blood 3

Question 1

thrombopoiesis (generation of platelets)

Answer 1

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

Question 2

Platelet characteristics

Answer 2

disc shaped
no nucl
2-3um diameter (smaller than RBCs)
pseudopodia => shape alteration
short lifespan
Contains:
- alpha granules
- dense granules

Question 3

alpha granules

Answer 3

contain coagulation factors, pro-coagulants, platelet-dervied growth factor, adhesion molec

Question 4

dense granules

Answer 4

contain adp, atp, ca2+, serotonin: causing vasoconstriction (less blood flow at injury)

Question 5

Response to injury

Answer 5

1. Vasoconstriction
2. platelet plug (primary hemostasis)
   
   • might be enough for small injury
3. clot formation (secondary hemostasis)

Question 6

hemostatic vasoconstriction

Answer 6

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

Question 7

activated platelets

Answer 7

Increased platelet TXA2 production (inhibits lowering of calcium) -> reduced ca2+ efflux due to low cytosolic cAMP (high cytosolic Ca2+)

Question 8

resting platelets

Answer 8

maintain active Ca2+ efflux (low cytosolic Ca2+)

Question 9

TXA2

Answer 9

Acts to potentiate platelet aggregation in damaged vessels, and as a …

Question 10

prostacyclin

Answer 10

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

Question 11

COX-1

Answer 11

in prostacyclin and TXA2 pathways

Question 12

COX-2

Answer 12

in prostacyclin pathway

Question 13

coagulation cascade

Answer 13

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

Question 14

Extrinsic pathway

Answer 14

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

Question 15

Intrinsic pathway

Answer 15

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 (…)

Question 16

common pathway

Answer 16

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)

Question 17

fibrinolysis (clot breakdown)

Answer 17

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

Question 18

thrombin in hemostasis

Answer 18

most thrombin activation mediated by prothrombinase (common pw)
- Small amts of thrmbin activation mediated by
- thromboplastin (TF) from exposed …
- Extrinsic Xase

Question 19

anticoagulation

Answer 19

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)

Question 20

Platelet abnormalities

Answer 20

• Thrombocytopenia - platelet deficiency
• THrombocytosis - excess platelets

Question 21

Hyperfibrinolysis

Answer 21

PA-1 deficiency

Question 22

Coagulation defects

Answer 22

• 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