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 Functional
and Aesthetic
Reconstruction
of Burned
Patients

DK3119_FM.indd 1 6/22/05 2:26:38 PM

Process Cyan Process Magenta Process Yellow Process Black
 Functional
and Aesthetic
Reconstruction
of Burned
Patients

Edited by
Robert L. McCauley, MD, FACS
University of Texas Medical Branch
Shriner’s Hospital for Children—Galveston Unit
Galveston, Texas, U.S.A.

DK3119_FM.indd 2 6/22/05 2:26:39 PM

Process Cyan Process Magenta Process Yellow Process Black
Published in 2005 by
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742

© 2005 by Taylor & Francis Group, LLC

No claim to original U.S. Government works

Printed in the United States of America on acid-free paper
10 9 8 7 6 5 4 3 2 1

International Standard Book Number-10: 0-8247-2583-2 (Hardcover)

International Standard Book Number-13: 978-0-8247-2583-9 (Hardcover)

This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted with permission, and sources are
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publisher cannot assume responsibility for the validity of all materials or for the consequences of their use.

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 In Loving Memory
This book is dedicated to the memory of my mother and father, Hattie and Willie McCauley,
who built a well of inspiration and support so deep that I continue
to drink from it each and every day.
Preface

Over the past two decades, advances in the management of the acute burned patients have resulted in the routine survival of
patients with 80 –90% total body surface area burns. Needless to say, the reconstructive needs of these patients are numer-
ous. This book addresses the reconstructive problems encountered in burn survivors by reviewing principles of wound
healing, prioritizing their reconstructive needs and categorizing the multitude of techniques available to plastic surgeons
for reconstruction. Surgical as well as non-surgical methods for improving the appearance and function are brought to
the forefront.
This text, Functional and Aesthetic Reconstruction of Burned Patients, systematically dissects problems associated with
burns of the head and neck, burns of the torso, perineum and upper extremity and burns of the lower extremities and feet.
The indications for various reconstructive procedures such as grafts, flaps, tissue expansion, and microvascular free tissue
transfers are incorporated throughout the text. The advantages and limitations of these techniques are thoroughly discussed.
In addition, the application of certain principles of aesthetic surgery are applied to these patients. Regardless of the extent of
the burn injury, wound closure is simply not enough. Today, as reconstructive surgeons, we must strive not only for function
but also for the aesthetic restoration of our patients. The reintegration of burn patients back into society as productive
members, in many ways, is dependent upon the restoration of form and function.
I would like to thank all the contributors to this book for their dedication and hard work. The secretaries in the
Medical Staff Office, the Graphic Arts Department as well as the Medical Records Department at the Shriners Hospital
for Children—Galveston Unit, all deserve a special thanks for their unyielding support in the completion of this project.

Robert L. McCauley

v
Contents

Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi
1. Properties of the Skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
John D. Bauer
2. Wound Healing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Michael K. Obeng, Linda G. Phillips
3. Principles in Management of Acute Burns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Steven E. Wolf, David N. Herndon
4. Management of Electrical Injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
Hazel Joseph, Robert L. McCauley
5. Chemical Burns: Small Burns with Severe Consequences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
David G. Greenhalgh
6. Reconstructive Needs of the Burn Patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
W. John Kitzmiller, Robert L. McCauley
7. Anesthesia for Reconstructive Burn Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85
Lee C. Woodson, Edward R. Sherwood , Joaquin Cortiella, Lynn Peterson
8. Skin Grafts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105
Prema Dhanraj, Robert L. McCauley
9. Skin Substitutes: Theoretical and Developmental Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Steven T. Boyce, Dorothy M. Supp
10. Microsurgical Free Tissue Transfer in Burn Reconstruction: Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
Fu-Chan Wei, Tewodros M. Gedebou
11. Principles of Tissue Expansion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
Robert L. McCauley, Michael K. Obeng
12. Management of Pigmentation Changes in Burn Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
Prema Dhanraj, Robert L. McCauley

