Pathophysiology of the Foot in Diabetes An Endocrinologist’s Perspective

1. Pathophysiology of the Foot in DiabetesAn Endocrinologist’s Perspective R. Harsha Rao, MD, FRCP Professor of Medicine University of Pittsburgh School of Medicine Chief of Endocrinology, VA Pittsburgh

2. Overview/Objectives • The Foot as a Mechanical Marvel • Structural, and ergonomic complexity • Pedal Bio-mechanics • The Menace posed by Diabetes • Pathophysiology of the “Foot at Risk”

3. The Foot:A Mechanical Marvel • 26 bones, 29 joints, 42 intrinsic muscles • Multitude of tendons and ligaments • Designed to support full weight of the body over a lifetime… • Across 75-100,000 miles • 3-4 times around the world!

4. The Structure of the Foot Lateral Longitudinal Arch Fifth Metatarsal Calcaneus First Metatarsal Transverse Arch Medial Longitudinal Arch

5. Prerequisites for Pedal Integrity Arch Integrity Ligaments/Tendons holding Bones and Joints in place Intrinsic muscles/Long tendons as “shock absorbers” Intact Stretch Reflex Intrinsic muscles and ligaments responsive to stretch Intact nerves for coordinated muscular contraction Preserved Blood Supply Perfusion despite repetitive de-vascularization (pressure) Intact skin To resist repetitive pressure/devascularization To resist infection (and heal quickly)

7. Overview/Objectives • The Foot as a Mechanical Marvel • Structural, and ergonomic complexity • Pedal Bio-mechanics • The Menace posed by Diabetes • Pathophysiology of the “Foot at Risk”

8. Diabetes and the Foot Diabetes is the #1 cause of non-traumatic lower extremity amputations in US 15- to 40-fold more likely in diabetes 60,000-80,000 limbs lost/year (~200/day) Other leg lost within 5 yrs in 50% of patients Foot problems are responsible for 10% of hospitalizations in diabetic patients 25% of all hospital days

9. The Diabetic Foot • Defined as a foot with any pathology that results directly from diabetes mellitus or any of its long-term complications • The presence of several characteristic diabetic foot pathologies is sometimes referred to as the “diabetic foot syndrome”

10. Pathogenesis of the Diabetic Foot • Diabetic neuropathy • Diabetic vasculopathy • Atherosclerotic large vessel disease • Predilection for infections • Impaired immunity • Impaired wound healing

11. Neuropathy in the Diabetic Foot • Peripheral neuropathy • Loss of protective sensation leading to • Painless trauma from • Unsuspected foreign body in shoe • Sharp objects (barefoot gait, pile carpet!) • Ill-fitting shoes • Repetitive stress of walking • Loss of proprioception and stretch reflexes • Abnormal joint and position sense • Abnormal small joint adaptation during walking • Abnormal pressure points, with corns/calluses • Loss of motor function • Interosseous/lumbrical atrophy (cocked-up toes)

13. Diabetic Foot Ulcer

14. Recognizing the “Foot at Risk”

15. The 5.07* (10gm) Monofilament Testing Protective Sensation *Handle Marking (“Size”) = Log10 (Force in mg x 10)

16. Pathogenesis of the Diabetic Foot • Diabetic neuropathy • Diabetic vasculopathy • Atherosclerotic large vessel disease • Predilection for infections • Impaired immunity • Impaired wound healing • Diabetic neuropathy • Diabetic vasculopathy • Atherosclerotic large vessel disease • Predilection for infections • Impaired immunity • Impaired wound healing

17. PAD + Neuropathy PAD only Pathogenesis of Diabetic Wounds 50% 2/3 1/3 50% Neuropathic Ischemic

18. Interplay of Neuropathy and PAD Neuropathy “Auto-sympathectomy” Cutaneous Vascular Diversion Arterial Insufficiency Worsens nerve ischemia Exacerbates neuropathy Diabetic Foot Wounds

19. Pathogenesis of the Diabetic Foot • Diabetic neuropathy • Diabetic vasculopathy • Atherosclerotic large vessel disease • Predilection for infections • Impaired immunity • Impaired wound healing • Diabetic neuropathy • Diabetic vasculopathy • Atherosclerotic large vessel disease • Predilection for infections • Impaired immunity • Impaired wound healing

20. Predilection for infections Hyperglycemia • Impairs Neutrophil function • Adhesion, chemotaxis, phagocytosis, bacterial kill • Impairs cytokine production • Impairs immunoglobulin response • Impairs immunoglubulin action (glycosylation) • Impairs inflammatory cell activation • Increases pathogenic colonization (bacterial, candidal)

21. Lower Extremity Infections in Diabetes • Cellulitis • Deep soft tissue infection • Bone Infection • Osteomyelitis

22. Cellulitis

23. Deep Soft Tissue Infection • Patient is often acutely ill • Wound discharge usually not present • Possible compartment syndrome • May be gas in tissue • Mixed aerobic/anerobic infection (common) • Gas gangrene (rare)

24. Pathogenesis • Diabetic neuropathy • Diabetic vasculopathy • Atherosclerotic large vessel disease • Predilection for infections • Impaired immunity • Impaired wound healing • Diabetic neuropathy • Diabetic vasculopathy • Atherosclerotic large vessel disease • Predilection for infections • Impaired immunity • Impaired wound healing

25. Impaired Wound Healing • Reduced tensile strength of wounds • Defective matrix production/deposition • Advanced glycation and cross-linking of matrix protein • Diminished cutaneous perfusion • Peripheral Arterial Disease • Autonomic neuropathy • Aberrant growth factor expression • Delayed replication and excess cell death in vascular endothelial cells • Increased production of reactive oxygen species (ROS)

26. The Pathology of the Diabetic Foot…   • Arch integrity maintained by ligaments holding bones and joints together • Arch support from coordinated action of intrinsic muscles and long tendons (“shock absorber”) • Intrinsic muscles and ligaments responsive to stretch • Intact nerves to coordinate muscular action and mediate the stretch reflex • Good blood supply to perfuse tissues compressed by repetitive pressure • Intact, healthy skin, able to resist repetitive pressure, heal quickly (and resist infection)    

27. An Ode to the Diabetic Foot Decreased feeling, Delayed healing Fungus carrier, defective skin barrier Sugar high, bugs multiply Poor blood supply, And feet go ‘bye-bye’! Harsha Rao