Microvascular dysfunction in diabetic foot disease and ulceration

Abstract

Diabetic foot disease and ulceration is a major complication that may lead to the amputation of the lower limbs. Microangiopathy may play a significant role in the pathogenesis of tissue breakdown in the diabetic foot. However, the precise mechanisms of this process remain unclear and poorly understood. Microvasculature in the skin is comprised of nutritive capillaries and thermoregulatory arteriovenous shunt flow. It is regulated through the complex interaction of neurogenic and neurovascular control. The interplay among endothelial dysfunction, impaired nerve axon reflex activities, and microvascular regulation in the diabetic patient results in the poor healing of wounds. Skin microvasculature undergoes both morphologic changes as well as functional deficits when parts of the body come under stress or injury. Two important theories that have been put forward to explain the abnormalities that have been observed are the haemodynamic hypothesis and capillary steal syndrome. With advances in medical technology, microvasculature can now be measured quantitatively. This article reviews the development of microvascular dysfunction in the diabetic foot and discusses how it may relate to the pathogenesis of diabetic foot problems and ulceration. Common methods for measuring skin microcirculation are also discussed.

Diabetic foot ulceration and amputation

“…It is the sequelae of these neural dysfunctions in conjunction with extrinsic factors that produce the physiologic and structural changes that lead to ulceration. The most common causal pathway to diabetic foot ulceration involves the confluence of loss of sensation resulting in failure to detect repetitive pressure or trauma and abnormal foot structure or deformity producing sites of abnormally high pressure, usually over areas of bony prominence (Mueller et al, 1990;Brem et al, 2006;Chao and Cheing, 2009;O'Loughlin et al, 2010). Diabetic peripheral polyneuropathy is the central component as it can induce changes in foot structure and produce dryness of the skin which can lead to callus formation (van Schie, 2006;O'Loughlin et al, 2010).…”

“…This classification is a reflection of the physiological systems adversely impacted by the chronic hyperglycemia of the disease. Hyperglycemia induces alterations in multiple metabolic pathways resulting in structural and functional changes in the microvasculature of local tissue and the peripheral nerves in cases of peripheral neuropathy (Chao and Cheing, 2009). Neuropathic ulcers appear in the absence of protective sensation as a result of peripheral sensory neuropathy but without evidence of macrovascular disease.…”

Prospective study on microangiopathy in type 2 diabetic foot ulcer

“…Microangiopathy comprises detrimental changes in both the structure and function of the microcirculation [5]. In diabetic patients, histological abnormalities have been observed in arterioles and capillaries of the foot [6].…”

Assessment of Microcirculation and the Prediction of Healing in Diabetic Foot Ulcers

“…Microcirculation includes the capillaries, arterioles, and venules. These microvessels are arranged in two horizontal network patterns with a superficial subpapillary plexus and a deeper cutaneous plexus with capillary blood flow providing nutrition and arteriovenous shunts that serve a thermoregulatory function (Chao & Cheing, 2009). The nutritional capillaries are organized into functional units within the papillary layer of the dermis.…”

“…Blood flow to the skin runs through this arteriovenous system supplying nutrition, oxygen, and regulating temperature through an increase or decrease of blood flow to the dermal papilla. Blood flow to the skin is controlled by the peripheral sympathetic nervous system via vasodilatory cholinergic and vasoconstrictor adrenergic nerve fibers (Chao & Cheing, 2009) as well as vasoactive substances such as nitric oxide. Additionally, the endothelial basement membrane regulates blood flow and the local inflammatory response via vasoactive substances (Guerci, et al 2001).…”