Diabetic foot pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anahita Deylamsalehi, M.D.[2]Vishnu Vardhan Serla M.B.B.S. [3]

Overview

Diabetic foot is an umbrella term for foot problems in patients with diabetes mellitus. Neuropathy, ischemia and trauma are three main pathogenesis of diabetic foot. Neuropathy is the most common and is the responsible element in more than 60% of diabetic foot cases. Factors such as high blood glucose, reactive oxygen species, insufficient oxygenation of the nerves, and inflammation leads to neuropathy development in diabetic patients and it gets worse with alcohol use and smoking. Neuropathy can involve motor, autonomic, or sensory nerves and is able to involve both large and small fibers. Motor nerve involvement can lead to some mechanical changes in the foot of a diabetic patient, which causes more plantar pressure and higher risk of callus formation. Each and every factor leads to a higher rate of skin breakdown and ulceration. Autonomic neuropathy leads to anhidrosis and impaired function of oil glands, subsequent skin dryness, higher chance of skin breakdown, and ulcer formation. Diabetic patients with sensory neuropathy are more prone to ulcer formation and related complications, since they don't feel pain with ever-deepening ulcers. Ischemia is the second best known pathogenesis of diabetic foot that could occur due to a higher rate of lower limb atherosclerosis in diabetic patients, compared to the normal population. Diabetes related complications such as micro and macrovascular complications further intensify ischemia. Ischemic changes can be discovered by an impaired ankle brachial index (ABI). Trauma to the foot usually acts as a trigger for diabetic foot. A defective hypoxic response has been explained in diabetic foot, which is related to a transcription factor named hypoxia‐inducible factor‐1 (HIF‐1). Lower levels of HIF‐1 in biopsies of diabetic foot could be related to its role in wound healing. Some genetic associations (such as MAPK14 gene located on chromosome 6, decreased expression of certain cytokines and growth factors, and the HSPA1B genotype) have been explained in diabetic foot development. Charcot arthropathy, some psychosocial conditions, necrotizing fasciitis (NF), vitamin D deficiency, tinea pedis, onychomycosis, and diabetic retinopathy are associated conditions in diabetic foot. On gross pathology, the most common site of ulceration is on the soles of the feet, under the metatarsal head with various depths and possible anatomical deformities of the foot. In microscopic evaluations of the ulcers, evidence of necrosis, hyperkeratosis, fibrosis, inflammation, cellular debris, granulation tissue, and angiogenesis have been found.

Pathophysiology

Neuropathy

Ischemia

Neuropathy and angiopathy in the foot have a positive feedback on each other

Trauma

Defective hypoxic response

Genetics

Associated Conditions

Conditions associated with diabetic foot include:[27][28][29][30][31][32]

Gross Pathology

Diabetic foot ulcer, source:wikimedia commons[33]
Charcot joint, source:wikimedia commons



Microscopic Pathology

The following list is a summary of the possible microscopic histopathological changes of diabetic foot:[34][35][36]

References

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