vii
viii Contents

13. The Etiology and Management of Hypertrophic Scars and Keloids Following Thermal Injury . . . . . . . . . . . 173
Edward E. Tredget, Paul G. Scott, Aziz Ghahary
14. Lasers in the Treatment of Postburn Scars . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
Angelo Capozzi, Hugh L. Vu, Albert K. Oh, Suzanne L. Kilmer
15. Evaluation of the Burned Face . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 205
Marc Funke, Marcus Spies, Peter M. Vogt
16. Reconstruction of the Burned Scalp . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217
Enrique Garavito, Robert L. McCauley, Jacobo Verbitzky
17. Burns of the Skull and Scalp and Their Clinical Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
Mutaz B. Habal
18. Role of Micrografts and Minigrafts in Burn Reconstruction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233
Alfonso Barrera
19. Reconstruction of Burned Eyelids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
Brian Wong, Robert L. McCauley
20. Reconstruction of Cheek Deformities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
Robert L. McCauley, Michael K. Obeng
21. Reconstruction of the Burned Nose . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
Malachy E. Asuku, Robert L. McCauley
22. Reconstruction of the Burned Ear . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
Evan Pickus, Robert L. McCauley
23. Reconstruction of the Upper Lip and Commissure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319
Robert L. McCauley, Garry W. Killyon
24. Reconstruction of the Lower Lip and Chin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331
Robert L. McCauley
25. Correction of Cervical Burn Scar Contractures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 347
Robert L. McCauley
26. Correction of Soft Tissue Defects of the Back and Shoulders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359
Nelson Sarto Piccolo
27. Reconstruction of Axillary Contracture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367
Jui-Yung Yang
28. Reconstruction of the Burned Breast and Nipple– Areolar Complex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379
Robert L. McCauley, Garry W. Killyon, Kanika Bowen
29. Reconstruction of Chest Contractures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 393
Jui-Yung Yang
30. Reconstruction of Truncal Burns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 411
Nelson Sarto Piccolo
31. Reconstruction of the Perineum and Genitalia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 417
Lawrence J. Gottlieb, Mark A. Grevious
32. Management of the Acutely Burned Hand . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425
Robert L. Sheridan
33. Reconstruction of the Burned Hand . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 437
Malachy E. Asuku, Robert L. McCauley, Rocco C. Piazza II
34. Finger Lengthening of the Burned Hand by Distraction Osteosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463
David Wainwright, Donald H. Parks
Contents ix

35. Thumb and Finger Reconstruction by Microvascular Free Tissue Transfer . . . . . . . . . . . . . . . . . . . . . . . . . . 475
Fu-Chan Wei, Tewodros M. Gedebou
36. Rehabilitation of the Burned Hand . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489
Michael Serghiou, Alex McLaughlin
37. Reconstruction of Burn Deformities of the Lower Extremity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 521
Robert L. McCauley, Malachy E. Asuku
38. Reconstruction of Burn Scar Contractures of Feet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 549
Prema Dhanraj, Malachy E. Asuku, Robert L. McCauley
39. The Role of External Fixators in the Correction of the Equinovarus Deformities in Burn Patients . . . . . . . . . 563
Jason H. Calhoun, Kelly D. Carmichael, Debra Benjamin
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 571
Contributors

Malachy E. Asuku, MD, FWACS Department of Plastic and Reconstructive Surgery, Ahmadu Bello University
Teaching Hospital, Kaduna, Nigeria
Alfonso Barrera, MD, FACS Department of Plastic Surgery, Baylor College of Medicine, Houston, Texas, USA
John D. Bauer, MD Department of Surgery, University of Texas Medical Branch, Galveston, Texas, USA
Debra Benjamin, RN Division of Clinical Research, Shriners Hospital for Children, Galveston, Texas, USA
Kanika Bowen, BS University of Texas Medical Branch School of Medicine, Galveston, Texas, USA
Steven T. Boyce, PhD Department of Surgery, University of Cincinnati, Cinicinnati, and Shriners Burn Hospital,
Cincinnati, Ohio, USA
Jason H. Calhoun, MD Department of Orthopedic Surgery, University of Missouri – Columbia, Columbia,
Missouri, USA
Angelo Capozzi, MD, FACS Division of Plastic and Reconstructive Surgery, Shriners Hospital for Children,
Sacramento, and University of California, Davis, California, USA
Kelly D. Carmichael, MD Department of Orthopedics and Rehabilitation, University of Texas Medical Branch,
Galveston, Texas, USA
Joaquin Cortiella, MD Department of Anesthesiology, Shriners Hospital for Children, Galveston, and University of
Texas Medical Branch, Galveston, Texas, USA
Prema Dhanraj, MD Department of Plastic Surgery, Christian Medical College & Hospital, Vellore, Tamil Nadu, India
Marc Funke, MD Department of Plastic, Hand and Reconstructive Surgery, Medizinische Hochschule Hannover,
Hannover, Germany
Enrique Garavito, MD Department of Surgery, Shriners Hospital for Children, Mexico Unit and School of Medicine,
Anahuac University, Mexico, Mexico
Tewodros M. Gedebou, MD Department of Plastic and Reconstructive Surgery, Chang Gung University and Medical
College, Taipei, Taiwan
Aziz Ghahary, PhD Department of Surgery, University of Alberta, Edmonton, Alberta, Canada

xi
xii Contributors

Lawrence J. Gottlieb, MD Department of Surgery, University of Chicago, Chicago, Illinois, USA

