blood 3 Flashcards
thrombopoiesis (generation of platelets)
liver hormone thrombopoietin stimulates megakaryocyte prod. in BM
Cell fragments = platelets break off from megakaryocytes
- Occurs in BM or quickly following entry into circulation
Megakaryocytes mature -> granules form in cytoplasm -> pieces fragment off w granules
Platelet characteristics
disc shaped
no nucl
2-3um diameter (smaller than RBCs)
pseudopodia => shape alteration
short lifespan
Contains:
- alpha granules
- dense granules
alpha granules
contain coagulation factors, pro-coagulants, platelet-dervied growth factor, adhesion molec
dense granules
contain adp, atp, ca2+, serotonin: causing vasoconstriction (less blood flow at injury)
Response to injury
- Vasoconstriction
- platelet plug (primary hemostasis)
- might be enough for small injury
- clot formation (secondary hemostasis)
hemostatic vasoconstriction
very quick upon injury
1. local contractile response (vasoconstriction and incr tissue pressure)
- Reduce diameter of blood vessels:
- Neurogenic spasm: rapid but short lasting response (1 min) - autonomic nervous system, reflex
- myogenic spasm: longer lasting response (20-30 mins) - reduced atp, leads to spasm in muscle
2. release of humoral substance
- serotonin: released from platelets
- Endothelins: released from injured endothelium
- S&E contribute to vasoconstriction
- clotting factors: blood coagulation cascade
activated platelets
Increased platelet TXA2 production (inhibits lowering of calcium) -> reduced ca2+ efflux due to low cytosolic cAMP (high cytosolic Ca2+)
resting platelets
maintain active Ca2+ efflux (low cytosolic Ca2+)
TXA2
Acts to potentiate platelet aggregation in damaged vessels, and as a …
prostacyclin
prod by endothelial cells, inhibits platelet aggregation in intact vessels (promotes inhibition pathway of calcium -> low calcium in platelets/resting state)
High cAMP levels reduce free calcium -> prevents aggregation and adhesion
COX-1
in prostacyclin and TXA2 pathways
COX-2
in prostacyclin pathway
coagulation cascade
Aim: create clot to strengthen platelet plug and complete seal
Requires thrombin - acts on fibrinogen (factor I) -> promotes fibrin clot formation
- Production dependent on:
- Extrinsic Xase (injury to vessel: activates extr first, leads to activation of intr)
- Intrinsic Xase (if there is foreign object in blood)
- Prothrombinase
Coagulation is localized thru intracate amplification network and - feedback loops
Extrinsic pathway
Initial response to vessel injury
- Tissue factor exposed to endothelial cells
- Plasma factor VII binds to TF -> converted to VIIa
- TF-VIIa complex binds Ca2+ and converts X->Xa
- TF-VIIa-Ca2+ complex (Xase) converts small amt of prothrombin -> thrombin - ensures propagation of cascade
Intrinsic pathway
Extrinsic Xase complex activates factors iX and XI
- Small amt of thrombin converts V->Va and VIII->VIIIa
- Intrinsic Xase (IXa-VIIIa-Ca2+) converts X->Xa, incombination w Va and Ca2+, activates prothrombinase (…)
common pathway
fibrinogen hydrolyzed by thrombin into fibrin monomers, monomers spon polymerize into fibrin polymers
Thrombin converts XIII to XIIIa, catalyzes formation of cross-linked lattice with covalent cross-bridging (stable fibrin)
fibrinolysis (clot breakdown)
tissue plasminogen activator (t-PA) released from endothelial tissues, binds to fibrin
If tissue is not ready to be exposed: release PAI-1 (plasminogen activator inhibitor) to stop breakdown
- t-PA converts clot-bound plasminogen -> plasmin, facilitates breakdown of stable fibrin -> soluble fragment
thrombin in hemostasis
most thrombin activation mediated by prothrombinase (common pw)
- Small amts of thrmbin activation mediated by
- thromboplastin (TF) from exposed …
- Extrinsic Xase
anticoagulation
Physical factors:
- smooth lining, (-) charge of vessels minimizes platelet adhesion
Vsodilators:
- NO incr blood flow preventing platelet activation
- PGI2 reduces platelet adhesion + aggregation
Endogenous enticoagulants
- Antithrombin III (inh IXa and Xa), …
Exogenous anticoagulants
- Heparin (prevents coagulation by stim ATIII), Ca2+ chelators (EDTA, oxalate, citrate, used in blood collection)
Platelet abnormalities
- Thrombocytopenia - platelet deficiency
- THrombocytosis - excess platelets
Hyperfibrinolysis
PA-1 deficiency
Coagulation defects
- Vit K deficiency
- Vit K req for synth of many clotting factors (prothrombin
- Hemophilia: inherited deficiency of specific coagulation factors
- Type A: factor VIII
- Type B: IX
