1. Pathophysiology of the Foot in Diabetes An 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 ,000 miles
3-4 times around the world!

4. The Structure of the Foot
Lateral Longitudinal Arch
Fifth Metatarsal
Calcaneus
First Metatarsal
Medial Longitudinal Arch
Transverse 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)
1. Peripheral neuropathy
Loss of sensation leading to painless trauma from
Unsuspected foreign body in shoe
Treading on sharp objects (barefoot gait, deep pile carpet!)
Ill-fitting shoes
Repetitive stress of walking
Loss of motor function
Interosseous atrophy leading to cocked-up toes
Loss of proprioception and stretch reflexes
Abnormal joint and position sense
Abnormal small joint adaptation during walking

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

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

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