David G. Greenhalgh, MD Department of Surgery, University of California, Davis, California, USA
Mark A. Grevious, MD Department of Plastic Surgery, University of Illinois, Chicago, Illinois, USA
Mutaz B. Habal, MD, FAAP, FRCSC, FACS Tampa Bay Craniofacial Center, Tampa, Florida, USA
David N. Herndon, MD Department of Surgery and Pediatrics, University of Texas Medical Branch and Shriners Burn
Hospital, Galveston, Texas, USA
Hazel Joseph, MD Department of Surgery, Eastern Virginia Medical School, Norfolk, Virginia, USA
Garry W. Killyon, MD, DDS Department of Surgery, Division of Plastic Surgery, University of Texas Medical Branch
and Section of Plastic and Reconstructive Surgery, Shriners Hospital for Children—Galveston Unit, Galveston, Texas, USA
Suzanne L. Kilmer, MD Shriners Hospital for Children, Sacramento, and Department of Surgery, University of
California, Davis, California, USA
W. John Kitzmiller, MD Division of Plastic, Reconstructive and Hand Surgery, University of Cincinnati Medical
Center, Cincinnati, Ohio, USA
Robert L. McCauley, MD Department of Surgery and Pediatrics, Division of Plastic Surgery, University of Texas
Medical Branch and Section of Plastic and Reconstructive Surgery, Shriners Hospital for Children—Galveston Unit,
Galveston, Texas, USA
Alex McLaughlin, OTR Department of Rehabilitation Services, Shriners Hospital for Children, Galveston, Texas, USA
Michael K. Obeng, MD Division of Plastic Surgery, University of Texas Medical Branch, Galveston, Texas, USA
Albert K. Oh, MD Shriners Hospital for Children, Sacramento, and University of California, Davis, California, USA
Donald H. Parks, MD Department of Plastic and Reconstructive Surgery, University of Texas—Houston Medical
School, Houston, Texas, USA
Lynn Peterson, CRNA Department of Anesthesiology, Shriners Hospitals for Children, Galveston, and University of
Texas Medical Branch, Galveston, Texas, USA
Linda G. Phillips, MD Department of Surgery, University of Texas Medical Branch, Galveston, Texas, USA
Nelson Sarto Piccolo, MD Instituto Nelson Picolo and Pronto Socorro para Queimaduras, Goiânia, Goiás, Brazil
Rocco C. Piazza II, BS University of Texas Medical Branch School of Medicine, Galveston, Texas, USA
Evan Pickus, MD Section of Plastic and Reconstructive Surgery, Shriners Hospital for Children—Galveston Unit,
Galveston, Texas, USA
Paul G. Scott, PhD Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada
Michael Serghiou, OTR Department of Rehabilitation Services, Shriners Hospital for Children, Galveston, Texas, USA
Robert L. Sheridan, MD Shriners Hospital for Children and Department of Surgery, Massachusetts General Hospital,
Boston, Massachusetts, USA
Edward R. Sherwood, MD, PhD Department of Anesthesiology, Shriners Hospital for Children, Galveston, and
University of Texas Medical Branch, Galveston, Texas, USA
Marcus Spies, MD Department of Plastic, Hand and Reconstructive Surgery, Medizinische Hochschule Hannover,
Hannover, Germany
Dorothy M. Supp, PhD Department of Surgery, University of Cincinnati, Cincinnati, and Shriners Burn Hospital,
Cincinnati, Ohio, USA
Edward E. Tredget, MD, MSc, FRCS Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
Jacobo Verbitzky, MD Division of Plastic Surgery, Shriners Hospital for Children, Mexico Unit, Mexico
Contributors xiii

Peter M. Vogt, MD Department of Plastic, Hand and Reconstructive Surgery, Medizinische Hochschule Hannover,
Hannover, Germany
Hugh L. Vu, MD, MPH Shriners Hospital for Children, Sacramento, and University of California, Davis,
California, USA
David Wainwright, MD Department of Plastic and Reconstructive Surgery, University of Texas—Houston
Medical School, Houston, Texas, USA
Fu-Chan Wei, MD, FACS Department of Plastic and Reconstructive Surgery, Chang Gung University and Medical
College, Taipei, Taiwan
Lee C. Woodson, MD, PhD Department of Anesthesiology, Shriners Hospital for Children, Galveston, and University of
Texas Medical Branch, Galveston, Texas, USA
Steven E. Wolf, MD Department of Surgery, University of Texas Medical Branch and Shriners Burn Hospital,
Galveston, Texas, USA
Brian Wong, MD Department of Ophthalmology, University of Texas Medical Branch, Galveston, Texas, USA
Jui-Yung Yang, MD Department of Plastic Surgery, Chang Gung Memorial Hospital, Taipei, Taiwan
1
Properties of the Skin

JOHN D. BAUER
University of Texas Medical Branch, Galveston, Texas, USA

I. Introduction 1 14. Cells of the Dermis 8

A. Anatomy 2 15. Glands 8
1. Gross 2 16. Hair 10
2. Epidermis 2 17. Blood Supply 12
3. Basement Membrane 3 18. Nerves 14
4. Stratum Spinosum 3 19. Skin as a Flexible Organ 15
5. Stratum Granulosum 4 20. Extensibility vs. Elasticity 15
6. Transitional Zone 4 21. Viscoelasticity 16
7. Stratum Corneum 4 22. Tissue Expansion 16
8. Cells of the Epidermis 4 23. Scar 18
9. Dermis 5 24. Special Cases 19
10. Structure 5 25. Photodamage 19
11. Collagen 6 26. Intrinsic Aging 20
12. Elastin 7 References 21
13. Ground Substance 8

