分析报告课件

1、分析报告,In people acclimated to high altitudes, the concentration of 2,3-diphosphoglycerate (2,3-DPG) in the blood is increased, which allows these individuals to deliver a larger amount of oxygen to tissues under conditions of lower oxygen tension. Initially given high dose O2 through mask Electron tr

2、ansport Because there are many more oxygen molecules present in a given volume when under pressure, hyperbaric oxygen dissolves in the blood in far greater amounts enabling it to be transported to the cells. Hyperbaric oxygen (HBO) also helps rid haemoglobin of the tenacious CO molecules, freeing it

3、 up for normal use once more. The actual amount of oxygen molecules at a pressure of 3ata (20msw) in a fixed volume is equal to 3 times the amount at the surface.In cases of carbon monoxide poisoning, it normally takes over four hours for the amount of CO in the body to fall by one half, during whic

4、h time the tissues are hypoxic due to replacement of O2Hb with COHb. Hyperbaric oxygen at 3ata reduces this to 20 minutes, during which time the extra oxygen dissolved in the blood alleviates hypoxia.,分析报告,Prostaglandins act in a manner similar to that of hormones, by stimulating target cells into a

5、ction. differ from hormones in that they act locally, near their site of synthesis, and they are metabolized very rapidly the same prostaglandins act differently in different tissues,分析报告,分析报告,Hemostasis & Thrombosis: Hemophilia Beth A. Bouchard BIOC 212: Biochemistry of Human Disease Spring 2005,分析

6、报告,分析报告,HEMOSTASIS,1). INITIATION Vessel wall endothelial cells and subendothelial components 2). LOCALIZATION Platelets circulating cellular elements 3). PROPAGATION/AMPLIFICATION Plasma coagulation proteins (factors) 4). TERMINATION Plasma coagulation protein inhibitors 5). ELIMINATION Fibrinolyti

7、c system,分析报告,分析报告,BLOOD COAGULATION,分析报告,分析报告,BLOOD COAGULATION (CONT.),Deficiencies in all of the factors, except factor XII, lead to a bleeding tendency in the affected individual Described as a waterfall or cascade sequence of zymogen (pro-enzyme) to enzyme conversions, with each enzyme activati

8、ng the next zymogen in the seqeunce Activated factor enzymes are designated with an “a”, e.g. factor Xa,分析报告,Common constituents of coagulation complexes,Vitamin K-dependent (VKD) zymogen,Ca2+,Appropriate membrane surface,- activated platelets (VIIIa/IXa complex, Va/Xa complex),subendothelial cells,

9、 typically fibroblasts (TF/VIIa complex),Protein cofactor,分析报告,分析报告,Common constituents of coagulation complexes,Vitamin K-dependent (VKD) zymogen,Ca2+,Appropriate membrane surface,- activated platelets (VIIIa/IXa complex, Va/Xa complex),subendothelial cells, typically fibroblasts (TF/VIIa complex),

10、Protein cofactor,分析报告,Functional Domains of the Vitamin K- dependent Zymogens,分析报告,Gamma (g)-carboxyglutamic acid,分析报告,VITAMIN K,Group of related, fat soluble compounds, which differ in the number of side-chain isoprenoid units Plant derived (vitamin K1) and synthesized by intestinal bacteria (vitam

11、in K2) The reduced form of vitamin K2 (vitamin KH2) is required for the post-translational, gamma-carboxylation of several proteins involved in blood clotting,分析报告,Formation of Gla residues subsequent to protein synthesis (post-translational),分析报告,Vitamin K deficiency,Deficiency of vitamin K is rare

12、 because of its wide distribution in nature, and its production by intestinal bacteria Found in individuals with liver disease and fat malabsorption - it is associated with bleeding disorders Newborn infants (especially preemies) are also at risk - Placenta is insufficient in the transfer of materna

13、l vitamin K - Concentration of circulating vitamin K drops immediately after birth, and it recovers upon absorption of food - Gut of the newborn is sterile Thus, newborns are given an injection of vitamin K following birth.,分析报告,Common constituents of coagulation complexes,Vitamin K-dependent (VKD)

