, 1995 8325, 1095 8475, 1005 )8475, 3345 7926, 3255 7377, 3165 6828, 3075 6279, 2985 5730, 2895 5655, 2925 H250, 250 H250, 250 5550, 2985 H250, 250 H250, 250 5475, 3030 H250, 250 H250, 250 5355, 3090 H250, 250 H250, 250 5280, 3120 H250, 250 H250, 250 6375, 2877 5280 3435 H-250 , 3120 3435, 3120 3086, 3067 2737, 3015 2388, 2962 2040, 2910 1875, 2940 "b8" H-150, 250 "b8" H-150, 250 1695, 2985 "b8" H-150, 250 "b8" H-150, 250 1455, 3060 "b8" H-150, 250 "b8" H-150, 250 1245, 3135 "b8" H-150, 250 "b8" H-150, 250 1020, 3180 "b8" H-150, 250 "b8" H-150, 250 705, 3225 "b8" H-150, 250 "b8" H-150, 250 435, 3240 "b8" H-150, 250 "b8" H-150, 250 210, 3255 "b8" H-150, 250 "b8" H-150, 250 -120, 3255 "b8" 2670, 2892 -270, 3240 -540, 3225 -810, 3225 -1020, 3240 )-960, 915 -600, 1100 -240, 1285 120, 1470 300, 1365 "b2" H-200, -200 360, 1290 "b2" H-200, -200 495, 1245 "b2" H-200, -200 "b2" 810, 1995 2640 , 1245 2640, 1245 3020, 1320 3400, 1395 3780, 1470 3780, 1485 "b4" H0, -250 "b4" H0, -250 3915, 1395 "b4" H0, -250 "b4" H0, -250 3990, 1290 "b4" H0, -250 "b4" H0, -250 4155, 1245 "b4" H0, -250 "b4" H0, -250 "b4" 4515, 1995 4155 6540 , 1245 6540, 1245 7005, 1350 7470, 1455 7575, 1410 "b6" H200, -200 7725, 1320 "b6" H200, -200 7920, 1260 "b6" H200, -200 8160, 1200 "b6" H200, -200 8325, 1095 "b6" 8205, 1995 8325, 1095 8475, 1005 )8475, 3345 7926, 3255 7377, 3165 6828, 3075 6279, 2985 5730, 2895 5655, 2925 "b9" H250, 250 "b9" H250, 250 5550, 2985 "b9" H250, 250 "b9" H250, 250 5475, 3030 "b9" H250, 250 "b9" H250, 250 5355, 3090 "b9" H250, 250 "b9" H250, 250 5280, 3120 "b9" H250, 250 "b9" H250, 250 "b9" 6015, 2892 5280 3435 H-250 , 3120 3435, 3120 3086, 3067 2737, 3015 2388, 2962 2040, 2910 1875, 2940 "b7" H-150, 250 "b7" H-150, 250 1695, 2985 "b7" H-150, 250 "b7" H-150, 250 1455, 3060 "b7" H-150, 250 "b7" H-150, 250 1245, 3135 "b7" H-150, 250 "b7" H-150, 250 1020, 3180 "b7" H-150, 250 "b7" H-150, 250 705, 3225 "b7" H-150, 250 "b7" H-150, 250 435, 3240 "b7" H-150, 250 "b7" H-150, 250 210, 3255 "b7" H-150, 250 "b7" H-150, 250 -120, 3255 "b7" 2325, 2892 -270, 3240 -540, 3225 -810, 3225 -1020, 3240 "The exposed bind complementary outer nodules molecules other protofibrils." H0, 200 H0, 200 H0, 200 H0, 200 H0, 200 H0, 200 H0, 100 H0, -100 H0, 100 H0, -100 H0, 100 H0, -100 H0, 100 H0, -100 H0, 100 H0, -100 way bundles are formed varying thickness depending on collisions take place." H0, -400 H0, -400 H0, -400 H0, -400 H0, -400 H0, -400 H0, -400 H0, -400 H0, -200 " This animation shows building up a ribbon. In reality they $ up "REPEAT OR MOVE ON TO THE NEXT PAGE" default buttonUp 7buttonUp words proto1 proto proto2 Thrombin cleaves the fibrinopeptide B fragments from the fibrinogen, exposing sites that were previously masked. words throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm throm The exposed sites bind to complementary sites on the outer nodules of fibrin molecules of other protofibrils. words proto1 proto1 proto1 proto1 proto1 proto1 proto1 proto proto1 proto proto1 proto proto1 proto proto1 proto In this way bundles of protofibrils are formed of varying thickness depending on the number of collisions that take place. words proto2 proto2 proto2 proto2 proto2 proto2 proto2 proto2 proto2 This animation shows the protofibrils building up to a ribbon. In reality they build up into thick bundles. words REPEAT OR MOVE ON TO THE NEXT PAGE words default horizPos:by horizPos:to horizPos System Times New Roman Arial Haemostasis Arial j xsuJ Times New Roman utNpyxjz Times New Roman Times New Roman Times New Roman Times New Roman Wingdings Wingdings Symbol Times New Roman Wingdings -- Puts the mode hides menus EnterBook Reader sysRuntime c"Edit" c"Text" c"File" c"Help" sysScreenLock LeaveBook EnterBook LeaveBook EnterBook sizetopage sysScreenLock LeaveBook Times