What is foot ulcer?

A foot ulcer is an open sore or wound that develops on the skin of the foot, typically on the bottom (plantar surface) or around the toes. Foot ulcers are a common complication of various medical conditions, particularly diabetes mellitus, peripheral artery disease (PAD), and neuropathy. They can also occur as a result of trauma, pressure, or other factors that impair the blood supply or sensation to the feet.


There are several types of foot ulcers, including:


  • Diabetic Foot Ulcers: Diabetic foot ulcers are one of the most common complications of diabetes mellitus, especially in individuals with poorly controlled blood sugar levels. Diabetes can lead to neuropathy (nerve damage) and peripheral artery disease (PAD), which impair sensation and blood flow to the feet, respectively. Neuropathy can cause loss of sensation, making individuals less aware of injuries or pressure points on their feet, while PAD reduces blood flow, impairing wound healing. As a result, minor injuries or pressure points can develop into ulcers, which may become chronic and difficult to heal.


  • Neuropathic Ulcers: Neuropathic ulcers are caused by peripheral neuropathy, which leads to loss of sensation and altered biomechanics in the feet. Neuropathy can result from diabetes, alcoholism, vitamin deficiencies, infections, or other medical conditions. Neuropathic ulcers often develop at pressure points on the foot due to repetitive trauma, friction, or pressure from ill-fitting footwear. These ulcers are typically painless or associated with minimal discomfort.


  • Ischemic Ulcers: Ischemic ulcers occur as a result of reduced blood flow to the feet, typically due to peripheral artery disease (PAD) or atherosclerosis. Reduced blood flow impairs oxygen and nutrient delivery to the tissues, leading to tissue ischemia and ulcer formation. Ischemic ulcers often develop on the toes, heels, or other areas with poor blood supply and are associated with pain, coolness, and pallor of the affected foot.


  • Pressure Ulcers: Pressure ulcers, also known as bedsores or decubitus ulcers, can develop on the feet of individuals who are immobilized or bedridden for extended periods. Prolonged pressure and friction on bony prominences of the feet can cause tissue damage and ulceration. Pressure ulcers are commonly seen in hospitalized patients, nursing home residents, or individuals with limited mobility due to paralysis, injury, or illness.


What is the relationship between foot ulcer and oxidative stress?

The relationship between foot ulcers and oxidative stress involves complex interactions between various pathophysiological mechanisms, including impaired wound healing, inflammation, and tissue damage. Oxidative stress refers to an imbalance between the production of reactive oxygen species (ROS) and the body’s antioxidant defenses, leading to cellular damage and dysfunction. Several factors related to foot ulcers can contribute to oxidative stress:


  • Ischemia-Reperfusion Injury: In individuals with peripheral artery disease (PAD) or compromised blood flow to the feet, ischemia (reduced blood supply) and subsequent reperfusion (restoration of blood flow) can lead to ischemia-reperfusion injury. Ischemia-reperfusion injury results in the production of ROS, which occurs when tissues are deprived of oxygen during ischemia and then exposed to increased oxygen levels during reperfusion. ROS generated during ischemia-reperfusion can cause oxidative damage to tissues, exacerbating inflammation and impairing wound healing in foot ulcers.


  • Inflammation: Foot ulcers are often associated with inflammation, characterized by the recruitment of immune cells, release of pro-inflammatory cytokines, and activation of inflammatory pathways. Inflammatory cells such as neutrophils and macrophages produce ROS as part of their antimicrobial defense mechanisms to eliminate pathogens and promote tissue repair. However, excessive ROS production can lead to oxidative stress and tissue damage, prolonging inflammation and impairing wound healing in foot ulcers.


  • Impaired Wound Healing: Oxidative stress can impair various stages of the wound healing process, including inflammation, proliferation, and remodeling. Excessive ROS production can disrupt cellular signaling pathways, inhibit cell migration and proliferation, and degrade extracellular matrix components essential for wound repair. In individuals with foot ulcers, oxidative stress may contribute to impaired wound healing, delayed closure of ulcers, and increased risk of infection and complications.


  • Underlying Conditions: Conditions associated with foot ulcers, such as diabetes mellitus and peripheral neuropathy, can exacerbate oxidative stress through various mechanisms. Diabetes is characterized by chronic hyperglycemia (elevated blood sugar levels), which can promote oxidative stress by increasing the production of advanced glycation end-products (AGEs), activating inflammatory pathways, and impairing antioxidant defenses. Peripheral neuropathy, often associated with diabetes, can lead to loss of sensation and altered biomechanics in the feet, increasing the risk of trauma, pressure, and subsequent ulcer formation.


Overall, oxidative stress plays a significant role in the pathogenesis and progression of foot ulcers by exacerbating inflammation, impairing wound healing, and promoting tissue damage.