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Orthopaedics
Pathophysiology of Diabetes and Charcot Neuroarthropathy
Built from The Surgical Management of the Diabetic Foot and Ankle
What’s inside
9 sections · 104 slides
Overview
- Scope of this topic
- Structure of the topic
Diabetes Mellitus
- Diabetes mellitus as a disorder of glucose metabolism
- Scale of the disease burden
- Type I and type II diabetes
- Common endpoint of both diabetes types
- Chain from hyperglycemia to limb loss
Charcot Arthropathy
- Definition of Charcot arthropathy
- Changing epidemiology of Charcot arthropathy
- Historical description of the disease
- Swollen foot in the active stage of Charcot arthropathy
- Trigger of the disease process
- Eichenholtz staging of Charcot arthropathy
- Eichenholtz stage I: acute or developmental phase
- Distinguishing Charcot arthropathy from infection
- Eichenholtz stage II: coalescent or quiescent phase
- Eichenholtz stage III: reconstruction phase
- Radiographic appearance of the three Eichenholtz stages
- Disorganised midfoot architecture on a foot radiograph
- Late complications of Charcot arthropathy
- Plantar forefoot ulcer in a diabetic foot
Pathophysiology of Diabetes
- Musculoskeletal consequences of diabetes
- Three systems damaged by diabetes
- Reading the systems table
- Systems impaired by diabetes and their underlying mechanisms
- Abbreviations used in the systems table
The Vascular System
- Vascular disease in diabetes
- Consequences of reduced tissue blood flow
- Normal role of the endothelium
- Mechanism of endothelial cell dysfunction
- Action of peroxynitrite on nitric oxide synthesis
- Vascular smooth muscle dysfunction
- Consequences of proinflammatory gene activation in vessels
- Normal action of insulin on coagulation
- Prothrombotic state in type II diabetes
- Free fatty acids and the NF-kB pathway
- Best current theory of coagulation dysfunction
The Nervous System
- Diabetic neuropathy
- Clinical consequences of diabetic neuropathy
- Mechanisms of peripheral nerve damage
- Interaction between nerve-damaging mechanisms
- Oxidative stress in the nervous system
- Formation of advanced glycation end products
- Effect of advanced glycation end products on soft tissue
- The AGE–RAGE–NF-kB feedback loop
- Consequences of sustained RAGE activation
- Microvascular neurologic disease
- Loss of neural blood flow regulation
- Structural changes in the intraneural vasculature
The Immune System
- Immune dysfunction in diabetes
- Components of the innate immune system
- Complement system changes in diabetes
- Chronically elevated proinflammatory cytokines
- Impaired polymorphonuclear cell chemotaxis
- Blunted monocyte response to bacterial stimulation
- Osteoclast formation driven by RANKL and RANK
- Function of the adaptive immune system
- Two arms of the adaptive immune response
- Macrophage dysfunction and vaccine response
- Glycosylation of immunoglobulin G
- Experimental evidence for glycosylated IgG inactivation
Pathophysiology of Charcot Arthropathy
- The French Theory
- The neurotraumatic theory
- The neurovascular or neurotrophic theory
- Comparison of the two classic theories
- Modern understanding of the pathogenesis
- Interaction between diabetes mellitus and Charcot neuroarthropathy
- Reading the summary diagram
- Role of pain in a normal injury response
- Inflammation as the cause of bone destruction
- Bone mineral density evidence for inflammation
- Immunohistological evidence for inflammation
- Activation of RANKL
- The RANKL–RANK–RAGE axis and osteoclast maturation
- Osteoclastogenic effect of NF-kB signalling
- Osteoprotegerin as the physiological brake
- Mechanism of osteoprotegerin action
- The RANKL to OPG ratio in Charcot arthropathy
- Neuropeptides and bone health
- Calcitonin gene-related peptide
- Actions of calcitonin gene-related peptide on bone
- Nitrous oxide as a bone-regulating neuropeptide
- Combined effect of neuropeptide loss
Summary
- Combined clinical challenge
- Relative contribution of diabetes and neuropathy
- Where to focus understanding
- Recurring molecular themes across all three systems
- Key points to remember
- References
- References (continued)
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- References (continued)
- The Surgical Management of the Diabetic Foot and Ankle