Highest Marks-18/20

• Cuckoo Sarah Kuruvilla

• Jacob Cyriac
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• Naveen K. Jose
• Rejith K.R.
Dr John S Kurien MS,DipNB,FAIS
Associate Prof of Surgery,
Medical College, Kottayam,
Kerala
 Magnitude of Problem
• In developing countries the diabetic foot represents a
major cause of morbidity, mortality and enormous
treatment cost. (According to estimates, in year 2000,
there were 31.7 million cases of Diabetes in India and
the figure is expected to rise further to 79.4 million
cases by year 2030 )
“Early detection and appropriate treatment of diabetic
foot ulcer can prevent large number of complications
including amputations”
• EVERY HOSPITALIZATION COSTS RS. 25
TO 30 THOUSAND
• 50% NON TRAUMATIC AMPUTATIONS
ARE DUE TO DIABETES
• 85% OF THESE AMPUTATIONS ARE DUE
TO UNTREATED AND/OR
INADEQUATELY TREATED DIABETIC
FOOT ULCERS
• 60% INDOOR ADMISSIONS ARE DUE
TO THE FOOT INFECTIONS
• MAJORITY OF DIABETIC FOOT
ULCERS IN INDIA ARE
NEUROPATHIC INFECTIVE
• 15% LESIONS HAVE ASSOCIATED
VASCULOPATHY
 Diabetic foot ulcers
• These usually involve clinical triad of
Diabetic Foot Ulcers
 Diabetic Foot Ulcers

Diabetic foot ulcers with amputation in other foot

 REALITIES
40,000 lower extremity
amputation per year

Commonest indication is infected

neuropathic foot
potentially preventable
 WHY DIABETIC FOOT LESIONS
ARE MANY A TIMES MISSED?
• USUAL SIGNS AND SYMPTOMS OF
INFECTION ARE ABSENT
• PATIENT DOES NOT COMPLAIN OF
PAIN
• LOW LEVEL OF AWARENESS AT
PRIMARY HEALTHCARE LEVEL
• DIABETIC FOOT LESIONS ARE
SILENT
Risk factor for diabetic foot ulcers
• Diabetes of longer duration
• Poor glycemic control
• Peripheral neuropathy
 Somatic –Sensory & motor
 Autonomic
• Abnormal structure of foot (bony abnormalities,
callus, thickened nails)
• History of previous ulcer or amputation.
• Peripheral vascular disease
 DIABETES MELLITUS

NEUROPATHY PERIPHERAL MICRO-ANGIOPATHY

VASCULAR DISEASE

SOMATIC AUTONOMIC

Reduced Pain & Restricted Absence of Impaired

proprioception joint mobility Sweating blood flow
regulation

Increased Dry skin FOOT

Foot fissures ISCHEMI
Pressures A

Small muscle CALLUS

weakness
INFECTION
FOOT ULCERATION
 HIGH FOOT PRESSURES
It is the combination with neuropathy and high foot
pressure that puts patients at high risk

In a normal foot, the peak pressure in the forefoot while

walking is 600 kilo Pascals. At 15 Kpa, the arteries
carrying blood at 120 mm of Hg are blocked and the
capi.llaries are blocked at 6 Kpa. Boulton et al. The Foot 1990
 HIGH FOOT PRESSURES
NEUROPATHY, FOOT DEFORMITY

Hallux valgus, Claw toes, Limited joint

mobility,collapse of the lateral and medial and
transverse arches of the foot, & collapse of the midfoot
with a rockerbottom deformity contribute to high foot
pressures leading to ulceration.
 A V shunting in the foot
The arterioles in the foot which supply the dermal capillaries of the sole
are connected to small veins and venules by arteriovenous shunts. These
AV shunts are normally kept closed by sympathetic activity. These get
opened up in a diabetic foot due to decreased sympathetic activity and
. oxygenated blood is shunted from the arterioles to the veins,
hence
bypassing the skin.
Also this is why a diabetic foot bleeds profusely during slough cutting,
but looks pale on the next day.
High plantar pressure while walking, increases this anoxia, stimulating
inflammation and later ulceration, and then infection.
 “hot spots for
ulcer formation”