I. INTRODUCTION barrier against assaults from bacteria, fungi, and viruses.

Melanocytes allow for a response to solar radiation with
Skin is the outer structural element, which contains an a protective change in color. Sensory nerves allow with-
organism’s component parts, thereby differentiating it drawal from extremes of heat and cold, and distinguish
from the surrounding environment. From the point of sharp and vibratory sensations. Skin has adapted to the
view of mammals, and other warm-blooded creatures, various environments to which it is exposed. Hence, the
the skin acts in many other capacities beyond simple con- glabrous skin of the hand lets a construction worker
tainment. In humans, it is the largest organ in the body, maintain a grip on a 9 lb hammer, while its more flexible
making up 16% of its weight. Grossly it is a major ther- counterpart over the leg will allow the muscles of a
moregulatory organ along with its sensory, metabolic, world-class sprinter to glide, expand, and contract. Sweat
immune, and protective qualities. Specifically, the acellu- glands act like a swap cooler taking advantage of evapo-
lar cornified exterior protects from abrasive and chemical ration to help regulate the temperature of humans who
trauma. Collagen confers resistance to mechanical force, have comparably little hair, as compared to fur-bearing
and elastin allows skin to shrink, expand, and snap creatures who thermoregulate through their pulmonary
back. The resident immune system affords an effective system.

1
2 Functional and Aesthetic Reconstruction of Burned Patients

As mentioned, skin has been described as an organ, keratinocytes, melanocytes, Langerhans cells, and
which is essentially a group of differentiated cells acting Merkel cells. The much thicker dermis below contains
in concert to carry out some identifiable function(s). The structural components like collagen and elastin, as well
focus of this chapter will be to review the gross and mol- as appendages like hair, sweat, eccrine, and sebaceous
ecular anatomy of skin; address biomechanics of aging and glands, as well as nerve endings.
scarring; as well as explore iatrogenic alterations of skin
like tissue expansion.
2. Epidermis
A. Anatomy The epidermis is the outer insensate, nonvascular layer
with a rapidly dividing basal layer consisting mostly of
1. Gross
mitotically active keratinocytes, which undergo a
As alluded to earlier, the skin acts as a protective covering to process of cornification. These cells progressively differ-
the body and is by weight the largest organ in the body. Its entiate as they are carried through the spinous, granular,
thickness and color vary by site. Whereas the skin on and cornified layers. Migration from the basal layer to
the back is thick, the skin on the eyelids can be as thin as the cornified layer takes about 28 days, and consists of
5/1000 of an inch. Clinically, these differences play a signifi- a well-defined, genetically programmed series of steps.
cant role in the planning of surgery from acquisition of skin The process begins with rapid division of mitotically
grafts to the planning, placement, and effectiveness of flaps. active basal keratinocytes followed by a cessation of div-
Color variations over the surface of an individual, with pro- ision, production of keratin and other proteins involved in
gressive lightening from head to toe, make the proper choice cross-linking, which leads to an increase in cell size.
of a donor site for the patient with an open wound essential. Next, a genetic and cellular reorganization occurs where
As can be seen in Fig. 1.1, skin is bilayered with a thin, intracellular organelles are lost and new proteins are pro-
rapidly replicating outer layer (epidermis), containing duced in anticipation of apoptotic death and dehydration

Figure 1.1 Normal skin anatomy. (With permission from Ross MH, Reith EJ, Romrell LJ. In: Kist K, ed. Histology: A Text and Atlas.
2nd ed. Baltimore: Williams & Wilkins, 1989:373.)
Properties of the Skin 3

(1 – 3). The thickness of the cornified layer can vary dras- (EGF), transforming growth factor alpha (TGF-a), and
tically depending on its location. Whereas the entire keratinocyte growth factor (KGF), as well as sterols like
thickness of the upper lid skin may be 5/1000 of an the retinoids, transit amplifying cells, are induced to go
inch, the skin on the back can be 10 times thicker through a series of genetically programmed divisions.
[Fig. 1.2(A) and (B)]. This provides an appropriate number of cells, which is fol-
lowed up by the postmitotic phase where growth factors
3. Basement Membrane like TGF-b signal cellular differentiation. The keratin
bundles in this layer are fine and flexible, which allows
This process begins at the basement membrane. There are
for cellular division. They are found in pairs, which are
three distinct types of keratinocytes in this basal layer:
specific to this layer, K5/K14. The bundles and the cells
stem cells, transit amplifying cells, and postmitotic cells.
themselves then undergo changes in shape, keratin type,
Stem cells comprise 10% of the cells in this area, and
as well as their interaction with desmosomes as they
can be identified by distinct b1 integrins (4). As they
pass into the spinous layer.
divide, one stem cell is left behind and the second daughter
begins the process of differentiation. Having this resident
4. Stratum Spinosum
population of undifferentiated cells is of interest because
these cells can accumulate mutations from assaults by The stratum spinosum is distinguished by its polyhedral
solar radiation and chemicals, which can lead to uncon- shape, basophilic cytoplasm caused by high levels of
trolled division, and/or skin cancers like squamous cell, RNA production, and large numbers of desmosomes.
or basal cell. Through a chorus of signals by the dermis, Though K5/K14 keratins persist, there is also a new form
several growth factors like epidermal growth factor of keratin, K1/K10. These pairs are stretched between

