diab neuropa etiol mech con

1. 1
Diabetic Neuropathy - EtiologyDiabetic Neuropathy - Etiology
Mechanisms and ConsequencesMechanisms and Consequences
Sanjeev KelkarSanjeev Kelkar
Conjoint LecturerConjoint Lecturer
Faculty of HealthFaculty of Health
University of NewcastleUniversity of Newcastle
AustraliaAustralia

2. 2
Risk Factors ForRisk Factors For
Diabetic NeuropathyDiabetic Neuropathy
• MODIFIABLEMODIFIABLE
• HYPERGLYCEMIAHYPERGLYCEMIA
• HYPERTENSIONHYPERTENSION
• INCREASEDINCREASED
CHOLESTEROLCHOLESTEROL
• SMOKINGSMOKING
• ALCOHOL USEALCOHOL USE
• NON MODIFIABLENON MODIFIABLE
• OLD AGEOLD AGE
• LONG DURATIONLONG DURATION
OF DIABETESOF DIABETES
• HLA-DR 3/4HLA-DR 3/4
GENOTYPEGENOTYPE
• GREATER HEIGHTGREATER HEIGHT

3. 3
Etiology Of Diffuse Neuropathy - 1Etiology Of Diffuse Neuropathy - 1
• HyperglycemiaHyperglycemia
• Vasa nervorum closureVasa nervorum closure
• Abnormal fatty acid metabolismAbnormal fatty acid metabolism
• Myo inositol deficiencyMyo inositol deficiency

4. 4
Etiology Of Diffuse Neuropathy - 2Etiology Of Diffuse Neuropathy - 2
• Advanced glycated end productsAdvanced glycated end products
• Antibodies to neural tissuesAntibodies to neural tissues
• Neural growth factorsNeural growth factors

5. 5
Diabetic Neuropathy –Diabetic Neuropathy –
PrevalencePrevalence
Neuropathy that is significant enough toNeuropathy that is significant enough to
cause foot ulceration may affect 40% ofcause foot ulceration may affect 40% of
diabetic population especially elderlydiabetic population especially elderly
with type 2 diabetes.with type 2 diabetes.
Asymptomatic neuropathy 35%Asymptomatic neuropathy 35%

6. 6
Feet ComplicationsFeet Complications
4%
1% 1%
37%
Healed Ulcer
Acute Ulcer / Gangrene
Neuropathy
Leg Amputation

7. 7
Current Co-Morbid ConditionsCurrent Co-Morbid Conditions

8. 8
Severe Late ComplicationsSevere Late Complications
1%
7%
3%
1% 1%
Legal Blindness MI/CABG/Angioplasty
Stroke ESRD Leg Amputation

9. 9
Diabetes ComplicationsDiabetes Complications
In Relation To Diabetes DurationIn Relation To Diabetes Duration
60%
35%
29%
64%
32%
19%12%
5% 4%4% 2% 2%2%
<5y5-10y>10y
Foot Eye MI Stroke ESRD
n=480n=626n=901

10. 10
Components of neuropathic footComponents of neuropathic foot
transforming to diabetic foot - 1transforming to diabetic foot - 1
• A. Components of Ulcerative diabeticA. Components of Ulcerative diabetic
neuropathic footneuropathic foot
• B. Non-ulcerative neuropathic pathologiesB. Non-ulcerative neuropathic pathologies
in diabetic footin diabetic foot

11. 11
A. Components of ulcerativeA. Components of ulcerative
diabetic neuropathic foot - 2diabetic neuropathic foot - 2
1. Neuropathic & Neuroischemic foot1. Neuropathic & Neuroischemic foot
2. Neuropathic foot deformities2. Neuropathic foot deformities
a. Clawed toesa. Clawed toes
b. Pes cavusb. Pes cavus
c. Hallux rigidus and valgusc. Hallux rigidus and valgus
d. Hammer toed. Hammer toe
e. Nail deformitiese. Nail deformities

12. 12
A. Components of ulcerativeA. Components of ulcerative
diabetic neuropathic foot - 3diabetic neuropathic foot - 3
3. Neuropathic callus3. Neuropathic callus
4. Neuropathic ulcers4. Neuropathic ulcers
a. Ulcer over pressure points ona. Ulcer over pressure points on
sole, later callus ulcerssole, later callus ulcers
b. Decubitus ulcersb. Decubitus ulcers
c. Puncture wound ulcersc. Puncture wound ulcers
d. Traumatic ulcersd. Traumatic ulcers

