Pathophysiology of chronic limb ischemia

Abstract

Chronic ischemia of the lower extremities is an everyday problem in vascular surgery clinics. In Germany, approximately 3% of all hospitalizations are due to peripheral artery disease (PAD), with critical limb ischemia (CLI) in particular showing a rapid increase. The consequences of chronic undersupply range from reduced walking distance to loss of limbs. At the beginning there are stress factors, such as hyperlipidemia (LDL), free radicals, arterial hypertension, infections or subclinical inflammation that interfere with endothelial homeostasis and cause endothelial dysfunction with increased permeability. Cells of the immune system are attracted and migrate into the vascular wall, where they lead to the degradation of matrix components and destabilization of the plaque. By changing the phenotype of smooth muscle cells and macrophages towards osteoclast-like cells, bone-like hardening of the vessel wall takes place. Above a vessel wall thickness of approximately 100 µm, hypoxia-induced factor (HIF-1α) is intensified by the lack of oxygen, which leads to an increase in growth factors, such as vascular endothelial growth factor (VEGF). This promotes angiogenesis, but it is not sufficient to compensate for a stenosed artery. Arteriogenesis refers to the growth of existing collateral vessels. The driving forces are the pressure gradient before and after the stenosis and the shear forces acting on the vessel walls. In the case of progressive stenosis, the compensatory capacities can be overtaxed and a manifest hypoxia in the tissue with regression of the obtained vascular structures and tissue atrophy occurs.

Severe Type of Minocycline-Induced Hyperpigmentation Mimicking Peripheral Arterial Occlusive Disease in a Bullous Pemphigoid Patient

“…Atherosclerosis leads to a decrease in arterial blood flow, causing distal limb ischemia. This hypoxic state promotes tissue damage and chronic ulcer formation [27]. Venous stasis and recurrent tissue necrosis may lead to pigmentation on bilateral legs.…”

Diagnostic value of ankle peak systolic velocity in diabetic patients with critical limb ischemia

“…Ведущими силами многоступенчатого процесса формирования коллатеральных артерий [14] являются артериальное давление, градиент давления выше и ниже уровня окклюзии и сила напряжения сдвига на стенки моделирующегося сосуда. Исходом артериогенеза является 20-50-кратное увеличение предшествующих артерий [15], которое компенсируют могут частично компенсировать работу магистральных артерий и снижать тяжесть ишемии нижних конечностей.…”

Implications of Hemostasis Disorders in Patients with Critical Limb Ischemia—An In-Depth Comparison of Selected Factors

“…Intermittent claudication (IC) is the most typical symptom; however, IC is estimated to affect about one-third of all patients with PAD [5]. The adaptation of chronically undersupplied tissue manifests in the formation of a collateral network [6]. Limb ischemia is manifested by walking disorders, i.e., pain, fatigue, or muscle contraction, occurring after a certain distance in the buttocks, thighs, calves, or feet, with relief during rest [7].…”

“…Rest pain usually lasts more than two weeks, and is associated with ischemia and common cutaneous lesions and necrosis [5]. In CLI the biological adaptations become overburdened and collateral supply is no longer sufficient to compensate for tissue hypoperfusion [6,9]. Patients with PAD and CLI have some of the highest death risk indicators [3,4,10,11].…”