Figure 1.2 (A) Light micrograph showing the layers of thin human skin. (B) Light micrograph showing the layers of thick human skin.
(With permission from Ross MH, Reith EJ, Romrell LJ. In: Kist K, ed. Histology: A Text and Atlas. 2nd ed. Baltimore: Williams &
Wilkins, 1989:347 – 365.)
4 Functional and Aesthetic Reconstruction of Burned Patients

the nucleus and the desmosomes acting as intracellular communication is through growth factors like basic fibro-
bridges. As the keratinocytes move into the next transition, blast growth factor, endothelin-1, melanocyte stimulating
they enlarge and lamellar granules are formed in prep- hormone and stem cell factor (5,6). The density and
aration for the next phase. activity of these cells varies not only across races, and
individuals within these groups, but also within individ-
5. Stratum Granulosum uals. Importantly, three factors involved in the skin color-
ation are circulatory patterns, the number and activity of
In the stratum granulosum both proteolysis and phos-
melanocytes, and the thickness of the epidermis. With
phorylation of K1/K10 keratin pairs occur with the pro-
these in mind, it makes sense that skin color becomes
duction of new K2/K11 pairs. At the same time a series
lighter when moving from cranial to caudal. This
of proteins are produced which allow for the aggregation
obviously also plays a role in the choice of skin graft
and cross-linking of keratin. Further, the aforementioned
donor sites, as well as the transfer of soft tissue from
lamellar granules assemble in the cytoplasm and prepare
one area to another, when a choice exists. For instance,
to release a series of glycoproteins, glycolipids, phospho-
when transferring skin to the face, for color match, a
lipids, which are acted upon by resident enzymes that will
donor site above the cavical is preferred.
act to create a lipid barrier to skin permeation in the corni-
Lagerhan or dendritic cells are antigen-presenting
fied layer.
cells (Fig. 1.3), which exist in multiple tissues of the
body including skin, mucous membranes, lymph nodes,
6. Transitional Zone
thymus, and spleen. Their origin is the bone marrow,
Between the stratum granulosum and the stratum corneum and they then migrate to the suprabasement membrane.
lies a distinct transition zone. Here, the cells, which had TNF-a, IL-1b and the a6-integrin receptor are the induc-
been extremely metabolically active, now go through a tion signaling molecules (7). Transit through the basement
programmed cell death called apoptosis. Here, degradative membrane is accomplished with the expression of matrix
enzymes break down the cellular organelles, DNA frag- metaloprotease-9 (8), which helps to disrupt intracellular
mentation, and finally complete loss of the nucleus adhesions and degrades collagen IV. Once in position in
occurs. This leads us to the most superficial layer. the dermis, the immature dendritic cells endocytose bac-
teria that they encounter, move through the lymphatic
7. Stratum Corneum system, and in the maturing process, will present the bac-
terial cell antigens to T-cells in the local lymph node beds.
The stratum corneum cells are anucleate, dead cells, which
This is accomplished through three surface receptors:
provide the majority of the barrier function attributed to
MHC proteins which actually present antigens to the
the skin. As alluded to earlier, the keratin in these cellular
T-cell, costimulatory proteins involved in cell recognition,
remnants is cross-linked by strong disulfide bonds and
and adhesion molecules which maintain cell-to-cell
their surfaces are protected by lipid rich lamellae. The
contact. Like other cells formally known as clear cells,
thickness of this layer, unlike the other layers described,
dendritic cells cannot be visualized on routine stains, but
varies greatly and can go from only a few cell layers in
immunohistochemical visualization can be accomplished
the eyelid to tens of cells thick on the arms and legs. It
using the specific CD1a antibody (9).
gets even thicker on the back, and can be hundreds of
Merkel cells (Fig. 1.4) are found both in the epidermis
cell layers thick in the palms and soles.
and the dermis, and act as mechanoreceptors in the skin. In
the epidermis, through the production of nerve growth
8. Cells of the Epidermis
factor, they have been shown to function as mechano-
Though the vast majority of the cells in the epidermis are receptors (10). Though these cells appear to function in a
keratinocytes, there are three other notable residents neural capacity, studies on developing fetal skin have
involved in such varied functions as skin pigmentation suggested an epidermal origin (11). Their unique antibody
(melanocytes), antigen presentation (Langerhans cells), signature for the skin is cytokeratin-20. In the epidermis,
and neuroendocrine functions (Merkel cells). Melano- Merkel cells are joined to the keratinocytes by desmo-
cytes are the melanin producing cells, are of neural somes at epidermal ridges, and through microvilli at
crest origin, and, in the skin, are interspersed among the their cell surface respond to mechanical distortion. They
basal keratinocytes. Their molecular, antibody signatures are also localized around the arrector pili muscles in the
are S-100 and HMB-45. They transfer pigment via mela- hair follicles in the dermis, and probably play a role
nosomes to keratinocytes through dendritic processes, their activity (12). They have further been implicated in
and are stimulated to do so, for instance, by ultraviolet the development of eccrine sweat glands, the hair follicle,
radiation. It has been shown that melanosome regula- and nerves of the skin (13). Other neural elements exist
tion is intimately related to keratinocytes, and that the and will be covered later in the chapter.
Properties of the Skin 5

