Unit 3 - Blood PART E Flashcards
Hemostasis
Process of preventing blood loss (opposite of hemostasis is hemorrhage).
What are the 4 main steps of Hemostasis?
- Vasconstriction (vascular spasm)
- Platelet plug formation
- Coagulation (clot formation)
- Fibrinolysis (Clot dissolution)
- Vasconstriction (vascular spasm)
a. Damage to blood vessel wall activates local pain receptors. Which triggers an increase in SYMPATHETIC ACTIVITY causing vasoconstriction that reduces blood flow to the site of damage.
b. Platelets stick to exposed collagen fibers and release platelet factors (factors = ions/molecules/cytokines), some of which reinforce vasoconstriction including:
i. Serotonin
ii. Thromboxane A2
Platelets stick to exposed collagen fibers and release platelet factors (factors = ions/molecules/cytokines), some of which reinforce vasoconstriction including:
i. Serotonin (from secretory vesicles of platelets)
ii. Thromboxane A2 (from platelet membrane)
- also contribute to platelet aggregation (along with ADP & PAF)
- net result is a growing platelet plug that seals the damaged vessel wall
- Platelet Plug Formation
a. Platelet adhesion
b. Factors involved in platelet aggregation include:
i. Platelet Activating Factor (PAF).
ii. Serotonin
iii. Adenosine diphosphate(ADP)
iv. Thromboxane A2
c. Platelet plug formation cannot spread beyond the site of injury due to secretion of PROSTACYCLIN and NITRIC OXIDE (NO) from surrounding endothelial cells which blocks adhesion and aggregation.
Platelet adhesion
platelets stick to exposed collagen and release factors that attract other platelets to the site (POSITIVE FEEDBACK) that fill in damaged area forming a platelet plug.
Factors involved in platelet aggregation include:
i. PLATELET ACTIVATING FACTOR (PAF).
ii. SEROTONIN (from secretory vesicles of platelets)
iii. ADENOSINE DIPHOSPHATE (ADP) (from platelet mitochondria)
iv. THROMBOXANE A2 (from platelet phospholipids)
ii & iv are VASOCONSTRICTORS
Serotonin & Thromboxane A2 are…
VASOCONSTRICTORS
Platelet plug formation CANNOT spread beyond the site of injury due to what?
secretion of PROSTACYCLIN and NITRIC OXIDE (NO) from surrounding endothelial cells which blocks adhesion and aggregation.
Coagulation
complex process in which fluid blood forms a gelatinous clot
- Coagulation (Clot Formation)
a. Cascade/Network of factor interactions activated through two pathways almost simultaneously:
i. intrinsic Pathway (Contact Activation Pathway)
ii. Extrinsic Pathway (Cell Injury/Tissue Factor Pathway)
b. Each pathway results in activation of Factor X, whose
formation is the start of the common pathway.
c. Factor X combines with Ca2+, Factor V, and phospholipids to form PROTHROMBIN ACTIVATOR.
- Active factor X exerts positive feedback on the extrinsic pathway (activating more Factor VII and Tissue Factor III).
d. Prothrombin activator converts Prothrombin (a plasma protein) into Thrombin.
d. Thrombin acts on Fibrinogen (soluble clotting protein in plasma) to produce insoluble Fibrin polymers. These form a web of thread-like protein that covers the platelet plug and traps formed elements (RBCs).
- Thrombin exerts positive feedback on intrinsic pathway (activates more Factor XI = plasma thromboplastin)
e. ActiveFactorXIII(FibrinStabilizingFactor) converts fibrin into a cross-linked polymer, and stabilizes the clot.
Cascade/Network of factor interactions activated through two pathways almost simultaneously: (eventually merge into 1)
i. Intrinsic Pathway (Contact Activation Pathway)
- Initiated by factors in blood exposed to collagen (tissue factor XII)
ii. Extrinsic Pathway (Cell Injury/Tissue Factor Pathway)
- Initiated by factors in surrounding damaged tissues (Tissue Factor III = Tissue thromboplastin)
Intrinsic Pathway (Contact Activation Pathway)
Initiated by factors in blood exposed to collagen (tissue factor XII)
Extrinsic Pathway (Cell Injury/Tissue Factor Pathway)
Initiated by factors in surrounding damaged tissues (Tissue Factor III = Tissue thromboplastin)
Prothrombin activator converts Prothrombin (a plasma protein) into _____.
Thrombin
- the enzyme that converts FIBRINOGEN into insoluble FIBRIN polymers
- these fibrin fibers become part of the clot
Thrombin acts on ______ (soluble clotting protein in plasma) to produce insoluble Fibrin polymers. These form a web of thread-like protein that covers the platelet plug and traps formed elements (RBCs).
FIBRINOGEN
What is something to note about Coagulation (Clot Formation)?
~ 2 dozen factors involved. These are obtained from the diet, liver (plasma proteins) damaged tissue and platelets.
Vitamin K is required for synthesis of 4 of the factors (II, VII, IX, X) ,
- Fibrinolysis (Clot Dissolution)
After blood vessel wall is repaired, clot is broken up by fibrin digesting enzyme called PLASMIN.
- First, thrombin and TISSUE PLASMINOGEN ACTIVATOR (tPA) convert PLASMINOGEN in the clot into plasmin.
- Plasmin breaks up clot (fibrin) (= FIBRINOLYSIS).
- Phagocytes then remove the clot in clumps.
Plasminogen
an inactive form of plasmin
- part of the clot
Anticoagulants
Produced by the body prevent spread of clot.
Block parts of coagulation cascade. (AKA prevent coagulation from taking place)
What are the 2 mechanisms that limit the extent of blood clotting within a vessel:
(1) inhibition of platelet adhersion &
(2) inhibitation of the coagulation cascade & fibrin production
Most anticoagulants act by…
blocking 1 or more of the rxns in the coagulation cascade
Which anticoagulants does the body produce:
- Heparin
- Antithrombin III
- Protein C
The body produces these 2 anticoagulants:
- Heparin
- Antithrombin III
INHIBIT ACTIVE FACTORS IX, X, XI & XII
- work together
The body produces this anticoagulant:
3. Protein C
INHIBITS ACTIVE FACTORS V & VIII
Application of hemostasis and blood clotting (3 ex’s):
E.g.1. Thrombus = stationary clot in an undamaged vessel
(increases resistance to blood flow)
E.g2. Embolus = free floating clot
- can cause blockage of small vessels of the lungs (pulmonary embolism) or brain (cerebral embolism =
stroke) or heart (coronary embolism – leads to myocardial infarction)..
E.g.3: Hemophilia
- Clotting is abnormal or absent
- Majority of people with hemophilia are lacking clotting factor VIII (also known as Antihemophilic Factor)
Application of hemostasis and blood clotting: Thrombus
THROMBUS = stationary clot in an undamaged vessel
(increases resistance to blood flow) & stop BF
Application of hemostasis and blood clotting: Embolus
EMBOLUS = free floating clot
- can cause blockage of small vessels of the lungs (pulmonary embolism) or brain (cerebral embolism =
stroke) or heart (coronary embolism – leads to myocardial infarction).. (AKA heart attacks, occur when a coronary blood vessel is blocked by a blood clot)
Application of hemostasis and blood clotting: Hemophilia
- Clotting is abnormal or absent
- Majority of people with hemophilia are lacking clotting factor VIII (also known as Antihemophilic Factor)
(best-known coagulation disorder)
Hemophilia
a name given to several diseases in which 1 of the factors in the coagulation cascade is either DEFECTIVE or LACKING
