A & P 2 - Blood Hemostasis

Front 1

How are platelets produced and what is their lifespan and when is it highest?

Back 1

detached from megakaryocytes

production stimulated by Thrombopoetin (TPO)

8-12 day life span, destroyed in liver.

high during digestion, exercise, and pregnancy

circadian rhythm - count is higher during day than at night

Front 2

What are some structural features of platelets?

Back 2

small, rod shaped

no nucleus

permeable plasma membrane

contractile proteins are actin and myosin

contain mitochondria, have remnants of golgi and ER

Front 3

What are some blood functions of blood platelets?

Back 3

participate in hemostasis and maintaining blood vessel integrity

releases biologically active substances (ex. seratonin and thromboaxane A2) that cause vasoconstriction

release growth factors that stimulate formation of blood vessels and repair of vascular and bone leasions (ex. platelet-derived growth factor)

Front 4

What is hemostasis and what are the stages?

Back 4

arrest of bleeding from damaged blood vessels

Stages:
-local vasoconstriction
-formation of a platelet plug
-blood clotting: web of fibrin proteins that surround plug

Front 5

What is local vasoconstriction?

Back 5

Results from:
release of vasoconstrictor substance (paracrine and autocrine agents)

local myogenic spasm (initiated by direct tissue damage)

reflex vasoconstriction (activation of nocireceptors)

Effects:
-lower blood flow and pressure in damaged area
-obliteration of lumen of small blood vessels

Front 6

What are the stages of Platelet plug formation?

Back 6

Platelet Adhesion:
-damage to endothelium
-exposure of collagen fibers to blood
-platelets stick to collagen via protein bridges

Platelets release reaction:
-binding of platelets to collagen --> degranulation
-seratonin, adrenaline, thromboxane A2, and ADP

Platelet Activation:
-serotonin, adrenaline and ADP act locally --> changes in metabolism, shape, and surface proteins of platelets
-serotonin and thromboaxane A2 stimulate local vasoconstriction

Loose Platelet Aggregation:
-ADP and Thromboaxane A2 stimulate adhesion of next layers through positive feedback and formation of platelet plug inside vessel

Viscous metamorphosis, irreversible platelet aggregation:
-destruction of platelets membrane (stimulated by thrombin)

Plug Retraction:
-contraction of actin and myosin --> compression and strengthening of platelet plug

Front 7

What are factors that prevent formation of a platelet plug?

Back 7

Prostacycline (type of prostaglandin)
-inhibit platelet aggregation

NO:
-inhibits platelet adhesion, activation and aggregation and stimulates local vasodilation

Front 8

What is actual blood coagulation?

Back 8

transformation of blood into a solid gel

series of reactions in which each factor activated in turn activates the next factor

reaction: soluble protein fibrinogen --> insoluble protein fibrin

Front 9

What are some important Plasma clotting factors?

Back 9

act as enzymes or cofactors for enzymes

plasma proteins synthesized by liver (except for calcium and thromboplastin)

I: Fibrinogen - converted to fibrin
II: Prothrombin - enyzme
III: Tissue thromboplastin - cofactor
IV: Calcium ions - cofactor
V: Proecelerin - cofactor
VII: Proconvertin - enzyme
VIII: Antihemophilic factor - cofactor
IX: Christmas factor - enzyme
X: Stuart-Prower factor - enzyme
XI: Plasma Thromboplastin antecedent - enzyme
XII: Hageman factor - enzyme
XIII: Fibrin stabilizing factor - enzyme

Front 10

What are 3 phases of blood coagulation?

Back 10

formation of prothrombinase (prothrombin factor)

formation of active thrombin from prothrombin - catalyzed by prothrombin activator

formation of insoluble fibrin from soluble fibrinogen - catalyzed by thrombin

Front 11

What are the 2 pathways in Phase 1: Formation of Prothrombinase?

Back 11

Intrinsic Pathway:
-starts with trauma or blood contact with collagen
-blood contains all factors necessary for coagulation
-slow, takes 1-6 mins

Extrinsic Pathway:
-starts with traumatized vascular wall which come in contact with blood
-requires cellular element outside of blood - tissue factor (tissue thromboplastin)
-fast, 15 secs

Front 12

What happens in Phase 2: Formation of Active Thrombin?

Back 12

Thrombin:
-catalyzes formation of fibrin from fibrinogen
-contributes to activation of factors XI, VIII, and V - positive feedback
-activates factor XIII
-promotes platelet aggregation
-synthesis of prothrombin in liver requires vitamin K

Front 13

What happens in phase 3: Formation of Fibrin?

