In diabetes, several specific pathologies contribute to the ulceration of the foot. Functional abnormalities of the microvasculature restrict the delivery of oxygen and other nutrients to the distal tissues of the extremities. The microvascular abnormalities include thickening of the capillary basement membrane,2 arteriovenous shunting,3 and a reduced vasodilatory capacity.4 These combined effects result in impaired soft tissue perfusion. Impaired perfusion has been associated with sensory, motor, and autonomic neuropathy.
In diabetes, several specific pathologies contribute to the ulceration of the foot. Functional abnormalities of the microvasculature restrict the delivery of oxygen and other nutrients to the distal tissues of the extremities. The microvascular abnormalities include thickening of the capillary basement membrane,2 arteriovenous shunting,3 and a reduced vasodilatory capacity.4 These combined effects result in impaired soft tissue perfusion. Impaired perfusion has been associated with sensory, motor, and autonomic neuropathy. The reduction in protective sensation caused by sensory neuropathy allows injury to occur without pain, leading to repetitive trauma that goes unnoticed by the patient, resulting in ulceration. The aforementioned microvascular abnormalities prevent adequate oxygen delivery to the injured area, preventing wounds from healing.The reduced perfusion in the muscle tissue can lead to atrophy and their replacement with fat and connective tissues. Foot muscle atrophy has been related to diabetic peripheral neuropathy in diabetic patients.5 Atrophy of the flexors and extensors is typically unequal and results in clawing of the toes, promoting the prominence of the metatarsal heads, which increases the pressures on the plantar aspect of the foot. This increases the patient’s vulnerability to the development of ulcers. In addition, atrophy and weakening of the plantar muscles reduces their effectiveness in protecting the foot against high mechanical pressures.
It is now understood that the complications that occur in the diabetic foot are not the result of occlusive disease of the small vessels but rather with peripheral diabetic neuropathy. Both conventional X-ray angiography and magnetic resonance angiography (MRA) are capable of identifying occlusive lesions but do not provide an assessment of the functionality of the vessels or their ability to deliver nutrients to local tissue beds. While the total blood flow in the lower limbs of diabetic patients can be adequate for maintaining healthy tissue, it is possible for the perfusion of the local tissues to be impaired.
In the muscle, the energy required for contraction and cellular maintenance functions is supplied by the hydrolysis of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) and inorganic phosphate (Pi).The ATP moiety exists in very low concentrations (approximately four millimollar) in the myocytes and needs to be constantly replenished to maintain the health of the cell. This is accomplished by the creatine kinase reaction when phosphocreatine (PCr) donates its phosphorus atom to convert ADP to ATP. Phosphcreatine is the energy reservoir that maintains the ATP concentration at the level required to maintain cellular function.The reservoir of PCr is maintained by oxidative phosphorylation in the mitocondria, where creatine is converted back to PCr.This process is fueled by oxygen and glucose from the blood.When the tissue beds become ischemic, the supply of oxygen and other nutrients is inadequate for maintaining normal levels of PCr. In ischemic muscle tissue, the concentration of PCr is diminished while that of Pi increases. Under these conditions the concentration of ATP is easily depleted, resulting in the early onset of muscle fatigue and a compromised ability of the cells to carry out normal maintenance functions. If the ischemia persists or increases, the muscle cells eventually die and are replaced by fat and connective tissue. Functional abnormalities of the microvasculature are systemic, therefore the metabolic state of the foot muscles may be a surrogate for other tissues.