Figure 1.3 Light micrograph of Langerhan’s cell (dendritic). (With permission from Ross MH, Reith EJ, Romrell LJ. In: Kist K, ed.
Histology: A Text and Atlas. 2nd ed. Baltimore: Williams & Wilkins, 1989:347 – 365.)

9. Dermis 10. Structure

As described earlier, the dermis is a dynamic and variable Anatomically, the dermis has been divided into papillary
structure which functions in a number of ways depending and reticular portions, with a closely adjacent hypodermis.
on the location and physical demands of the structures The papillary dermis is the most superficial and is distin-
over which it lies. It needs to be very flexible and elastic guished by its dermal papillae which project upwardly
over structures, which need to expand and contract like and interdigitate with downwardly projecting rete pegs
the thorax, or the joints. It requires durability and must of the epidermis. It maintains small-diameter collagen,
maintain considerable tensile strength to survive the shear- the immature and highly distensible form of elastin
ing forces inflicted on hands and feet with manipulation of called oxytalan, has a large number of fibroblasts, and
objects, or ambulation. Thermoregulation, hydroregulation, provides nutrition to the avascular epidermis through
sensation, and olfactory stimulation are but a few of the capillaries which extend from the subpapillary plexus to
functions carried out by appendages found in the dermis. the edge of the basement membrane. Its most superficial
6 Functional and Aesthetic Reconstruction of Burned Patients

Figure 1.4 Electron micrograph of Merkel cell. Note contact with peripheral terminal neuron (NT). (Courtesy of Dr. B. Munger,
1984.) (With permission from Ross MH, Reith EJ, Romrell LJ. In: Kist K, ed. Histology: A Text and Atlas. 2nd ed. Baltimore: Williams
& Wilkins, 1989:347– 365.)

component is an area known as the compact zone or the will vary depending on the structural needs. Though 25 dis-
sublamina densa. Along with an abundance of extracellu- tinct a chains have been identified, allowing for literally
lar matrix adhesion molecules like tenacin, it also contains thousands of potential combinations, only 20 different col-
the ends of the anchoring fibrils of the epidermis made pri- lagen types have been identified (Table 1.1) (14).
marily of collagen VII. The reticular dermis is distin- The skin is composed primarily of the fibrillar form of
guished by much larger interdigitated bundles of collagens, namely I, III, IV, V, and VII. After secretion
collagen and elastin, giving the dermis its strength and into the extracellular matrix, these fibrils assemble into
resilience. The hypodermis is an adipose rich layer just strands between 10 and 300 nm in diameter, and up to
deep to the dermis which fills several essential roles. It hundreds of micrometers in length (Fig. 1.5). They then
serves to insulate the body, provides a ready reserve of can aggregate into larger bundles, or collagen fibers.
energy supply, and allows for mobility over structures Types I and III are the dominant forms in the skin, with a
like joints and most nonglabrous skin. It is mentioned ratio in normal skin of 4:1, though in injured skin this
here because it is intimately connected to the more ratio can be temporarily decreased to 2:1. Interestingly, in
fibrous reticular dermis by both vascular and neural scars this ratio tends never to return to normal in either
tissues, and further contains many of the skin appendages skin or fascia and has therefore been implicated in the
like hair follicles and sweat glands. development of incisional hernias (15). Further, multiple
studies have shown this decreased collagen I/III ratio in
hypertrophic scarring (16). Type V collagen, is found pri-
11. Collagen
marily in the papillary dermis, the matrix of the basement
The major structural component of the dermis is collagen. It membrane around blood vessels, nerves, and epidermal
makes up 25% of the protein mass in animal, and a full 70% appendages, where it combines with types I and III collagen
of the dry weight of skin. It has a triple helical structure, and is involved in regulating fibril diameter.
made of a chains rich in proline, lysine, and glycine, Collagen types IV and VII have been referred to as
which together create a tightly packed rope-like structure. network-forming. Type IV assembles into sheets resem-
This compact structure is stabilized by interaction between bling a meshwork which makes up the majority of the
glycine and the combination of both hydroxylated proline basement membrane of the epithelium, and type VII
and lysine. Both tensile strength and elasticity are the hall- forms into anchoring fibrils which act to secure the epi-
marks of this structural design, and as described above, thelial basement membrane to the dermis (17).
Properties of the Skin 7