13. 13
Components of Diabetic Foot - 4Components of Diabetic Foot - 4
Three components of neuropathy:Three components of neuropathy:
*sensory – painful, painless*sensory – painful, painless
*Motor*Motor
*Autonomic*Autonomic
All contribute to diabetic foot and orAll contribute to diabetic foot and or
ulcerationulceration

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Components of Diabetic Foot -Components of Diabetic Foot -
55
Rather than acting in isolation neuropathyRather than acting in isolation neuropathy
exerts its vicious effectsexerts its vicious effects
in concert with angiopathy andin concert with angiopathy and
immunopathy leading to ulcerationimmunopathy leading to ulceration
and infectionsand infections

15. 15
B. Non-ulcerative neuropathicB. Non-ulcerative neuropathic
pathologies in diabetic footpathologies in diabetic foot
1. Charcot’s Foot1. Charcot’s Foot
Acute / chronic bone destruction andAcute / chronic bone destruction and
deformed diabetic foot and toes withdeformed diabetic foot and toes with
pathological fracturespathological fractures
2. Diabetic painful neuropathy2. Diabetic painful neuropathy

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17. 17

18. 18
Diabetic foot – Mechanisms - 1Diabetic foot – Mechanisms - 1
Loss of pain sensation resultsLoss of pain sensation results
in neuropathic injury due to,in neuropathic injury due to,
repeated unrecognized trauma,repeated unrecognized trauma,
inflicted in many different waysinflicted in many different ways

19. 19
Diabetic foot – Mechanisms - 2Diabetic foot – Mechanisms - 2
Loss of sensation of joint position causesLoss of sensation of joint position causes
the foot to land in abnormal foot positionthe foot to land in abnormal foot position
on ground leading to areas of excessiveon ground leading to areas of excessive
and low pressure leading to injury duringand low pressure leading to injury during
walking or if the shoes are not properlywalking or if the shoes are not properly
selected will hurt at placesselected will hurt at places

20. 20
Diabetic foot – Mechanisms - 3Diabetic foot – Mechanisms - 3
Motor NeuropathyMotor Neuropathy
* Wasting of small intrinsic muscles of foot* Wasting of small intrinsic muscles of foot
leading to weaknessleading to weakness
*Imbalance between the flexor and*Imbalance between the flexor and
extensor musclesextensor muscles

21. 21
Diabetic foot – Mechanisms - 4Diabetic foot – Mechanisms - 4
Intrinsic deformityIntrinsic deformity
Clawing of the toesClawing of the toes
Prominence of metatarsal headsProminence of metatarsal heads
Flattening of the archFlattening of the arch

22. 22

23. 23
Diabetic foot – Mechanisms - 5Diabetic foot – Mechanisms - 5
Abnormal distribution of body weight,Abnormal distribution of body weight,
concentrated on smaller areas likeconcentrated on smaller areas like
metatarsal head and the heel.metatarsal head and the heel.
Excess pressure loading of these areasExcess pressure loading of these areas
finally results in callus formation.finally results in callus formation.
Rise of Pressure > 30 times at callusRise of Pressure > 30 times at callus

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Diabetic foot – Mechanisms - 6Diabetic foot – Mechanisms - 6
Connective tissue changesConnective tissue changes
Hyperglycemia causes non enzymaticHyperglycemia causes non enzymatic
glycation of collagen and keratinglycation of collagen and keratin
Increase in cross linkingIncrease in cross linking
Become rigid and inflexibleBecome rigid and inflexible
Tissue break down in places where thereTissue break down in places where there
is high horizontal shear forceis high horizontal shear force

25. 25
Diabetic foot – Characteristics of aDiabetic foot – Characteristics of a
Neuropathic ulcerNeuropathic ulcer
* Painless - Develops on pressure points* Painless - Develops on pressure points
(metatarsal heads/heel)(metatarsal heads/heel)
* Pulsations intact unless superadded* Pulsations intact unless superadded
ischaemia is also presentischaemia is also present
* Decrease in* Decrease in pain / temperature as alsopain / temperature as also
in the vibration perceptionin the vibration perception
* Punched out ulcer surrounded by callus* Punched out ulcer surrounded by callus
* Most ulcers from within out* Most ulcers from within out