Back 13

thrombin catalyzes formation of fibrin monomers
-needs Ca and platelet factors

monomers join together to form insoluble fibrin polymers

factor XIII + Ca catalyzes formatino of covalent cross bridges which stabilizes fibrin

Front 14

What are the final events of hemostasis?

Back 14

fibrin forms meshwork

clot occludes damaged blood vessel and stops bleeding

retraction of clot due to contraction of fibrin fibers and contractile proteins of platelets

Front 15

What is the role of vitamin K in clotting?

Back 15

required for hepatic synthesis of prothrombin and factors VII, IX, X

deficiency:
results from:
-low dietary intake
-low intestinal absorption of fats due to low bile secretion

leads to:
-bleeding tendency

Front 16

What is the role of Ca in coagulation?

Back 16

Calcium is required for all steps of coagulation (except first 2 steps of extrnisic pathway)

-low calcium level lead to low blood clotting of both pathways

Front 17

What is the role of platelets in coagulation?

Back 17

activated platelets:
-bind to several clotting factors
-display phospholipids (platelet factors) which act as cofactors

Front 18

What is the role of the liver in blood coagulation?

Back 18

synthesis of plasma clotting factors

synthesis of bile salts which are required for intestinal absorption of lipid soluble vitamin K

Front 19

What are some anticlotting mechanisms?

Back 19

factors that reduce adhesiveness of platelets:
-smooth lining of intact vessel walls
-muopolysaccharides (glycocalyx) - repulsion of clotting factors and platelets
-circulation of blood
-protacyclin: antiplatelet-aggregation effect by intact endothelial cells

Front 20

What are some Natural Anticoagulants?

Back 20

Tissue factor pathway inhibitor:
-secreted by endothelial cells
-binds to tissue thromboplastin complex and inhibits activation of factor X --> less thrombin production in external pathway

Fibrin:
-absorbs 85-90 % of thrombin

Antithrombin III (antithrombin-heparin cofactors)
-is a plasma alpha globulin
-activated when it binds to heparin
-inactivates thrombin and factors IX, X, XI, XII

Heparin:
-produced by mast cells and basophils
-facilitates binding of antithrombin III and thrombin

Activated protein C:
-inactivates factors Va and VIIIa and activates plasminogen

Front 21

What are some drugs that inhibit blood clotting?

Back 21

Heparin

Coumarin derivates (ex. warfarin):
-blocks effect of vitamin K

Aspirin:
-inhibits prostaglandins and thrombaxanes synthesis --> inhibition of platelet release reaction and platelet aggregation
-prevents heart attack

Front 22

What are some in vitro inhibitions of blood clotting?

Back 22

keeping of blood in siliconized containers

substances that bind ionized calcium to produce un-ionized calcium compound or to form insoluble salts with calcium
-sodium citrate or oxalate
-ammonium or potassium citrate

Heparin

Front 23

What is the Fibrinolytic system?

Back 23

Fibrinolysis is the dissolution of blood clots

fibrin is digested by an enzyme plasmin

in blood, plasmin is present as inactive precursor, plasminogen

plasminogen is activated by plasminogen activators
-Tissue plasminogen activators (t-PAs): secreted by endothelial cells

Front 24

What are the two types of abnormalities of hemostasis?

Back 24

excessive bleeding - caused by deficiency of clotting factors

excessive clotting - thrombosis and embolism

Front 25

What are conditions that cause excessive bleeding?

Back 25

vitamin K deficiency

deficiency of clotting factors (hemophilia)

deficiency of thromboytes - thromocytopenia

Front 26

What is hemophilia?

Back 26

a hemorrhagic disease which results from deficiency of:
-Factor VIII - hemophilia A or classical
-Factor IX - hemophilia B, Christmas disease
-Factor XI - hemophilia C

is a genetic disease:
-Hemophilia A and B are sex linked (X Chromosome)
-usually occurs in males
-females are carriers

Front 27

What is Intravascular Clotting?

Back 27

Thrombosis - spontaneous blood clotting within the CVS, attached to site of origin

Embolus - blood clot detached from site of origin

Common Causes:
-roughened endothelial surface (ex. atherosclerosis)
-slow blood flow
-large areas of necrotic tissue

Consequences:
-low hemodynamics in affected area

Thrombolytic drugs:
-chemical substances that dissolve blood clots
-directly or indirectly activates plasminogen