Table 1.1 Some Types of Collagen and Their Properties

Type Molecular formula Polymerized form Tissue distribution

Fibril-forming I a1(I)2a2 (I) Fibril Bone, skin, tendons, ligaments, cornea,

(fibrillar) internal organs (account for 90% of
body collagen)
II [a1(II)]3 Fibril Cartilage, invertebral disk, notochord,
vitreous humor of the eye
III [a1(III)]3 Fibril Skin, blood vessels, internal organs
V [a1(V)]2a2(V) and Fibril (with type I) As for type I
a1(V)a2(V)a3(V)
XI a1(XI)a2(IX)a3(XI) Fibril (with type II) As for type II
Fibril-associated IX a1(IX)a2(IX)a3(IX) Lateral association with Cartilage
type II fibrils
XII [a1(XII)]3 Lateral association with Tendons, ligaments, some other tissues
some type I fibrils
Network-forming IV [a1(IV)]2a2(IV) Sheetlike network Basal lamina
VII [a1(VII)]3 Anchoring fibrils Beneath stratified squamous epithelia
Transmembrane XVII [a1(XVII)]3 Not known Hemidesmosomes
Others XVIII [a1(XVIII)]3 Not known Basal lamina around blood vessels
Note: Types I, IV, V, IX, and XI are each composed of two or three types of a chains, whereas types II, III, VII, XVII, and XVIII are composed of only one
type of a chain each. Only 11 types of collagen are shown, but about 20 types of collagen and bout 25 types of a chains have been identified so far.
Source: With permission from Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular Biology of the Cell. 4th ed. New York: Garland
Science-Taylor & Francis Group, 2002:1065– 1125.

12. Elastin Three forms of elstasic fibers have been defined. The
first and most superficial is Oxytalan (19). It is mostly
Elastin is the spring that allows skin which has been
microfibrils coated with soluble elastin. They are vertically
stretched or deformed to snap back into its original
oriented, flexible, and are considered the least mature of
shape (Fig. 1.6). This 350 kDa molecule (18) is extremely
the three forms. The second is Elaunin, considered the
distensible, though this capability is tempered by the rela-
tively nondistensible collagen with which it is interwoven
in the skin. Its precursor tropoelastin is secreted into the
extracellular matrix, where it then is linked to a pre-
existing scaffold of glycoproteins called microfibrils, the
most notable being fibrillin. It is assembled into sheets
and then takes its position in the dermis where it extends
from the lamina densa of the epidermal basement mem-
brane, through the entire dermis, to the hypodermis.

Figure 1.5 Electron micrograph of collagen fibril note striated Figure 1.6 Stretching a network of elastin molecules. Note
appearance. (Courtesy of Robert Horne.) (With permission from cross-linking covalent bonds. (With permission from Alberts B,
Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular
Molecular Biology of the Cell. 4th ed. New York: Garland Biology of the Cell. 4th ed. New York: Garland Science-Taylor
Science-Taylor & Francis Group, 2002:1065– 1125.) & Francis Group, 2002:1065 – 1125.)
8 Functional and Aesthetic Reconstruction of Burned Patients