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Neuropathic (n) / Ischemic ulcer (i)Neuropathic (n) / Ischemic ulcer (i)
Site Pressure points (n)Site Pressure points (n)
Sides / tips of toes (i)Sides / tips of toes (i)
Pain --- ( n ) +++ ( i )Pain --- ( n ) +++ ( i )
Callus ++ ( n ) --- ( i )Callus ++ ( n ) --- ( i )
Pulse ++ ( n ) --- ( i )Pulse ++ ( n ) --- ( i )
ABI > 1( n ) < .6 ( i )ABI > 1( n ) < .6 ( i )
Healing ++ ( n ) --- ( i )Healing ++ ( n ) --- ( i )

27. 27
Autonomic neuropathy - 1Autonomic neuropathy - 1
* Damages the sympathetic innervation of* Damages the sympathetic innervation of
lower limblower limb
* This results in* This results in
Decreased sweatingDecreased sweating
Results in dry skin fissures / cracksResults in dry skin fissures / cracks
Super added infectionSuper added infection

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Autonomic neuropathy - 2Autonomic neuropathy - 2
Opening of arteriovenous channelsOpening of arteriovenous channels
Warm skin ( misleadingly healthy )Warm skin ( misleadingly healthy )
Shunting of nutrients and oxygen fromShunting of nutrients and oxygen from
the tissuesthe tissues
Impaired vascular response to infectionImpaired vascular response to infection

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30. 30

31. 31
Autonomic neuropathyAutonomic neuropathy
classical signsclassical signs
Dry skinDry skin
FissuringFissuring
Distended veins over the dorsum of footDistended veins over the dorsum of foot
and the ankleand the ankle

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Neuropathic joint orNeuropathic joint or
Charcot’s arthropathy - 1Charcot’s arthropathy - 1
1868 French neurologist I.M. Charcot1868 French neurologist I.M. Charcot
First described in tabesFirst described in tabes
Can also be seen in leprosy, syringomyelia,Can also be seen in leprosy, syringomyelia,
hereditary sensory neuropathy,hereditary sensory neuropathy,
Charcot Marie Tooth disease etcCharcot Marie Tooth disease etc

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Neuropathic joint orNeuropathic joint or
Charcot’s arthropathy - 2Charcot’s arthropathy - 2
Relatively rareRelatively rare
Potentially devastating disorderPotentially devastating disorder
Long standing diabetesLong standing diabetes
Dense peripheral neuropathyDense peripheral neuropathy
Peripheral vascular disease is typicallyPeripheral vascular disease is typically
absentabsent

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Neuropathic joint orNeuropathic joint or
Charcot’s arthropathy - 1Charcot’s arthropathy - 1
Sympathetic failure-- increased bloodSympathetic failure-- increased blood
flow due to arteriovenous anastomosisflow due to arteriovenous anastomosis
Bone demineralisation (diabeticBone demineralisation (diabetic
osteopenia)osteopenia)
Susceptibility to minor, recurrent fracturesSusceptibility to minor, recurrent fractures

35. 35
Fig
Charcot’s
Foot with
Acute Stage
of
Destruction

36. 36
Neuropathic joint orNeuropathic joint or
Charcot’s arthropathy - 4Charcot’s arthropathy - 4
Painless disintegration of bone in responsePainless disintegration of bone in response
to trivial traumato trivial trauma
Common joints involved areCommon joints involved are
– Tarso metatarsalTarso metatarsal
– Metatarso phalangealMetatarso phalangeal
– Ankle jointAnkle joint
– Knee jointKnee joint

37. 37Fig Bilateral Charcot’s Foot in Acute Stage of Destruction

38. 38
Neuropathic joint orNeuropathic joint or
Charcot’s arthropathy - 5Charcot’s arthropathy - 5
Acute Charcot’s arthropathy may mimicAcute Charcot’s arthropathy may mimic
infectioninfection
Chronic Charcot’s foot is classicallyChronic Charcot’s foot is classically
described as ‘bag of bones’described as ‘bag of bones’
(Gross destruction of joint surfaces and(Gross destruction of joint surfaces and
bone with effusion which is typicallybone with effusion which is typically
painless)painless)