New Roman Times New Roman Times New Roman Times New Roman Times New Roman Symbol Times New Roman MS Sans Serif System Courier Arial Symbol Arial System Symbol Times New Roman :PRINTLAYOUT Symbol Times New Roman Times New Roman Times New Roman Times New Roman *%,%,% "*#z$ backPage Previous default buttonUp buttonUp Previous default NextPage default buttonUp buttonUp default Dialog Plasma - fluid containing most coagulation factors and in which cells and platelets circulate. CROSS SECTION OF A BLOOD VESSELLLLLLLLL Collagen Endothelial cell lining cells Put "Endothelial cell lining - continuous monolayer cells completely surrounding F lumen." "Dialog" mouseEnter mouseEnter Endothelial cell lining - continuous monolayer of cells completely surrounding the lumen. Dialog collagen Put "Collagen - blood vessel wall artery/vein : connective tissue capillary. Has no contact fcirculating "Dialog" mouseEnter mouseEnter Collagen - in blood vessel wall if artery/vein : in connective tissue if capillary. Has no contact with circulating blood Dialog plasma "Plasma - fluid containing most coagulation factors which cells platelets circulate." "dialog" mouseEnter mouseEnter Plasma - fluid containing most coagulation factors and in which cells and platelets circulate. dialog Put "Erythrocyte / blood cell." "Dialog" mouseEnter mouseEnter Erythrocyte / red blood cell. Dialog platelets Put "Platelet - has a fundamental role haemostasis." "Dialog" mouseEnter mouseEnter Platelet - has a fundamental role in haemostasis. Dialog $ 4 4 Move the mouse onto each part of the blood vessel. ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page Basic Basic :PHYSSIZE Teaching and Learning Technology Programme produced by the Hemostasis Dr. John M. Basford & Andrew N. MacLennan default buttonUp buttonUp default Start Basic You can distribute the unmodified material freely and modify it to your own requirements. However, we ask the following: 1. By all means give yourself credit for your work in your books but please leave this page unaltered in this book. 2. It is important that teaching material of this kind is disseminated as widely as possible, so please ensure that your material is also freely available. 3. Please send a copy of any modified or expanded versions of this program to Dr J.M Basford, Department of Biochemistry, University of Wales, Cardiff, CF1 1ST , Tel 44 222-874119 Fax 44 222-874116. Internet Basford @Cardiff.ac.uk default buttonUp buttonUp default Continue Basic Buttons Used In The Following Pagess ExitProgram backPage NextPage FirstPage 1st Page Move to the next page Return to previous page Return to the first page of Exit to Windows Animate Animate Animates the sequence of events on that page These are words that are scattered round the text and are shown in italic and bold type and are larger than the surrounding text. They become active when the mouse operated cursor is placed over them. Try pressing this Hotword now! -- Puts the sentence quotation marks a dialog box which can be removed Hclicking "Activating a HOTWORD will present you dthat may contain definitions, references, hints tips, prompts other forms encouragement. Press OK buttonDown buttonDown Activating a HOTWORD will present you with a dialog box that may contain definitions, references, hints and tips, prompts or other forms of encouragement. Press OK to continue ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? NextPage default buttonUp buttonUp default FirstPage buttonUp buttonUp 1st Page Go on to the next page by clicking the button below: Hotwords - J p PLATELET STRUCTURE Cytosol - Platelets do not have a nucleus as they are fragments from cells known as megakarocytes. backPage Previous default buttonUp buttonUp Previous default NextPage default buttonUp buttonUp default Intracellular vesicles - they contain 5-hydroxytrypamine (a vasoconstrictor). Membrane. There are sites on the membrane that have affinity for collagen. ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page Glycogen granule Mitochondrion photo3 "photo3" default buttonUp buttonUp photo3 default Platelets "photo3" default buttonUp buttonUp photo3 default Photo 4drop < 15 ; + 1) terPage enterPage leavePage enterPage leavePage wound THE PURPOSE OF HAEMOSTASIS Haemostasis is the name given to systems that prevent blood loss. The mechanisms involved are important as without them the smallest injury could lead to death. There are two main mechanisms by which haemostasis occurs: (a) Platelet aggregation (b) Coagulation In the following pages these two processes will be discussed in detail and shown using animation techniques. At the end there will be a quiz on the material covered. Your score and the answers to questions answered incorectly will be given at the end of the quiz. backPage Previous default buttonUp buttonUp Previous default NextPage default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page MOVE ON TO NEXT PAGE AT ANY TIME "p1b" "p2b" "p3b" "p4b" "p5b" "p6b" "rp2" -960, 2805 "p1" )1860, 3660 "p2" )1080, 3645 "p3" )150, 3660 "p4" )-330, 3570 "rp1" )3330, 2655 "rp4" -3840, 2685 "rp5" -285, 3090 "con" "vessel" Put "" leavePage leavePage vessel script /(0X0 CfL2M P.Q^Q PLATELET AGGREGATIONN Press the 'Animate' button backPage Previous default buttonUp buttonUp Previous default NextPage default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page vessel cell1 67. G Script "rp4" buttonUp buttonUp rbc12 rbc13 rbc11 screen enlarge lplate drop1 Animate1 Animate backPage ID 11 default buttonUp buttonUp default NextPage default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page RAPID RESPONSE OF COAGULATION SYSTEM : The coagulation pathway leading to the formation of the fibrin mesh has many steps which enables it to act as a biochemical amplifier. This amplifier is sometimes referred to as a cascade. Seven of the substances involved in the pathway are inactive forms of enzymes that are activated by the preceding enzymes in the cascade. An average turnover number for a proteolytic enzyme is ten substrate molecules per second. This means that the first enzyme will convert ten substrate molecules per second; the 10 enzyme molecules produced will then each be capable of generating the third enzyme at the rate of 10 molecules per second i.e. 100 molecules per second overall. The amplification factor is thus approx 10 for each stage. This causes a large response in a very short time. large response in a very short time. hort time. backPage Previous default buttonUp buttonUp Previous default NextPage default buttonUp buttonUp default ExitProgram "Really quit?"\ f"Yes" SysSuspendMessages buttonUp buttonUp Really quit? FirstPage buttonUp buttonUp 1st Page HAEMOSTASIS VIA PLATELET AGGREGATION Platelets are unpigmented, enucleated blood cells that have fragmented from larger cells called megakarocytes. They have many vesicles containing a physiologically active substance called 5-hydroxytryptamine (5-HT) -see diagram on following page. In a damaged section of blood vessel the platelets will adhere to the exposed collagen surrounding the vessel wall and then to other platelets. In this way a plug is formed that can stop minor bleeding. The association between platelets and collagen is mediated by the large multimeric plasma protein - von Willebrandt factor. As the platelets aggregate they release the 5-HT causing vasoconstriction of the blood vessel, and in doing so reduce the blood flow at the site of injury. If the damage is extensive then the coagulation system is triggered. ed. 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