Wound Healing

Question 1

Epidermis

Answer 1

External surface of skin consisting of keratinised squamous epithelium

Question 2

Dermis

Answer 2

Dense fibroelastic connective tissue with rich vascular and sensory receptors

Question 3

Hypodermis

Answer 3

Also subcutaneous layer containing adipose tissue

Question 4

Pathophysiology of wound healing

Answer 4

1) Acute inflammatory phase
2) Proliferative phase
3) Maturation phase

Question 5

1) Tissue injury

Answer 5

Platelet activation
Clot formation
Complement activation
ACUTE INFLAMMATORY PHASE

Question 6

2) Acute inflammatory phase

Answer 6

Vasodilation
Vascular permeability
Influx of fibroblasts and neutrophils
Release of cytokines and growth factor
PROLIFERATION PHASE

Question 7

3) Proliferation phase

Answer 7

Fibroblasts 4-5 days ECM deposition)
Endothelial cells (Angiogenesis is triggered simultaneously as fibroblast activation, matrix metalloproteinases require zinc and ia proteolysis allow endothelial cell passage)
Keratinocytes/epithelial cells (wound closure usually within 48hrs)

Question 8

3b) Proliferation phase

Answer 8

Epithelialisation
Angiogenesis
Collagen synthesis
Wound healing, maturation phase and remodelling

Question 9

Cell types and timing

Answer 9

Platelets....immeddaysiate
Neutrophils...0-1 day
Macrophages...1-2 days
Fibroblasts...2-4 days
myofibroblasts...2-4 days
Endothelial cells...3-5 days

Question 10

Maturation and remodelling phase

Answer 10

Reduced vasculature causing change in scar colour

Tensile strength change as triple alpha helix collagen forms fibrils and cross links become stronger (aided by vit C)

Question 11

Wound strength

Answer 11

Strength initially increases vquickly first 7-10days
Wounds usually take up to 12-18months to regain full maturation
Bowel and muscle-1 month
Skin-6 months

Question 12

Wound healing types

Answer 12

Primary intention
Secondary intention
Tertiary intention

Question 13

Bone and callus Primary healing

Answer 13

Primary bone healing occurs if fracture gap is 1-2mm, stabilised and anatomically reduced with good stable blood supply. This allows Haversian remodelling to occur and no callus formation

Question 14

Bone and callus Secondary healing: Haematoma

Answer 14

Haematoma formation: Rupture of blood vessels within the medullary cavity, haematoma fills the fracture gap and surrounding tissues
Haematoma walls off fracture site and fills it with an influx of inflammatory cells, fibroblasts and capillary vessels

Question 15

Bone and callus Secondary healing: Inflammatory Phase

Answer 15

Necrotic areas of fracture release inflammatory markers promoting neutrophil chemotaxis
Neutrophils release cytokines including TGF-b and fibroblast growth factor activating osteoprogenitor cells

Question 16

Bone and callus Secondary healing: Repair Phase

Answer 16

Post 1 week haematoma–>soft callus
Soft callus–>fibrous matrix
Fibrous matrix–>cartilaginous phase–>bony callus
Hard callus is formed by osteoblasts placing woven bone beneath periosteum

Question 17

Bone and callus Secondary healing: Remodelling Phase

Answer 17

Remodelling takes place over months and years following a fracture.
Haversian remodelling replaces disordered callus with lamellar bone (more organised)
Wolff’s law dictates internal architecture of bone alters in response to the varying loads placed upon it

Question 18

Wound healing in Tendon, Nerve

Upper limb fracture, Lower limb fracture

Answer 18

Tendon: 3-5 weeks partial mobility, 5-12 full mobility, >12 full strength
Nerve: 4-6 weeks cast immobilisation of joint above/below, >6 weeks to free mobility

Upper limb fracture: 3-4weeks in cast
Lower limb fracture: 6-8 weeks, 3/4wks protected weight bearing, 12-16wks full wt bearing

Question 19

Nerve injury overview (III)

Answer 19

Neuropraxia (I)-No axonal injury
Axonotmesis (II)-Axonal injury but preservation of the support framework
Neurotmesis(III-V)-Support framework lost

Question 20

Principles of nerve repair

Answer 20

1) Apposition of nerve ends
2) Healthy tissue surrounding
3) No tension
4) Minimal dissection

Question 21

Neuropraxia

Answer 21

Mildest form of injury
Crush, contusion or stretch
The axon is preserved but there is a loss or reduction of signal along a segment of the nerve causing a temporary loss of function (hrs-months) average recovery is 6-8weeks.
Motor>Sensory>Autonomic

Question 22

Axonotmesis

Answer 22

Axonal disruption with preservation of the epineurium and perineurium. Wallerian degeneration occurs at the distal axon (anterograde) with a degree of retrograde degeneration of the remaining proximal axon.

Recovery occurs along the preserved framework, the proximal axon regenerates 2-3mm with the distal recovering 1mm per day. Recovery is slow taking weeks-months

Question 23

Neurotmesis

Answer 23

Grade 3-5
Severity ranges up to complete transection of the axon but often involves internal disruption of the epi-,peri- and endo-neurium. Neuroma occurs at the proximal stump of the nerve
III-Endoneurium
IV-Perineurium
V-Epineurium

Question 24

Hepatocyte Regeneration

Answer 24

Initiation-TNF-a and IL-6
Sustained-HGF and TGF-b
Termination-TGF-b1

Question 25

Delayed wound healing (nutritional factors)

Answer 25

Protein-ECM and immune response
Vitamin A-Epithelial cell proliferation and differentiation
Vitamin B6-Collagen cross-linking
Vitamin C-Hydroxylation of proline and lysine. Hydroxyproline-transports collage out of cells. hydroxylysine allows collagen cross linking
Zinc-Metalloproteinases
Copper-Collagen to elastin cross linking