39. 39
Neuropathic joint orNeuropathic joint or
Charcot’s arthropathy - 6Charcot’s arthropathy - 6
Differentiation from osteomyelitis is difficultDifferentiation from osteomyelitis is difficult
* TC 99 Scan* TC 99 Scan
* Indium labeled white cell scan* Indium labeled white cell scan
* MRI* MRI

40. 40
Neuropathic joint orNeuropathic joint or
Charcot’s arthropathy - 7Charcot’s arthropathy - 7
Early diagnosis and intervention are importantEarly diagnosis and intervention are important
to prevent deformity and loss of functionto prevent deformity and loss of function
Treatment includesTreatment includes
*Long term immobilization in plaster of Paris*Long term immobilization in plaster of Paris
cast, (up to even 1 year)cast, (up to even 1 year)
*Charcot’s Restraint Orthotic Walker (CROW)*Charcot’s Restraint Orthotic Walker (CROW)
which allows pressure to be off loadedwhich allows pressure to be off loaded
*Pamidronate - tried as a new treatment of*Pamidronate - tried as a new treatment of
Charcot’s arthropathyCharcot’s arthropathy

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Diabetic Neuropathy and Ulcers –Diabetic Neuropathy and Ulcers –
Economic ConsequencesEconomic Consequences - 1- 1
Neuropathy that is significant enough toNeuropathy that is significant enough to
cause foot ulceration may affect 40% ofcause foot ulceration may affect 40% of
diabetic population especially elderlydiabetic population especially elderly
with type 2 diabetes.with type 2 diabetes.

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Diabetic Neuropathy and Ulcers –Diabetic Neuropathy and Ulcers –
Economic ConsequencesEconomic Consequences - 2- 2
• DFU - cause for more amputation than anyDFU - cause for more amputation than any
other pathology.other pathology.
• Most contemporary and challenging issueMost contemporary and challenging issue

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Diabetic Neuropathy and Ulcers –Diabetic Neuropathy and Ulcers –
Economic ConsequencesEconomic Consequences - 3- 3
• Foot ulcers result inFoot ulcers result in
MorbidityMorbidity
MortalityMortality
Enormous health care expenditureEnormous health care expenditure
Psychosocial problemsPsychosocial problems

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Diabetic Neuropathy and Ulcers –Diabetic Neuropathy and Ulcers –
Economic ConsequencesEconomic Consequences - 4- 4
• 5-10% of all diabetic patients have foot5-10% of all diabetic patients have foot
ulceration of various degrees and aboutulceration of various degrees and about
1% undergo amputation1% undergo amputation
• Diabetes accounts for up to 50% of nonDiabetes accounts for up to 50% of non
traumatic leg amputationstraumatic leg amputations
• Of all the diabetic amputees about 50%Of all the diabetic amputees about 50%
will lose their life or their other leg by 3will lose their life or their other leg by 3
yearsyears

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Total Mean Duration ofTotal Mean Duration of
HospitalizationHospitalization
Cause SpecificCause Specific
14.7
8.2
14.5
13.9
32.5
9.4
11.1
21.5
25.7
6.7
16.0
13.2
0
10
20
30
40
50
60
Heart
Neuro
Eye
NHW
Kidney
HBP
Skin
TB
Paralysis
Hyper
Hypo
Other
Days

46. 46
Total Mean Hospitalization CostTotal Mean Hospitalization Cost
CauseCause SpecificSpecific
11.2
7.7
19.6
7.6
5.9
11.2
7.1
13.9
27.5
0
20
40
60
80
100
Heart
Neuro
Eye
NHW
HBP
Skin
Hyper
Hypo
Other
MeanCostinINR('000)

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TEN COMMANDMENTS OF DIABETICTEN COMMANDMENTS OF DIABETIC
FOOT CAREFOOT CARE
1.1. DO NOTDO NOT walk barefootwalk barefoot..
2.2. INSPECTINSPECT the feet daily for blisters, wounds,the feet daily for blisters, wounds,
bleeding, smell, increased temperature at pressurebleeding, smell, increased temperature at pressure
points of feet.points of feet.
3.3. DDO NOTO NOT apply hot fomentation / coldapply hot fomentation / cold
compresses / electric heating pads / strong countercompresses / electric heating pads / strong counter
irritant ointments to legs & feet.irritant ointments to legs & feet.
4.4. USEUSE correct footwear. Choose your footwear aftercorrect footwear. Choose your footwear after
consulting your doctor. Always wear footwear withconsulting your doctor. Always wear footwear with
socks with loose elastic.socks with loose elastic.

