Watermark. Interaction between Neuropathy and PAD
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1 Interaction between Neuropathy and PAD Javier La Fontaine, DPM, MS Associate Professor Department of Plastic Surgery UT Southwestern Medical Center Dallas, Texas
2 Objectives Understand vascular disease process in patients with diabetes mellitus Macrovascular vs. microvascular dz. The role of Nitric Oxide (NO)
3 Patient Selection????
4 The Problem Wound Failure to heal Infection Hypoxia Macrovascular disease Functional microcirculatory disease Nitric Oxide (NO) Metabolic Abnormalities Glycemic control Nutrition Growth factors
5 DM Patterns of Ischemia Distal: popliteal, trifurcation, tibial, pedal Collateral pathways: internal iliac, profunda femoral, tibial Calcified vessel walls Symmetrical Non DM Proximal: aorta, iliac, femoral Axial Pathways: aorta, iliac, superficial femoral Walls usually noncalcified Symmetrical
6 Macrovascular Disease Multisegmental Distal Involvement Structural Blockage
7 Perfusion Pathophysiology
8 Macrovascular Contributors to Impaired Oxygenation in the Dyslipidemia Hypercholesterolemia Atherosclerosis Atheromatous plaques Diabetic Foot
9 Microvascular Disease
10 Systems affected Retina Skin Kidneys Gum PNS Bone??
11 Anatomy Abnormal blood flow is due to defective C- fiber function DM patients shunt blood away from skin Loss of Autoregulation (Vinik, et.al. Diabetes Care 22: p1549, 1999)
12 Factors that affect endothelial dysfunction (ED) Hypercholesterimia Smoking Diabetes Hypertension Hyperlipidemia
13 The healthy endothelium not only mediates endothelium-dependent vasodilation, but also actively suppresses thrombosis, vascular inflammation, and hypertrophy Landmesser, U. et al. Circulation 2004;109:II-27-II-33 Copyright 2004 American Heart Association
14 Vascular Endothelial Cells G G Basement Membrane G G G Basement Membrane G
15 Vascular Endothelial Cells G G G Basement Membrane G G G Basement Membrane G G G G
16 Vascular Endothelial Cells Basement Membrane ACE tpa Fibronectin Endothelin Basement Membrane
17 Vascular Endothelial Cells Basement Membrane ACE tpa Fibronectin Endothelin Basement Membrane
18 Vascular Endothelial Cells Basement Membrane Nitric Oxide L-Alginine NOS NO Basement Membrane O2 L-Citrulline
19 Nitric Oxide: Vascular Endothelial Mediator Regulation of blood flow Lipoprotein metabolism Capillary transport Angiogenesis Neutralize free radicals N O
20 Microvascular Changes in Increased microvascular pressure and flow (A-V shunting) Endothelial injury Functional Change Increased hydrostatic pressure Type 1 Diabetes Stage 1 Stage 2 Capillary basement membrane thickening Arteriolar hyalinosis Inability to vasodilate Autoregulatory dysfunction Increase permeability (Parving, Metabolism 32, 1983; Tooke, Clin Sci 70, 1986)
21 Early Microvascular Changes in Type 2 Diabetes Reduced insulin sensitivity Nitric Oxide Endotheliumdependent vasodilation Endotheliumindependent vasodilation C-fiber mediated axon (Morris SJ, Tooke JE, Diabetologia 39, 1995)
22 Resultant Structural Modifications Limitation of microvascular dilation Loss of autoregulatory capacity Kidney, Retina, Skin microcirculation affected Worst ESRD Direct correlation with A1c Sandeman et.al. NEJM 327, 1992
23 NO Primary Regulator of the Wound Healing Process Regulation of wound healing NO enhances Wound 02 availability Infection control Mediator of wound repair
24 NO is Significantly Decreased in the Diabetic pt 02 availability Infection control wound repair
25 Non invasive measurements Flow-mediated brachial artery dilatation Endothelial dysfunction=surrogate marker for cardiac risk Apply to all vascular beds Could flow-mediated brachial dilatation used to predict wound healing?? Gokce et.al.: Circulation 105, 2002
26 Future Treatments Thiazolidinediones Troglitazone*, Actos, Avandia, Avandamet Statins- promote repair of endothelium ACE inhibitors Ca++ Channel blockers Fibrates *Caballero et.al.: Metabolism 52, 2003
27 How does it apply to the foot? Transient pressure - induced vasodilation ED does not resolve completely after revascularization Autonomic neuropathy and reduction of neurogenic vascular response Koitka et.al.: Diabetes 53, 2004 Arora et.al.: J Vasc Surg 35, 2002
28 Concept of Ischemia Absolute Ischemia Absolute amount of blood flow present Relative Ischemia Amount of blood needed by current situation Foot that is non-ischemic can be considered ischemic due to increased metabolic need for healing insult
29 Microvascular Disease No Occlusion, but Functional Deficiency Malfunction of Endothelial Cells
30 Macrovascular Microvascular Skin Perfusion
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