Diabetic Foot Pathophysiology Professor Donald G. MacLellan Executive Director Health Education & Management Innovations
AGEs & RAGEs in Diabetes AGE levels increased & RAGEs highly expressed in diabetic complications AGEs activate RAGE expression AGEs & RAGEs responsible for inflammatory & oxidative stress responses Circulating soluble RAGE (srage) and endogenous secretory RAGE (esrage) can counteract damaging effects of RAGE
AGEs & RAGEs in Diabetes Inhibiting AGEs can reduce complications such as Peripheral Neuropathy srage & esrage have protective effects Some nutrients have an affect on AGE/RAGE Worsening fructose corn syrup, refined carbs, high temp cooking Helping boiling, low temp cooking, marinating meats (red wine & herbs) Also supplements with Carnosine, Guava, Yerba mate, Lipoic acid
Diabetic Foot Ulceration Diabetic pathophysiology affects - Nerves Microvasculature Small foot muscles
Diabetic Foot Ulceration Nerves: Vasa Nervorum diseased Peripheral sensation diminished Vasomotor neuropathy Diminished sweating dry skin, dystrophic nails
Diabetic Foot Ulceration Microvasculature: Abnormal endothelial function Thickened BM & capillary wall fragility Vasomotor Neuropathy - loss of fine vasomotor control of the pedal circulation Arterio-venous shunting Reduced art. distribution to areas of need Resultant tissue ischaemia (despite palpable pedal pulses and distended veins)
Diabetic Foot Ulceration Small foot muscles: Altered innervation of the small muscles of the foot Altered distribution of forces during walking Thickened Plantar Aponeurosis & Claw foot
Foot deformities. Andrew J.M. Boulton et al. Dia Care 2008;31:1679-1685 2008 by American Diabetes Association
Tendon Pathology DIABETES OBESITY Hypercholesterolaemia Hypercholesterolaemia Hyperuricaemia AGEs & RAGEs Cholesterol Deposits Uric Acid Deposition Adipokines Low Grade Inflammation TENDON DAMAGE
Diabetes and Infection
Risk Factors for Ulceration Previous amputation Past foot ulcer history Peripheral neuropathy Foot deformity Peripheral vascular disease Visual impairment Diabetic nephropathy (esp. patients on dialysis) Poor glycemic control Cigarette smoking
Diabetic Foot Examination Inspection skin status: colour, thickness, dryness, cracking sweating infection: check between toes for fungal infection ulceration calluses/blistering: haemorrhage into callus?
Diabetic Foot Examination Musculoskeletal: deformity, e.g., claw toes, prominent metatarsal heads, Charcot joint muscle wasting (guttering between metatarsals)
Diabetic Foot Examination Neurological assessment: 10-g monofilament + 1 of the following 4 vibration using 128-Hz tuning fork pinprick sensation ankle reflexes vibration perception threshold
Upper panel: For performance of the 10-g monofilament test, the device is placed perpendicular to the skin, with pressure applied until the monofilament buckles. Andrew J.M. Boulton et al. Dia Care 2008;31:1679-1685 2008 by American Diabetes Association
Diabetic Foot Examination Vascular assessment: General art exam foot pulses ABI, if indicated perfusion assessment, if indicated eg. Toe Pressure, Transcut Oxygen Tension
Arterial Insufficiency Ulcers Treat the Cause Vascular assessment is e.g. sequential Doppler Revascularization is the key to treatment where possible Angioplasty Stents Bypass (Vascular grafts, synthetic) Medical Management ABCs Hgb A1C, BP, Cholesterol Graduated exercise program Stop Smoking Every cigarette will decrease the circulation in the leg or foot up to 30% for an hour. Smoking interferes with healing Stimulates atherosclerosis Second hand smoking is harmful Drugs? Dalteparin (Fragmin) Anti-platelet drugs Pentoxifylline?
Osteomyelitis: Infection Infection: If an ulcer probes to bone, there is a high incidence of Osteomyelitis Grayson et al, 1994 Lavery et al. 2007 Sensitivity: 66% 87% Specificity: 85% 91% + pred. value 89% 57-62% X-rays may be less reliable
Diabetic Foot Ulceration Principles of management: Treat any infection Check if ischaemia can be revascularised Keep forces on ulcered area to a minimum Improve wound /ulcer bed by debridement, callus removal & topical applications Prevent ulcer recurrence