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TEN COMMANDMENTS OF DIABETICTEN COMMANDMENTS OF DIABETIC
FOOT CAREFOOT CARE
5.5. DO NOTDO NOT walk bearing weight on affectedwalk bearing weight on affected
foot in case of presence of wounds or afterfoot in case of presence of wounds or after
surgery.surgery.
6.6. DO NOTDO NOT sit cross legged for long timesit cross legged for long time..
7.7. DO NOTDO NOT remove foot wear during travelremove foot wear during travel
and place your feet on the floor of theand place your feet on the floor of the
vehicle. This can cause burns.vehicle. This can cause burns.

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TEN COMMANDMENTS OFTEN COMMANDMENTS OF
DIABETIC FOOT CAREDIABETIC FOOT CARE
8.8. CUTCUT the nails regularly, trim them square.the nails regularly, trim them square.
9.9. DO NOTDO NOT cut corns / calluses with blade orcut corns / calluses with blade or
knife. Home surgery is dangerous.knife. Home surgery is dangerous.
10.10. CLEANCLEAN the feet twice a day with soap andthe feet twice a day with soap and
water. Wipe the web spaces dry and applywater. Wipe the web spaces dry and apply
softening agent to feet.softening agent to feet.
OrdainedOrdained ByBy Dr. Arun BalDr. Arun Bal

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Diabetic Neuropathy and Ulcers –Diabetic Neuropathy and Ulcers –
Need of the hourNeed of the hour
• Paucity of data regarding prevalence ofPaucity of data regarding prevalence of
diabetic foot in India, data from only a fewdiabetic foot in India, data from only a few
places – need moreplaces – need more
• St. Vincent’s and Health 21 WHOSt. Vincent’s and Health 21 WHO
Declaration have called for reduction inDeclaration have called for reduction in
amputation in diabetic foot.amputation in diabetic foot.
• Efforts required to create awareness andEfforts required to create awareness and
commitmentcommitment

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Effect Of Patient Education OnEffect Of Patient Education On
Amputation RatesAmputation Rates
Knee & Above
12%
15%
5%
46%
35%
60%
Toe & Metatarsal
Below Knee
No Education
Education
University Hospital of Geneva 1979-1989. All comparisons p<0.001. Assal JP et
al. Diabete Metab 1993.

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Factors and markers of low-risk versus high-Factors and markers of low-risk versus high-
risk diabetic feetrisk diabetic feet
Low-risk foot High-risk footLow-risk foot High-risk foot
All of the following:All of the following: One or more of theOne or more of the
following:following: following:following:
Intact protective sensation Loss of protectiveIntact protective sensation Loss of protective
sensationsensation
Pedal pulses present Absent pedal pulsesPedal pulses present Absent pedal pulses
No severe deformity Significant footNo severe deformity Significant foot
deformitydeformity

53. 53
Factors and markers of low-risk versus high-Factors and markers of low-risk versus high-
risk diabetic feetrisk diabetic feet
Low-risk foot High-risk footLow-risk foot High-risk foot
All of the following:All of the following: One or more of theOne or more of the
following:following: following:following:
No prior foot ulcer History of foot ulcer orNo prior foot ulcer History of foot ulcer or
callus pre-ulcerative calluscallus pre-ulcerative callus
No amputation Prior amputationNo amputation Prior amputation
Normal joint mobility. Limited joint mobilityNormal joint mobility. Limited joint mobility

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Diabetic Foot Wounds Are LikeDiabetic Foot Wounds Are Like
ICEBERGICEBERG

55. 55
Diabetic neuropathyDiabetic neuropathy
Scope of the syndrome - 2Scope of the syndrome - 2
• DiffuseDiffuse
• 1. Distal symmetric sensorimotor1. Distal symmetric sensorimotor
• polyneuropathypolyneuropathy
• 2. Autonomic neuropathy2. Autonomic neuropathy
• A.SudomotorA.Sudomotor
• B.CardiovascularB.Cardiovascular
• C.GastrointestinalC.Gastrointestinal
• D.GenitourinaryD.Genitourinary