Wound healing / Flashcards

1
Q

What is a wound, causes and consequences?

A

Any disruption to the integrity of skin, mucosal surfaces or organ tissue
Causes: accidental or intentional (surgery) aetiology, part of a disease process
Consequences: coordinated sequence of cellular and non-cellular processes to restore tissue - haemostasis, inflammation, proliferation, remodelling/maturation

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2
Q

What are acute wounds and causes?

A

Acute wounds occur suddenly
Acute wounds affecting soft tissue, usually pass through healing phases quickly
Usually caused by trauma

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3
Q

What will abnormal wound healing lead to?

A

Increased patient morbidity and mortality
Poor cosmetic outcome
Health economic outcomes
Psychological sequelae for the patients

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4
Q

What are the different types of wound closure in soft tissue?

A

Closure by primary intention:
Deliberate closure of a small wound, edges are aligned
Closure by secondary intention:
extensive tissue loss, no deliberate closure. Repair prolonged, much granulation tissue
Tertiary intention healing:
Intentional delay of wound healing due to decontamination, risk of infection. Closure performed after interventions

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5
Q

What are the events leading up to haemostasis?

A

Vascular injury
Damaged arterioles rapidly constrict by smooth muscle contraction - triggered by SNS and vasoconstrictors released locally (thromboxane A2 and endothelin)
Vessels up to 5mm can close just by contraction if transverse wound
Reduced BF leads to tissue hypoxia and acidosis which promotes production of vasoactive metabolites e.g. NO, adenosine
>vasodilation and relaxation of the arterial vessels
Coagulation is then needed

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6
Q

What occurs in the early stages of inflammation?

A

Mast cells release histamine
Increases vasodilation and increases vascular permeability
Entry of inflammatory cells into the wound
Complement is activated
Neutrophils infiltrate wound and carry out phagocytosis, degranulation and NETosis over first 48 hours

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7
Q

What occurs in late stage inflammation with macrophages?

A

Macrophages are pro-inflammatory in the first days - M1 phenotype
Become anti-inflammatory/more pro-resolution later - M2 phenotype
Macrophages release collagenases (MMPs 1, 8 & 13) - break down collagen and allow remodelling
Macrophages release PDGF which recruits fibroblasts and FGF stimulates them to migrate and proliferate
Release TGF-B - stimulates fibroblasts to secrete collagen
Release VEGF stimulates endothelial cells to proliferate >granulation tissue

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8
Q

What occurs in late stage inflammation with other cells than macrophages?

A

Lymphocytes appear in wound ~72hrs and regulate healing, Persist until healed
Dendritic epidermal T cells secret keratinocyte GF (stimulate keratinocyte prolif) and IGF-1 (differentiation)
Products of arachidonic acid metabolism have anti-inflam properties which dampen immune response and allow next phase

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9
Q

What processes occur during proliferation phase?

A

Angiogenesis
Formation of granulation tissue
Fibroblast migration
Collagen deposition
Epithelialisation
Wound contraction

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10
Q

What stimulates and drives angiogenesis?

A

Triggered from formation of haemostatic plug; platelets release VEGF (and TGF-B, PDGF and FGF)
Hypoxia drives it. VSGF secreted by macrophages, fibroblasts and others
Stimulate endothelial cell proliferation and migration to form tubes
MMPs are important for remodelling of the ECM

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11
Q

What happens during fibroblast proliferation and migration stage of proliferative stage in wound healing?

A
  • Wound rich in fibroblasts that proliferate and migrate in response to growth factors
  • TGF-B stimulates fibroblasts to lay down ECM proteins (collagen, fibronectins, proteoglycans)
  • Fibroblasts release MMPs - collagenases MMPs 1, 8, 13
  • Collagens synthesised by fibroblasts provide strength to tissues
  • Fibroblasts then change to myofibroblast phenotype and connect to surrounding cells and ECM proteins
  • Scar formation
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12
Q

What happens in the re-epithelialisation stage of proliferation?

A

Cytokines and growth factors at the wound site stimulate basal epithelial cells at wound edge to migrate across the wound bed by EMT
Basal epithelial cells adhere to deposited ECM
Epithelial cells proliferate, differentiate and stratify to repopulate epithelial cell levels
If the wound area is large contraction of the wound is required

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13
Q

What occurs during wound contraction in proliferation contraction?

A

Mediated mainly by myofibroblasts
Cell bodies are pulled closer together decreasing the area of tissue needing to heal

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14
Q

Remodelling phase of wound healing

A

Balance between synthesis and degradation of collagen and other proteins which become increasingly well organised
Wounds never achieve the same level of tissue strength
> Normal epithelium and maturation of scar tissue
As scar matures, level of vascularity decreases and scar changes from pink to grey with time
Influenced by wound size, shape and location

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15
Q

What are chronic wounds?

A

Soft tissue wounds that have not healed within 12 weeks after insult

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16
Q

What are the stages of bone healing?

A

Haemostasis
Inflammation
Proliferation - soft callus formation and woven bone
Maturation/remodelling

17
Q

What is the first stage of bone fracture healing?

A

Haematoma forms
Stabilises fracture, provides matrix for infiltrating cells, source of signalling molecules to initiate inflammation
Coagulates between and around bone ends

18
Q

What is the second stage of bone fracture healing?

A

Inflammation is initiated at the fracture site and lasts for a few days
Vasodilation and increased vascular permeability
Influx of inflammatory cells and non-cellular factors: removal of debris, drives repair process forward
Formation of granulation tissue - blood vessels, fibroblasts, new ECM
Osteoprogenitor cells recruited to site (mesenchymal cells)

19
Q

What is the third stage of bone fracture healing?

A

Soft callus formation that gives bone a stable structure
- is cartilaginous,
- bridges fracture ends
Chondrocytes lay down cartilage
Capillaries and supporting blood vessels connect in the callus
Soft cartilagenous callus then reabsorbed and replaced by hard callus - woven bone
Cartilage matrix progressively calcified and reabsorbed and replaced with bone - osteoblastic and osteoclastic activity proceeding

20
Q

What is the final stage of bone fracture healing?

A

Remodelling of callus
Woven bone is reabsorbed and remodelled into lamellar bone
Osteoclasts resorb woven bone
Osteoblast deposition of new lamellar bone
Bone marrow restoration
Mechanical stress important for this phase