Illustration of Ulcer Formation

Various Foot Deformities with Potential for Ulcer
Formation
MECHANISM OF DIABETIC
FOOT ULCER

ROLE OF
HALLUX
RIGIDUS AND
SUBCUT.PAD OF
FAT

From Diabetic Foot by Levin

 TYPES OF INJURIES IN
DIABETIC FOOT
• SHOE BITE
• HOME SURGERY
• INSECT/RAT BITE
• THERMAL INJURY
• FOREIGN BODY INJURY
• VIGOROUS MASSAGE
• CHEMICAL INJURY

• PRESSURE INJURY
 Clinical Tests for
Neurological Assessment
 Vascular Assessment

Palpation of pulses

Ankle Brachial Index =

systolic BP in ankle ⁄
systolic BP in arm
 Vascular Assessment and
revascularisation
Vascular grafts

Ankle Brachial Index =

systolic BP in ankle ⁄
systolic BP in arm ; if
less than 0.7
 Investigations
Functions Investigations

Sensory Biothesiometry

Foot structure & Pedobarography

biomechanics

Skin Oxygen tension

FOOT SCAN SYSTEM
PAEDOPODOGRAM
 Investigations
Functions Investigations

Motor Electrophysio-
logical testing

Foot structure & X-ray,

biomechanics Foot Pressure

Skin Duplex, ABI

 Good Wound Care
The treatment is largely determined by:
• Off loading
• Debridement
• Moist dressing
• Control of infection (when required)

Tight blood glucose control is a important factor

 Off-Loading
‘Avoidance of all mechanical stress
on the injured extremity, while
maintaining necessary ambulation’
The strategies include application of:
• Total Contact Cast (TCC)
• Other casts/boots, surgical
shoes
• Half shoes, sandals, and felted
foam dressings.
• IF OFF LOADING OF THE
AFFECTED FOOT IS NOT DONE
THEN PATIENT

WALKS TO DEATH
 Debridement
The removal of necrotic and
senescent tissue as well as
foreign and infected material
from the wound.

Sharp debridement is
essential part of ulcer
therapy
THOROUGH DEBRIDMENT
most important step to promote healing

Diabetes Med. 1984

DIABETIC FOOT LESIONS
ARE LIKE

ICEBERG
ONLY SMALL PART IS VISIBLE
SURFICAL TREATMENT OF
DIABETIC FOOT

CENTRAL
PLANTAR
SPACE
ABCESS
SURGICAL TREATMENT
OF DIABETIC FOOT
CENTRAL
PLANTAR
SPACE ABCESS
AFTER TO TSL
DEROOFING
ICEBERG
PHENOMENON
SURGICAL TREATMENT
OF DIABETIC FOOT
CENTRAL
PLANTAR
SPACE
ABCESS
PRE
OPERATIVE
SURGICAL TREATMENT OF
DIABETIC FOOT
CENTRAL
PLANTAR
SPACE ABCESS
AFTER TOTAL
DEROOFING
ICE BERG
PHENOMENON
SURGICAL TREATMENT
OF DIABETIC FOOT

NECROTISING
FASCITIS
PRE
OPERATIVE
 SURGICAL TREATMENT
OF DIABETIC FOOT
• NECROTISING
FASCITIS
AFTER TOTAL
DEROOFING
ICEBERG
PHENOMENON
From Diabetic Foot by Levin
 CAUSES OF DELAYED/NON
HEALING IN DIABETIC FOOT

PRIMARY CAUSES
• INADEQUATE OFF LOADING
• INCORRECT VASCULAR
ASSESSMENT
• INADEQUATE PRELIMINARY
DEBRIDEMENT
 CAUSES OF DELAYED/NON
HEALING IN DIABETIC FOOT
SECONDARY CAUSES
• INADEQUATE ANTIBIOTIC
THERAPY
• NEPHROPATHY
• DRUGS
• INCORRECT METHOD OF
DRESSING
 AGENTS THAT DELAY
WOUND HEALING IN
DIABETES
 CORTICOSTEROIDS
NITROFURANTOIN
LIQUID DETERGENTS
NEOMYCIN SULPHATE
AGENTS THAT DELAY WOUND
HEALING IN DIABETES

