Department of medical physiology 3 rd week

Transcription

1 Department of medical physiology 3 rd week Semester: winter Study program: Dental medicine Lecture: RNDr. Soňa Grešová, PhD. Department of medical physiology Faculty of Medicine PJŠU

2 Department of medical physiology 3 rd week 1. Platelets morfology, production, account, function 2. Blood clotting, haemocoagulation factors 3. Group antigens, blood transfusion

3 1. Prevention of Blood Clotting in the Normal Vascular System Intravascular Anticoagulants Endothelial Surface Factors a) the smoothness of the endothelial cell surface -NO, PGI 2 inactivate receptors of Tr againts aggregation, - ADP adenosin diphosphatase against adherence of Tr b) glycocalyx - repels clotting factors and platelets, thereby preventing activation of clotting c) thrombomodulin which binds thrombin and activates a plasma protein, protein C - anticoagulant by inactivating activated Factors V and VIII.

4 1. Prevention of Blood Clotting in the Normal Vascular System Intravascular Anticoagulants Antithrombin Action of Fibrin and Antithrombin III. alpha-globulin called antithrombin III or antithrombin-heparin cofactor Heparin combines with antithrombin III, the effectiveness of antithrombin III for removing thrombin increases - anticoagulant by inactivating activated Thrombin and Factors XII, XI, X and IX Activation of Plasminogen to Form Plasmin injured tissues and vascular endothelium release a powerful activator called tissue plasminogen activator (t-pa)

5 1. Platelets morfology, production, account, function Platelets or thrombocytes are small colorless, non nucleated cells Shape is spherical or rod shaped and become oval or disc shaped when inactivated volume 6-9 fl (10-15 l) average 2-4 µl < microthrombocyts > macrothrombocyts thickness 1µm Platelets x10 9 /l ( /mm 3 ) Lifespan 10 days TROMBOCYTOSIS intense muscle work, altitude -hypoxia, dehydration, myeloproliferative disorders. TROMBOCYTOPENIA insufficient production, overbleeding < l, functionless < l,

6 Cell Lines in Blood Cell Formation (Hematopoiesis) Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.

7 1. Platelets structure Cell Membrane of Platelet It is 6 nm thick and contain lipids - phospholipids, cholesterol, glycolipids - Carbohydrates(glycocalyx) Glycopropteins -form a receptor for ADP and thrombin - receptors (glykoproteins): GP Ib adherence; GP IIb a GP IIIa - aggregation Phospholipids - accelerate clotting reactions. - form precursors for thromboxane A 2

8 1. Platelets structure Cytoplasm Tubular systems Dense tubular system - it is the main calcium storage Opened tubular system - it is creatived by numeorus invaginations and it is for releasing of content from granules Fibrous structurs Submembrane filaments and mikrotubuls - they maintain the discoid shape and position of organels in nonactive platelets Cytoplasmatic mikrofilaments - they are responsible for contraction at the releasing granular content

9 1. Platelets structure Cytoplasm Proteins The major proteins present are contractile proteins which are responsible for the contraction of platelets: Actin Myosin Thrombosthenin Fibrin-stabilizing factor (PF XIII) : clotting factor Platelet derived growth factor (PDGF) : helps repair damaged vascular walls. Enzymes The enzymes present are adenosine triphosphatase and the enzymes necessary for the synthesis of prostaglandin. Hormones Adrenaline vascular and Serotonin local tissue reactions Histamine Chemical substances: Calcium ions Mg- ions. Adenosine triphosphate (ATP) Adenosine diphosphate (ADP)

10 1. Platelets structure Cytoplasm Granules α granula - PF 1 proaccelerin (f.v) - PF2 β - thromboglobulin, which supports the transformation of fibrinogen to fibrin - PF 3 thromboplastic factor - PF 4 antiheparine factor - PF 5 platelet fibrinogen - factor of permeability, which increases permeability of the vessel wall δ granula (dense granules) - ADP and ATP - Ca2+ - Serotonine λ- granula - they are lysosomes and contain the acidic hydrolases, glucuronidese, β- galactosidase, elastase, colagenese and others

11 1. Platelets function PARTIPICIPATION ON HEMOSTATIC PROCESSES - application of the mechanical and humoral action PARTICIPATION ON INFLAMMATORY PROCESSES - realesing of platelet activating factor (PAF), which is mediator of inflammatory and alergic reactions - activation of phospholipase A2 and production of the important inflammatory substances (prostaglandins, leucotriens, thromboxan)

12 2. Blood clotting, haemocoagulation factors 1. Vessel reactions in the place of damage 2. Platelet activity a) adhesion b) change of the shape and releasing reaction c) aggregation 3. Haemocoagulation Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.

