Pathophysiology Behind Diabetic Foot Ulcers
Diabetic foot ulcers result from multiple interacting pathological mechanisms, with diabetic peripheral neuropathy playing the central role alongside peripheral arterial disease, foot deformities, and abnormal biomechanical loading of the foot.1
Primary Pathophysiological Mechanisms
Diabetic Peripheral Neuropathy
- Neuropathy leads to an insensitive and sometimes deformed foot, causing abnormal walking patterns 1
- Loss of protective sensation allows minor trauma (from ill-fitting shoes, walking barefoot, or acute injury) to go unnoticed, precipitating ulceration 1
- Motor neuropathy contributes to foot deformities such as claw toes and hammer toes, creating areas of high pressure 1
- Autonomic neuropathy reduces sweating, leading to dry skin prone to cracking 1
Biomechanical Abnormalities
- Loss of sensation, foot deformities, and limited joint mobility result in abnormal biomechanical loading of the foot 1
- High pressure areas develop on the foot, to which the body responds with thickened skin (callus) 1
- Callus formation further increases abnormal loading, often leading to subcutaneous hemorrhage and eventually ulceration 1
- Continued walking on the insensitive foot impairs wound healing, creating a vicious cycle 1
Peripheral Arterial Disease (PAD)
- Present in up to 50% of patients with diabetic foot ulcers due to accelerated atherosclerosis 1
- Acts as an important risk factor for impaired wound healing and lower extremity amputation 1
- While rarely the primary cause of foot wounds, PAD increases the risk of wound infection and adversely affects outcomes 1
- The combination of infection with PAD is associated with markedly increased risk of poor healing and amputation 1
Types of Diabetic Foot Ulcers
- Neuropathic ulcers: Primarily caused by unperceived repetitive trauma on a foot with loss of protective sensation 1
- Ischemic ulcers: Usually painful, caused by minor trauma in the setting of significant PAD 1
- Neuro-ischemic ulcers: The majority of diabetic foot ulcers, caused by combined neuropathy and ischemia; symptoms may be absent despite severe pedal ischemia due to neuropathy 1
Infection Pathophysiology
- Infections begin with a break in the protective cutaneous envelope, typically at a site of trauma or ulceration 1
- Open wounds become colonized with skin flora and, in many cases, ultimately infected 1
- Microorganisms can spread contiguously to subcutaneous tissues, including fascia, tendons, muscles, joints, and bones 1
- The compartmentalized anatomy of the foot fosters proximal spread of infection 1
- Inflammatory response to infection may cause compartmental pressure to exceed capillary pressure, leading to ischemic tissue necrosis 1
- Tendons within compartments facilitate proximal spread of infection from higher to lower pressure areas 1
Contributing Factors
- Poor glycemic control predisposes to infection and impairs wound healing 1
- Diabetes-related immunological perturbations, particularly neutrophil dysfunction 1
- Chronic renal failure increases risk of foot infection 1
- Hyperglycemia-induced advanced glycation end products contribute to chronic wounds 1
- Persistent inflammation and apoptosis delay healing 1
- Foot deformities create areas of high pressure vulnerable to ulceration 1
Progression and Complications
- If not diagnosed and properly treated, diabetic foot infections tend to progress, sometimes rapidly 1
- The combination of infection with PAD significantly increases the risk of amputation 1
- Systemic symptoms (fever, marked leukocytosis, metabolic disturbances) are uncommon but denote severe, potentially limb-threatening infection 1
- Diabetic microangiopathy (small vessel disease) is not likely to be the primary cause of ulcers or poor wound healing 1
Understanding this complex pathophysiology is essential for implementing effective prevention strategies and treatment approaches to reduce the significant morbidity and mortality associated with diabetic foot ulcers.