CHLORHEXIDINE 2%
POVIDONE IODINE 10%
EUSOL SOLUTION
HYDROGEN PEROXIDE
 PRINCIPLES OF DRESSING IN
DIABETIC FOOT WOUNDS
• MAINTAIN MOIST ENVIRONMENT
• NON ADEHERENT
• ABSORBABLE
• EASY TO USE MATERIAL
• COST EFFECTIVE
• PROMOTES HEALING
• REDUCES COLONISATION OF BACTERIA.
 Moist Wound Dressing
• It prevents tissue dehydration
(preserving the viability and proliferative potential).
• Increases breakdown of dead tissue and fibrin
contributing to autolytic debridement.
• Potentiates interaction of growth factors with their
target cells
• Reduces the incidence of infection.
• Associated with less pain.
 Role of various
growth factors
in wound healing
 Growth factors
Growth factors of significance in wound healing are:
 Platelet Derived Growth Factor (PDGF)
 Vascular Endothelial Growth Factor (VEGF)
 Transforming Growth Factor- β (TGF- β)
 Keratinocyte Growth Factor (KGF)
 Epidermal Growth Factor (EGF)
 TGF-α
TGF-β
VEGF

PDGF-BB IGF
TGF-β
KGF TGF-β
VEGF PDGF-BB

TGF-β
Multiple Growth Factors are Expressed
Temporally in Human Wound Fluid

PDGF
bFGF
VEGF
TGF-
 Diabetic foot lesion
Cause of reduced expression
of growth factors & receptors
• Repeated trauma
in Diabetic Foot Ulcers
• Cell detritus/cell-fragments

• Increased & Prolonged

inflammatory response Increased activation of
macrophages by cytokines and TNF-α; IL-1β
• Increased invasion of
macrophages & neutrophiles growth factors

Fibroblasts &
inflammatory cells

Degradation of growth
factors & receptors Serin-proteases MMPs TIMPs

Chronification of Diabetic foot ulcers

Diabetologia. 2002 Jul;45(7):1011-6. Epub 2002 May 25
The only growth factors available
commercially, for the treatment of
diabetic foot ulcers are
recombinant human Platelet
Derived Growth Factor (rhPDGF)
& Epidermal Growth Factor
 Biology
• Platelet Derived Growth Factor is structurally a 25 kDa
protein
• It is released during stages of wound healing by
 Platelets
 Macrophages
 Fibroblasts
 Endothelial cells
 Keratinocytes
 PDGF and Receptors
• PDGF represents a
family of growth factors
consisting of 2 poly
peptide chains (A & B)
which forms the dimer
(protein pairs).
 PDGF-AA
 PDGF-AB
 PDGF-BB
• The PDGF receptor
has a trans-membrane
structure with
extracellular ligand-
binding domains and
intracellular tyrosine
kinase domains.
• Two PDGF receptors
exist, R-α and R-β,
with each possessing
different specificities
for their ligands.
 • PDGF-BB can activate
any PDGF receptor;
therefore its
therapeutic application
can activate any
configurations of it’s
receptors.
• The proliferation rate
of wound fibroblasts
was higher by PDGF-
BB than PDGF-AB
and -AA.*

* Biochem Biophys Res Commun. 1995 Apr 17;209(2):393-9.

 rhPDGF-BB
• Recombinant human Platelet Derived Growth Factor
(rhPDGF-BB) is a homo-dimer produced by Recombinant
DNA technology by inserting the human gene of
PDGF-BB in E. coli.
• Can also be produced with Yeast (Saccharomyces
cerevisiae).
• The biological activity of rhPDGF-BB is similar to that of
naturally occurring PDGF.
 Structure of rhPDGF-BB
Structure of PDGF-BB
Monomers
(depicted in green and blue)
 Role of PDGF-BB
in wound healing process
 PDGF is released by Platelets & Macrophages

