Normal Haemostasis

Endothelium

Antithrombotic- Anti-platelets (PGI2,NO)- Anticoagulant (ATIII, Heparin-like molecules)- Fibrinolytic (t-PA)Prothrombotic- Platelet Effects (Collagen, vWF)- Procoagulant effects (Tissue Factor)- Antifibrolytic Effects (Plasminogen inacitivators)

PlateletsAlpha granules: fibrinogen, factors V & VIII, platelet factor 4 (heparin –

binding chemokine), PDGFDelta granules: ADP, Ca2+, adrenaline/epinephrine

Role in haemostasis: adhesion -> activation/secretion -> aggregation

Coagulation CascadeProcoagulation

Extrinsic – Tissue factor, VIIIntrinsic – XII, XI, IX, VIIICommon – X, V, II, fibrinogen

Anticoagulation- antithrombins - protein c & S- Tissue factor plasminogen activator- Plasmin, fibrin split products

ThrombosisVirchow’s TriangleEndothelial injuryAlterations in Normal Blood FlowHypercoagulability

Clinical ConsequencesArterialCoolPulselessPalePainfulVenous

EmbolismPulmonary- Breathlessness

SystemicFat & MarrowAir: Decompression SicknessAmniotic

InfarctionMechanism: thrombus, embolus, compression, vasospasmMorphology

- Red infarcts- White infarcts

Histological Pattern- Coagulative- Liquefactive

Outcomes:Nature of vascular supply, rate of occlusion, tissue vulnerability, oxygen contentIf an organ has dual blood supply there tends to be haemorrhagic infarction

General Principles: V ascular Response to injury Endothelial activationDefinition: intact endothelial cells responding to various pathophysiologic stimuli by adjusting their functions or expressing newly acquired propertiesCauses: Immune/infections, haemodynamic stress, metabolic

Endothelial dysfunction

DisordersPetechiaHeparin induced thrombocytopenia

ShockClassifications

- Pathogenic (cardiogenic, hypovoaemic, septic)- Clinical (Low output, vasodilation)

Mechanism- Septic- Anaphylactic (BPT: Immune-mediated disorders)

Stages

Other random notesBradykinin – Potentiates pain, vasodilates, broken down by ACES4 – stiff myocardium (atria has to contract