13 2. Blood clotting, haemocoagulation factors 1. Vessel reactions in the place of damage VASOCONSTRICTION REFLEX - it is allowed by the smooth muscle cell contraction as the direct response of the vessel wall for damage - sympathetic mediates it and duration of this event is some minutes or hours HUMORAL - substances producing vasoconstriction are from platelets mainly serotonine, but also substances as adrenaline, thromboxan A2, fibrinopeptids and fibronektine.

14 2. Blood clotting, haemocoagulation 2. Platelet activity - it consists in contact with collagen fibres through specific receptors on the platelet membrane (GP Ib) and with the certain binding places of the collagen molecule a) adhesion: factors Negative influence: production of the instable prostacykline (PGI2), which is produced by endothelial cells of the vessel wall Positive influence: von Willebrand s factor, thrombin, ADP

15 2. Blood clotting, haemocoagulation factors b) change of the shape and releasing reaction - platelets acquire the spheric shape - by the mechanism of the active contraction (presence of actin and myosin in the cytoplasma) pseudopodia subendothelium fibres-bound are produced SECRETION - ADP stimulates the platelet aggregation - vonwillebrand s factor supports the platelet adhesion - fibronektin supports the platelet adhesion - serotonin supports the vasoconstriction - growth factor (PDGF Platelet-derived Growth Factor) mitogenic effect - thromboxan A2 supports the vasoconstriction and platelet aggregation - PAF (Platelet Activating Factor) activates not only next platelets but also phagocytes

16 2. Blood clotting, haemocoagulation c) aggregation factors - Primary phase of aggregation aggregation is in progress after adhesion of the first platelet layer on the vessel wall. This phase is still reversible. - binding of platelets by fibrinogen through fibrin receptors (GP IIb/IIIa) COMPLEX of AGGREGATION: secondary phase of aggregation (irreversible). -binding between platelets and fibrinogen is stronger under influence of thrombospondine (protein from α-granules)

17 3. 2. Blood clotting, haemocoagulation factors Haemocoagulation - Haemocoagulation factors Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.

18 2. Blood clotting, haemocoagulation 3. Haemocoagulation factors a) Intrinsic pathway b) Extrinsic pathway

19 3. Haemocoagulation a) Intrinsic pathway Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.

20 3. Haemocoagulation - Extrinsic pathway Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.

21 3. Haemocoagulation Polymerization of fibrinogen Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.

22 3. Fibrinolysis

23 Bleeding Time Duke s Method Make a small incision or finger prick, and dab the end of the finger on a paper every 30 sec. until the bleeding stops. Count the number of the blots and divide by 2 Normal bleeding time is 1 6 min. Abnormal bleeding time: Blood vessel defect, platelet defect, thrombocytopenia

24 Clotting Time To collect blood in a chemically clean glass test tube and then to tip the tube back and forth about every 30 seconds until the blood has clotted. By this method, the normal clotting time is 6 to 10 minutes

25 3. Group antigens, blood transfusion Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.

26 3. Group antigens, blood transfusion Heredity of blood groups Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier. Copyright: Kujanik,S., & col. (1998). Practical lesson in physiology. Košice: Medical faculty UPJS.

27 Rh Blood Types Rh antigens are designated C,D, E, c, d, and e Rh positive (D antigen) Rh negative (person who does not have type D antigen)

28 Blood Type Pathology Hemolytic Disease of the Newborn (Erythroblastosis Fetalis) the mother is Rh negative and the father Rh positive The baby has inherited the Rh-positive antigen from the father, and the mother develops anti-rh agglutinins from exposure to the fetus s Rh antigen

29 3. Principles of the blood transfusion plasma from donor cannot clott blood cells of recipient give blood the same group, subgroup and Rh factor 1. Cross-matching 2. Biological examination 3. In the case negative reaction, the biological examination repeat still 2x 4. After the stopping of transfusion to monitor pacient 2-4 hours is needed