Expert Opin.Biol Ther. (2002) 2(2):211-218

PDGF is released by Fibroblasts
 PDGF is released by Endothelial Cells & Keratinocytes

* Adapted from 1.Supplement of Podiatry Today, October 2003. 2. Diabetes Care, vol, no.2, no.2, 17-23. 4.Diabetes Care August 1999, 22:8;1,354-60
PDGF Action at Cellular Level
 Angiogenesis with PDGF-BB
1) Binds to its receptor on
vascular endothelial cell. 1
3
2) Inducing production of other 2
growth factors (VEGF)
3) Activates intracellular signal
4
transduction pathways

4) Stimulates endothelial proliferation 5

7
5) Promotes endothelial migration
6
6) Facilitates vascular tube formation

7) Recruits smooth muscle cells and

pericytes to stabilize the newly formed
vasculature
Summary of MOA of PDGF-BB
• Chemoattraction for neutrophils, monocytes &
fibroblasts.
• Mitogenic for smooth muscle cells and fibroblasts.
• Stimulates endothelial cells proliferation & migration.
• Promotes vascular tube formation.
• Stimulates epithelialization.
• Induces the release of other growth factors.
PDGF IN DIABETIC FOOT
WOUNDS

15 DAYS AFTER
PDGF USE
 COST EFFECTIVENESS OF BECAPLERMIN
FOR NONHEALING NEUROPATHIC
DIABETIC FOOT ULCERS
Milcovich et al Ostotomy wound manage 2003 nov;49
• 251 PEOPLE WITH DIABETES (124 PGDF/ 127
CONTROL)
• INCOPORATING PGDF RESULTED 26
FEWER ULCER DAYS PER PATIENT YEAR
COMPARED TO CONTROL
• INCREMENTAL COST EFFECTIVENESS
RATIO OF $6 PER ULCER DAY AVERTED
 Indication
Indicated for the treatment of lower extremity diabetic
neuropathic ulcers* that extend into the subcutaneous
tissue or beyond and have an adequate blood supply,
*(Stage III & Stage IV ulcers IAET Staging
classification)
Good wound care & tight blood glucose control are
very important in rhPDGF-BB therapy.
 Method of application
• One tube for one patient
• Proper hand wash before application.
• Tip of the tube should not come into contact with
the ulcer or any other surface.

• Before each application, the ulcer should be gently

rinsed with saline or water to remove any residual gel
and wound area cleaned.
• Applied once a day in a carefully measured quantity
adjusted according to the size of ulcers.
• Calculated dose of gel should be squeezed out onto a
clean, firm, non-absorbable surface (e.g. wax paper) in
a linear fashion.
• Use clean application aid (Cotton swab, tongue
depressor, etc )
• Measured quantity of gel should be spread evenly over
the ulcerated area including the margins to yield a thin
continuous layer of ~ 1.5 mm thickness.
• Gel should be covered with saline moistened gauze.
 (Contd…)

Algorithm for use of platelet derived growth factor (PDGF)

in treatment of diabetic foot ulcer
Algorithm for use of platelet derived growth factor (PDGF)
in treatment of diabetic foot ulcer (contd)
 WHY FOOT NEEDS TO BE
SAVED IN DIABETES?
• BK AMPUTATION REQUIRES 40% MORE
KCAL/MIN
• NET OXYGEN CONSUMPTION
INCREASES
• NEEDS 5 -10 % EXTRA CARDIAC
RESERVE
• 85% MORTALITY AT THE END OF 5
YEARS
DEFORMED FOOT WITH
GOOD FOOWEAR IS
PREFERABLE TO
AMPUTED LEG WITH
SOPHISTICATED
PROSTHESIS
DEFORMED BUT “WALKABLE”
DIABETIC FOOT
 An ancient Sanskrit saying.
“The one who walks, his good fortune also marches ahead.”

PRESERVE &
PROTECT THEM