bleed first harvest later
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„Blut ist ein ganz besonderer Saft!"
Mephisto in Faust
Goethe 1808
Früher wurde das Blut als Sitz der Seele und des Lebens angesehen.
Blood
Blood Components
Human blood consists of 22% solids and 78% water. Its different components are plasma (with all the different blood cells), fat globules, chemical substances (proteins, carbohydrates, hormones, etc.) and gases (oxygen, nitrogen, carbondioxide, etc.)
circulation
spleen
Destruction/removal(spleen, liver)
Production(bone marrow)
platelet countthrombopoietin
70%
30%
Platelets
When an injury occurs,
platelets attach to the
connecting tissue.
The platelets form a loose
plug and are activated by
thrombin.
Thrombin converts
fibrinogen into fibrin.
The Healing Process: The Role of Platelets
A fibrin matrix is formed, which finally results in a blood clot.
Platelets are releasing growth factors and cytokines
The Healing Process: The Role of Platelets
• Haemostasis– Primary haemostasis– Secundary haemostasis (coagulation)
• Inflammation• Antimicrobial host defence• Wound and/or bone healing, through the
release of growth factors and other mediators
Platelet Functions
+ Thrombin activation
Platelets in rest
Platelets activated
Activation of Platelets: Release of Growth Factors and Cytokines
• PDGF-AA,BB, AB• TGF-1, 2• VEGF• EGF• bFGF• IGF-I• PD-ECGF• HGF• Osteocalcin• Fibronectin• Fibrinogen• Platelet Factor 4• P-Selectin• Ca2+
• Connective-tissue activating peptide III
• Lipoxygenases• Antiplasmin• Histamine• EPEA• LMW-EMA• HMA-EMA• 12-HETE, 15-HETE• PGE1, PGE2, PGA2, PGJ2, PGF1a,
PGF2a• Serotonin• ADP
Growth Factors and Cytokines in Platelets and White Blood Cells
Role of Growth Factors
• PDGF– Stimulates cell replication– Promotes angiogenesis– Promotes epithelialisation– Promotes granulation tissue formation
• TGF– Promotes formation of extracellulair matrix– Regulates bone cell metabolism
• VEGF– Promotes angiogenesis
• EGF– Promotes cell differentiation– Stimulates re-epithelialisation, angiogenesis and collagenase
activity• FGF
– Stimulation of angiogenesis– Promotes proliferation of endothelial cells
and fibroblasts
• Serotonin– Vasoconstriction, increased capillary permeability
• PDGF– Chemotaxis, vasoconstriction, SMC proliferion,
activation of monocytes and neutrophils• -TG
– Neurophil recruitment• TGF-
– Chemotaxis, inhibits neutrophil apoptosis, fibroblast proliferation
Role of Inflammatory mediators
• Toxic O2 metabolites (e.g. O2-, H2O2, OH-)
– All are potent antimicrobial activity
• Antimicrobial peptides (e.g. PF4, PBP, CTAP-3, NAP-2, RANTES, TB-4, FPA, FPB)
• Chemotactic receptors (e.g. C3a, CCR, C5a, thrombocidins)– Involved in guiding platelets towards sites of microbial infection
– Platelets are the first cells to arrive at a site of infection!
Role of Antimicrobial Proteins in Host Defence
Haemostasis 1 d Coagulation CascadeFibrin Matrix Formation
PDGFFGFTGF
Inflammation 1- 4 d Leuco’s macrophage infiltrationIncreased vasodilatation & permeability
TGF FGFPDGF IL-1EGF TxA2
Proliferation 4 d – 3 wk Matrix productionNeovascularizationEpithelialization
FGF TGFPDGF EGF PDAF
Remodelling 3 wk – 2yr Collagen deposition – degradationStable scar formation
TGF PDGFFGF TIMP
Role of Growth Factors in Wound Healing
• Vascularisation: VEGF and bFGF– Asahara et al. Circulation. 92:365. 1995.
• Migration: PDGF and TGF- – Lind M. Acta Orthop. Scand. Supp. 283:2. 1998.
• Proliferation: PDGF, TGF-, and EGF– Slater et al. J. Orthop. Res. 13(5):655. 1995.
• Differentiation: FGF, TGF-, and IGF – Kasperk et al. Growth Factors. 3:147. 1990.
Synergistic Action of Growth Factors
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