Pathology
Wound Healing
Question 17 of 180
Which type of collagen is initially laid down in early wound healing:
Answer:
Fibroblasts migrate to the wound (about 2 - 5 days after wounding), proliferate and secrete extracellular matrix comprising mainly collagen (type III) and fibronectin to plug the gap.Stages of Wound Healing
Pathology / Wound Healing
Last Updated: 8th November 2021
The process of wound healing in the skin depends on the size of the injury; it occurs by two mechanisms.
Healing by First Intention vs Secondary Intention
Healing by first intention can occur when the wound edges are opposed, the wound is clean and uninfected and there is minimal loss of cells and tissue i.e. surgical incision wound. The wound margins are joined by fibrin deposition, which is subsequently replaced by collagen and covered by epidermal growth.
Healing by secondary intention occurs when wound margins are not opposed due to extensive tissue damage and involves the following:
- Tissue defect fills with granulation tissue
- Epithelial regeneration to cover the surface
- Granulation tissue eventually contracts resulting in scar formation; myofibroblasts within granulation tissue are attached to each other and to adjacent extracellular matrix, their contraction draws together the surrounding matrix and thus reduces the size of the defect, but in doing so produces a scar
Stages of Wound Healing
Acute wound healing has four main stages:
Haemostasis:
- Endothelial damage results in platelet adhesion, activation and aggregation with subsequent activation of the coagulation cascade and fibrin deposition.
- The blood clot seals the wound and creates a waterproof layer of fibrin and fibronectin.
- Tissue damage and microbes stimulate acute inflammation.
Inflammation:
- Infiltration of inflammatory cells (initially predominantly neutrophils but these are replaced by macrophages by day three) leads to phagocytosis of pathogens, damaged cells and debris.
- Basal epithelial cells from the edges secrete and respond to epithelial growth factor (EGF); they proliferate and migrate under the clot, adhering to fibronectin.
- Platelets secrete platelet-derived growth factor (PDGF) into the wound stimulating fibroblasts.
Proliferation:
- New blood vessels bud off nearby capillaries stimulated by VEGF; at first they are solid cords, later they develop a lumen.
- Fibroblasts migrate to the wound (about 2 - 5 days after wounding), proliferate and secrete extracellular matrix comprising mainly collagen (type 3) and fibronectin to plug the gap.
- Myofibroblasts contract, reducing the area required to heal.
- Matrix metalloproteinases secreted by fibroblasts open paths in the collagen matrix for cellular and vascular traffic and remodelling.
Remodelling:
- Type 3 collagen is resorbed and replaced by scar tissue (type 1 collagen) starting by day 5.
- Mature collagen contracts.
- Blood vessels regress.
- Further wound contraction occurs reducing the total area of scarring by 50-70%.
- Basic healing is complete by 5-10 days but maximal wound strength (80% of normal) may take 12 weeks.
Factor Affecting Healing
The following are essential for good healing:
- An adequate blood supply to deliver inflammatory cells to remove debris, and to provide nutrition and oxygen to the regenerating tissue
- Nutrients to supply building materials
- Vitamins, especially vitamin C, used in the manufacture of tropocollagen
- Immobilisation of the healing tissues
- The absence of infection or other destructive processes
- Viable cells that can undertake the process of clearing debris and replacing the damage tissue
| Local factors affecting healing | Systemic factors affecting healing |
|---|---|
| Tissue hypoxia | Malnutrition (vitamin A, vitamin C and zinc deficiency) |
| Excessive tension of wound edges | Age |
| Repeated trauma | Immunodeficiency |
| Infection | Glucocorticosteroid therapy |
| Presence of foreign material | Diabetes mellitus |
| Tissue necrosis | Smoking |
| History of irradiation | Obesity |
Complications of Healing
- Scar contractures e.g. burns or wounds over joints
- Hypertrophic scarring
- Keloid formation
- Failure to heal (abscess or empyema formation)
- Failure to unite (skin, muscle or fascia wound breakdown)
- Traumatic neuroma
- Fracture complications
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- Biochemistry
- Blood Gases
- Haematology
| Biochemistry | Normal Value |
|---|---|
| Sodium | 135 – 145 mmol/l |
| Potassium | 3.0 – 4.5 mmol/l |
| Urea | 2.5 – 7.5 mmol/l |
| Glucose | 3.5 – 5.0 mmol/l |
| Creatinine | 35 – 135 μmol/l |
| Alanine Aminotransferase (ALT) | 5 – 35 U/l |
| Gamma-glutamyl Transferase (GGT) | < 65 U/l |
| Alkaline Phosphatase (ALP) | 30 – 135 U/l |
| Aspartate Aminotransferase (AST) | < 40 U/l |
| Total Protein | 60 – 80 g/l |
| Albumin | 35 – 50 g/l |
| Globulin | 2.4 – 3.5 g/dl |
| Amylase | < 70 U/l |
| Total Bilirubin | 3 – 17 μmol/l |
| Calcium | 2.1 – 2.5 mmol/l |
| Chloride | 95 – 105 mmol/l |
| Phosphate | 0.8 – 1.4 mmol/l |
| Haematology | Normal Value |
|---|---|
| Haemoglobin | 11.5 – 16.6 g/dl |
| White Blood Cells | 4.0 – 11.0 x 109/l |
| Platelets | 150 – 450 x 109/l |
| MCV | 80 – 96 fl |
| MCHC | 32 – 36 g/dl |
| Neutrophils | 2.0 – 7.5 x 109/l |
| Lymphocytes | 1.5 – 4.0 x 109/l |
| Monocytes | 0.3 – 1.0 x 109/l |
| Eosinophils | 0.1 – 0.5 x 109/l |
| Basophils | < 0.2 x 109/l |
| Reticulocytes | < 2% |
| Haematocrit | 0.35 – 0.49 |
| Red Cell Distribution Width | 11 – 15% |
| Blood Gases | Normal Value |
|---|---|
| pH | 7.35 – 7.45 |
| pO2 | 11 – 14 kPa |
| pCO2 | 4.5 – 6.0 kPa |
| Base Excess | -2 – +2 mmol/l |
| Bicarbonate | 24 – 30 mmol/l |
| Lactate | < 2 mmol/l |
