Pathophysiology of Diabetic Foot Ulcers
Primary Pathophysiological Mechanisms
- Diabetic peripheral neuropathy plays a central role in the development of diabetic foot ulcers, alongside peripheral arterial disease, foot deformities, and abnormal biomechanical loading of the foot, according to the American Diabetes Association 1, 2
- Neuropathy leads to an insensitive and sometimes deformed foot, causing abnormal walking patterns, as reported by the American Diabetes Association 1
- Loss of protective sensation allows minor trauma to go unnoticed, precipitating ulceration, as noted by the American Diabetes Association 2
- Motor neuropathy contributes to foot deformities such as claw toes and hammer toes, creating areas of high pressure, according to the American Diabetes Association 3
- Autonomic neuropathy reduces sweating, leading to dry skin prone to cracking, as reported by the American Diabetes Association 4
Biomechanical Abnormalities
- Loss of sensation, foot deformities, and limited joint mobility result in abnormal biomechanical loading of the foot, according to the American Diabetes Association 1
- High pressure areas develop on the foot, to which the body responds with thickened skin (callus), as noted by the American Diabetes Association 2
- Callus formation further increases abnormal loading, often leading to subcutaneous hemorrhage and eventually ulceration, as reported by the American Diabetes Association 1
Peripheral Arterial Disease (PAD)
- PAD is present in up to 50% of patients with diabetic foot ulcers due to accelerated atherosclerosis, according to the American Heart Association 1, 2
- PAD acts as an important risk factor for impaired wound healing and lower extremity amputation, as noted by the American Heart Association 4
- The combination of infection with PAD is associated with markedly increased risk of poor healing and amputation, as reported by the American Heart Association 6
Infection Pathophysiology
- Infections begin with a break in the protective cutaneous envelope, typically at a site of trauma or ulceration, according to the Infectious Diseases Society of America 4
- Open wounds become colonized with skin flora and, in many cases, ultimately infected, as noted by the Infectious Diseases Society of America 5
- Microorganisms can spread contiguously to subcutaneous tissues, including fascia, tendons, muscles, joints, and bones, as reported by the Infectious Diseases Society of America 6
Contributing Factors
- Poor glycemic control predisposes to infection and impairs wound healing, according to the American Diabetes Association 7
- Diabetes-related immunological perturbations, particularly neutrophil dysfunction, contribute to poor wound healing, as noted by the American Diabetes Association 6
- Chronic renal failure increases risk of foot infection, as reported by the National Kidney Foundation 7
- Foot deformities create areas of high pressure vulnerable to ulceration, according to the American Podiatric Medical Association 8