14、zymogen,Protein cofactor,Ca2+,Appropriate membrane surface,- activated platelets (VIIIa/IXa complex, Va/Xa complex),subendothelial cells, typically fibroblasts (TF/VIIa complex),分析报告,Relevance of complex formation and its constituents,分析报告,Common constituents of coagulation complexes,Vitamin K-depen

15、dent (VKD) zymogen,Protein cofactor,Ca2+,Appropriate membrane surface,- activated platelets (VIIIa/IXa complex, Va/Xa complex),subendothelial cells, typically fibroblasts (TF/VIIa complex),* Express anionic phospholipids and membrane receptors for coagulation proteins. In platelets, the expression o

16、f this membrane surface is activation-dependent.,分析报告,Thrombin Cleaves Fibrinogen Activates Platelets Activates procofactors (FV and FVIII) Activates zymogens (FVII, FXI and FXIII),分析报告,分析报告,Intrinsic Pathway of Blood Coagulation,No factors extrinsic to the blood are involved Clinical test to assess

17、 the functionality of this pathway is the activated partial thromboplastin time (aPTT) Kaolin and cephalin are added to the test plasma sample The normal range is 30 50 seconds (varies slightly depending on the laboratory) Prolongations in the aPTT are observed in deficiencies of factors XI, IX, VII

18、I, X, and V, prothrombin, or fibrinogen. Used to test for common congenital hemophilias (deficiencies in IX, VIII, or XI) and to monitor heparin treatment,分析报告,Extrinsic Pathway of Blood Coagulation,Extrinsic refers to tissue factor, which is expressed on subendothelial cells Clinical test to assess

19、 the functionality of this pathway is the prothrombin time (PT) Lipidated tissue factor is added to test plasma sample The normal range is 10-15 seconds (varies slightly depending on the laboratory) Prolongations in the PT are observed in deficiencies of factors VII, X, V, prothrombin, or fibrinogen

20、. Used to test for the rare congenital deficiencies in these factors: More often it is used to diagnose acquired bleeding disorders resulting from vitamin K deficiency, oral anticoagulants (e.g. warfarin), and liver disease,分析报告,Thrombin Time (TT),In this test, thrombin is added to plasma The normal

21、 range is 10-15 seconds (varies slightly depending on the laboratory) Prolongations in the TT are observed in congenital fibrinogen deficiency or acquired fibrinogen deficiency resulting from consumption of fibrinogen in DIC (disseminated intravascular coagulation), or may occur following treatment

22、with fibrinolytic drugs,分析报告,Hemophilias A and B,Hemophilias A and B are cause by deficiencies in factors VIII or IX, respectively Affect 1 in 10,000 males Inherited as a recessive X-linked trait (Mom would be an unaffected carrier) Treated by administration of factor VIII or factor IX concentrates

23、Recombinant factor VIII or XI Gene therapy trials,分析报告,HEMOSTASIS (CONT.),1). INITIATION Vessel wall endothelial cells and subendothelial components 2). LOCALIZATION Platelets circulating cellular elements 3). PROPAGATION/AMPLIFICATION Plasma coagulation proteins (factors) 4). TERMINATION Plasma coa

24、gulation protein inhibitors 5). ELIMINATION Fibrinolytic system,分析报告,INHIBITORS,分析报告,INHIBITORS (cont.),分析报告,FIBRINOLYSIS,分析报告,FIBRINOLYSIS (CONT.),分析报告,Bleeding disorders can span the spectrum from weeping blood vessels to full-fledged internal and external hemorrhage,Genetic defects: platelet abno

25、rmalities blood vessel wall abnormalities clotting factor deficiencies (hemophilias) excess clot breakdown (fibrinolysis),Acquired defects: liver disease (site of clotting factor synthesis) vitamin K deficiency autoimmune disease (platelet destruction) trauma,分析报告,Bleeding disorders can span the spe

26、ctrum from weeping blood vessels to full-fledged internal and external hemorrhage,Treated by factor replacement,分析报告,Thrombosis can be manifested as a transient, short-term or episodic event in individuals with chronic or recurring clotting. It is the major cause of both stroke and heart attacks.,Genetic defects: clotting factor INHI