Nerves

1
Nerves
Smooth muscle
Red cells
Platelets
White cells eg neutrophils
Endothelium
2

• Thrombosis and haemostasis
• Platelet adhesion, aggregation, release
• Coagulation thrombin
• Local vasoconstriction
• Balance of stimulatory/inhibitory mediators
• Haemostasis trigger tissue damage
• Thrombosis trigger plaque rupture?
• Interactions between
• platelets
• coagulation cascade
• endothelial cells
• vascular smooth muscle (neuronal control too)

3
Activated platelet
Resting platelet
4
What do platelets do when they are
activated? Adhere to eg vessel wall Change shape
from disc to spiny sphere Expose fibrinogen
receptors at their surface Expose PF3 at their
surface Synthesise lipid-derived mediators (TXA2,
PGD2, PAF) Synthesise nitric oxide (NO) Release
the contents of their dense granules (5-HT, ADP,
ATP) Release the contents of their alpha granules
(proteins including PF4, fibrinogen, vWF,
PDGF) Starts within seconds, finished within a
couple of minutes
5
PLATELET RESPONSESShape change, aggregation,
release
ADP or other aggregating agents
Fibrinogen Ca2
Exposure of PF3 (procoagulant phospholipids)
Release of a granule contents
Thrombin
Release of soluble mediators
Blood clotting
6
Intrinsic pathway (in vitro contact)
Extrinsic pathway (tissue damage)
Ca2, PF3
Ca2, PF3
Xa
X
Ca2, PF3
II Prothrombin
IIa Thrombin
XIII
Ca2
Fibrinogen
Fibrin
Ca2
XIIIa
Stabilised fibrin
Binds to activated platelets
Blood clot
7

• Platelet activation
• Platelet activation involves an increase in
  cytoplasmic Ca2
• Platelets are stimulated by proteins
• collagen - subendothelial surface
• thrombin coagulation cascade
• And by small molecules
• ADP/ATP from damaged cells and platelets
• PGH2/TXA2 from platelets
• PAF from platelets
• 5-HT from platelets
• adrenaline/NA - circulating hormones

8

• Platelet inhibition
• Platelet inhibition involves an increase in
  cytoplasmic cyclic nucleotides (cAMP or cGMP)
• Platelets are inhibited by
• PGI2 from endothelium
• PGD2 from platelets
• adenosine released by hypoxic cells, formed
  during ADP/ATP degradation
• NO from platelets and endothelium

9

• Platelet mediators
• Platelets release soluble compounds that affect
  nearby cells
• Stimulatory mediators
• ADP/ATP stored in vesicles
• 5-HT stored in vesicles
• PGH2/TXA2 - synthesised
• PAF - synthesised
• Inhibitory mediators
• NO - synthesised
• PGD2 - synthesised
• As a general rule
• things that activate platelets also constrict
  blood vessels
• things that inhibit platelets also relax blood
  vessels

10
Platelet-vessel wall interactions Interactions
between platelets and the vessel wall determine
the final outcome of an initial small
aggregation The endothelium is important in
determining whether or not platelet aggregation
will spread or be reversed Healthy intact
endothelium will respond by releasing factors
that inhibit aggregation and cause vasodilation
PGI2 and NO If the endothelium is damaged
aggregation and vasoconstriction will dominate -
THROMBOSIS
11
Healthy endothelium platelets will not
aggregate, blood vessel will relax
12
Damaged endothelium platelets will aggregate,
blood vessel will contract