4 phases of wound healing
haemostasis
inflammatory
proliferative
remodelling
haemostasis
tissue injury -> clotting cascade -> platelet aggregation -> clot formation
platelet granules also release growth factors which initiate wound healing cascade
inflammatory mediators
histamine
serotonin
bradykinin
complement proteins
inflammatory phase wound healing
neutrophils migrate after few hours -> 4 days
clean up wound
monocytes migrate in 48-72hrs -> macrophages - promote and co-ordinate later stages of repair
proliferative wound healing phase
36hrs-2wks
fibroblasts appear between 2-4days, lay down new extra-cellular matrix -> granulation tissue
angiogenesis and epithelialisation - basal epidermal cells divide and migrate across new ECM
fracture healing - reactive phase
0-7days platelet migration and haematoma formation
acute inflammation, fibroblast migration, granulation tissue formation
remodelling phase
wound closed over
turnover of granulation tissue - matrix remodelling
fibroblasts, macrophages and granulocytes
myofibroblasts promote wound contraction
final product is an avascular acellular scar
fracture healing - soft callus phase
4d-3w
chondroblasts and fibroblasts migrate to granulation tissue -> hyaline cartilage
osteoblasts lay down weak done = woven
hyaline cartilage and woven bone form initial callus - loosely unites bone
fracture healing - hard callus
1-3m
osteoblasts differentiate from periosteum
lay down woven and trabecular bone -> hard callus
radiologically visible at 6 weeks
fracture healing - remodelling phase
osteoclasts and osteoblasts remodel bone close to original shape
trabecular bone replaced with stronger compact bone
tendon healing
fibroblasts produce type III collagen within 1st week (disorganised), large amounts by 3 weeks
gradually remodelled to type I over 18m
neuropraxia
pressure on axon, distal part has temporary damage
fully recover
axonotmesis
axon damaged but surrounding tissue intact
nerve can regenerate up to 2cm/month
neurotmesis
neural integrity lost
recovery limited
can improve with surgical repair
cardiac muscle damage
necrotic muscle invaded by granulation tissue and fibroblasts, replaced by scar tissye
brain tissue damage
no fibroblasts in brain
necrotic area removed by gliosis, volume of brain lost
neuroplasticity allows some regain of function
chronic wounds - factors
infection
ischaemia
oedema
underperfusion
hypoxia
further tissue damage
lack of nutrients
inflammation
biological response of vascular tissues to harmful stimuli
deal with cause
remove damage
initiate healing
inflammation - initial stages
macrophages - release TNFa
mast cells - release histamine
act on endothelium which release prostacyclin and NO -> vasodilatation and effect junction between endothelial cells
neutrophils migrate towards endothelial surface and attach to surface -> release prostaglandins and interleukins
gaps created between endothelial cells -> migration of neutrophils into tissues
ILs attract more cells
Acute phase response
tissue damage -> neutrophils+macrophages
cytokines -> IL-6, IL-1 and TNFa
adrenal/pit axes -> ACTH -> steroids
induces prostaglandins -> hypothalamus -> febrile response
liver biosynthesis -> acute phase proteins -> CRP, serum amyloid
complement cascade
classical pathway IgG-antigen complexes
alternative pathway C3b
lectin pathway
amplification at each stage
lysis of bacteria
chemotactic for leucocytes
opsonisation
inflammation
kinin-kallikrein system
tissue injury -> kallikrein production
kallikrein converts kininogen -> bradykinin
bradykinin converted to inactive kinins by ACE in lungs (inhibition of pathway causes cough)
B1 receptors - pain + mitogenesis
B2 receptors - vasodilatation, increased capillary permability
prostaglandins and eicosanoids
lipids
leukotrienes
- produced in leucocytes from arachidonic acid
- inflammation
- LTD4 important in smooth muscle contraction, overproduced in asthma and allergic rhinitis
prostaglandins - produced by COX-1 and COX-2
thromboxanes - produced by activated platelets, promote aggregation and vasoconstriction
prostacyclins - released by vascular endothelium, vasodilator, inhibit platelet aggregation
hypersensitivity type I
anaphylaxis
IgE mediated
antigen reacts with IgE antibody on sensitised mast cells -> histamine and vasoactive substance release
anaphylatoid reaction similar but no preformed IgE
