Department of medical physiology3rd week

Semester: winterStudy program: Dental medicineLecture: RNDr. Soňa Grešová, PhD.Department of medical physiologyFaculty of Medicine PJŠU

Department of medical physiology3rd week

1. Platelets – morfology, production, account, function

2. Blood clotting, haemocoagulation factors

3. Group antigens, blood transfusion

1. Prevention of Blood Clotting in the Normal Vascular System—Intravascular Anticoagulants

Endothelial Surface Factors

a) the smoothness of the endothelial cell surface-NO, PGI2 – 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 plasmaprotein, protein C

- anticoagulant by inactivating activated Factors V and VIII.

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)

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

thickness 1µm

Platelets 150-350x109/l (150 000-300 000/mm3)

Lifespan 10 days

TROMBOCYTOSIS intense muscle work, altitude -hypoxia, dehydration, myeloproliferative disorders.

TROMBOCYTOPENIA – insufficient production, overbleeding<20.109l, functionless < 50.109l,

< microthrombocyts

> macrothrombocyts

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.

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 A2

Cytoplasm • Tubular systemsDense tubular system- it is the main calcium storageOpened tubular system- it is creatived by numeorus invaginations and it is for

releasing of content from granules

• Fibrous structursSubmembrane filaments and mikrotubuls- they maintain the discoid shape and position of organels in

nonactive plateletsCytoplasmatic mikrofilaments- they are responsible for contraction at the releasing

granular content

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

1. Platelets –structure

Chemical substances: • Calcium ions• Mg- ions. • Adenosine triphosphate (ATP) • Adenosine diphosphate (ADP)

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

1. Platelets –structure

• 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)

1. Platelets –function

2. Blood clotting, haemocoagulationfactors

1. Vessel reactions in the place of damage

2. Platelet activitya) 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.

2. Blood clotting, haemocoagulationfactors

1. Vessel reactions in the place of damageVASOCONSTRICTION

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.

2. Platelet activity

- it consists in contact with collagen fibresthrough specific receptors on the platelet membrane (GP Ib) and with the certain binding places of the collagen molecule

a) adhesion: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

2. Blood clotting, haemocoagulationfactors

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

2. Blood clotting, haemocoagulationfactors

2. Blood clotting, haemocoagulationfactors

c) aggregation

- 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)

3. Haemocoagulation- Haemocoagulation factors

2. Blood clotting, haemocoagulation factors

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

3. Haemocoagulation

a) Intrinsic pathway b) Extrinsic pathway

2. Blood clotting, haemocoagulationfactors

3. Haemocoagulation – a) Intrinsic pathway

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

3. Haemocoagulation - Extrinsic pathway

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

3. Haemocoagulation – Polymerization of fibrinogen

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

3. Fibrinolysis

https://en.wikipedia.org/wiki/Carboxypeptidase_B2

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

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

3. Group antigens, blood transfusion

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

3. Group antigens, blood transfusion

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.

Heredity of blood groups

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)

Blood Type PathologyHemolytic 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

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-matching2. Biological examination3. In the case negative reaction, the biological

examination repeat still 2x4. After the stopping of transfusion – to monitor

pacient 2-4 hours is needed