intermediate form of the three with more cross-linked a major regulatory factor. Other cytokines shown to play
elastin fibrils. It is horizontally oriented and interdigitated a role are IL-1 and IL-8. Interferon gamma has been ident-
with oxytalan in the deep papillary and reticular dermis. ified as a potential downregulator (24). This is of particular
Finally, there is mature elastin, which lies deep in the reti- interest especially as it relates to abnormal scarring, where
cular dermis. It is the least flexible and is also horizontally fibroblast hyper-responsiveness to TGF-b has clearly been
oriented. As a side note, the failure of the skin to snap shown (23).
back, seen so often in sun damaged skin, has been linked Macrophages, along with shorter-lived neutrophils, are
to abnormal elastin produced after exposure to UV radi- the major phagocytic cells of the immune system. Both are
ation (20), and errors in elastin production are seen in dis- able to engulf microorganisms, and destroy them with
eases like Ehlers – Danlos syndrome (21). Further, lysosomal derived superoxide free radicals, hypochlorite,
breakdown of elastin has been shown to occur as skin and hydrolases. Unlike neutrophils, macrophages have a
ages, leading to laxity seen in the older population (22). much more prominent role in the skin’s immune system.
They originate from bone marrow-derived monocytes,
13. Ground Substance and convert to macrophages after entering the skin from
the vascular system. Along with the aforementioned, lyso-
Along with the fibrous and flexible portions of the dermis
somes/phagasomes have a well-developed rough endo-
are the skin’s shock absorbers. These are glycoproteins,
plasmic reticulum (Fig. 1.7), and Golgi apparatus for
primarily glycosaminoglycans (GAGs), covalently linked
protein production and intermediate filament system for
to proteoglycans. They tend to attract water and surround
mobility. Besides phagocytosis and lysis of microorgan-
the collagen and elastin, as a sort of gel or ground sub-
isms, they process and present antigens to T- and B-
stance. Dermal occupants known as fibroblasts produce
cells. In addition, these cells are secretory with production
them, and they help protect against compression injury
of growth factors and other cytokines. They are involved
and dermal deformation.
in coagulation, as well as wound healing. Dermal dendritic
GAGs are unbranched polysaccharide chains which are
cells, like the previously described Langerhans cells, are
highly anionic and hydrophilic. They therefore attract
also phagocytic, but are more involved in the transport,
positively charged ions like sodium, as well as large
processing, and presentation of antigens in the afferent
amounts of water, which helps produce the gel earlier.
loop of the immune system.
Some examples include hyaluronic acid, condroiton
sulfate/dermatin sulfate, heparin sulfate, and keratin
sulfate. Proteoglycans have a core polypeptide chain 15. Glands
with multiple sugar side chains, one of which by definition
Eccrine, apocrine, and sebaceous glands all reside in the
is a GAG. Some examples include hyaluronic acid, con-
dermis/hypodermis (Fig. 1.8). Eccrine or sweat glands
droiton sulfate/dermatin sulfate, heparin sulfate, and
have been described as the shower of the skin, and are
keratin sulfate. Other glycoproteins like fibronectin are
found in great numbers over the entire skin surface. Apoc-
intimately involved in cell – matrix adhesion through
rine glands are more localized to areas like the axilla and,
their interaction with the collagen, elastin, and integrins
groin. Compared to eccrine glands, they have a less well-
on the surface of fibroblasts.
defined physiological function, but are well known to be
responsible for the odor caused when the fats produced
14. Cells of the Dermis
by these glands are metabolized by resident bacteria.
By far, the predominant cell of the dermis is the fibroblast, The physiologic function of the sebaceous gland is even
though other less numerous monocytes like macrophages, less well defined, though phermonal and waterproofing
and dendritic cells, as well as mast cells, play a major role roles have been suggested.
in the immune, inflammatory, and allergic activities of the Eccrine sweat glands (Fig. 1.9) are thermoregulatory,
skin. Other transient visitors include lymphocytes and and act to control elevations in body temperature.
granulocytes/neutrophils. During extrinsic exposure to heat, intrinsic metabolic pro-
Fibroblasts, as stated, are the most populous cells in the duction of heat through exercise, and/or emotional stress,
dermis, and in uninjured skin exist in a senescent state. the release of water and electrolytes occur, producing
However, they are called into action after skin trauma, evaporative heat loss. Humans have, by far, the most
where they produce a variety of extracellular matrix pro- extensive eccrine sweat gland system in mammalian com-
teins including collagen, elastin, and glycoproteins. They munity. Interestingly, we are born with our full comp-
are also involved in the contraction of wounds and have lement of sweat glands at birth, so none are added as we
been termed myofibroblasts or activated as illustrated by grow. So at birth we have an eightfold higher density of
their production of smooth muscle actin-a (23). Trans- sweat glands compared to when we are adults. Further,
forming growth factor-b (TGF-b) has been identified as one of the denser areas of distribution is on the palms of
Properties of the Skin 9

Figure 1.7 Micrograph of macrophage. Note phagocytized particles. (With permission from Wheater PR, Burkitt GH, Daniels VG.
Connective tissue. In: Wheater PR, Burkitt GH, Daniels VG, eds. Functional Histology: A Text and Colour Atlas. New York: Churchill
Livingstone, 1987:52– 63.)

Figure 1.8 Skin and appendages. Note location of sebaceons and merocrine (eccrine) sweat glands. (With permission from
Wheater PR, Burkitt GH, Daniels VG. Skin. In: Wheater PR, Burkitt GH, Daniels VG, eds. Functional Histology: A Text and Colour
Atlas. New York: Churchill Livingstone, 1987:130 – 141.)
10 Functional and Aesthetic Reconstruction of Burned Patients

Figure 1.9 Merocrine (eccrine) sweat glands. Note pale string secretory cells. (With permission from Wheater PR, Burkitt GH,
Daniels VG. Skin. In: Wheater PR, Burkitt GH, Daniels VG, eds. Functional Histology: A Text and Colour Atlas. New York: Churchill
Livingstone, 1987:130 – 141.)

the hand, which provides a great benefit to us, since the open directly onto the surface of the skin around the
grasping and holding of objects is facilitated by moist skin. lips, from the buccal mucosa, the inner eyelids, labia
Numerically, there are between two and five million minora, and around the nipple, where they are referred
sweat glands on an average adult, and unlike apocrine to as free glands. In the fetus, they tend to be quite promi-
glands, they are not associated with hair follicles. They nent, secondary to maternal hormones, but they regress
are simple tubular glands with both ductal and secretory after birth until puberty, where they enlarge again second-
components. Eccrine sweat is clear and odorless and ary to intrinsic hormonal influences, and subsequently play
99% water, the other 1% being electrolytes and organic a significant role in the development of acne.
material. Its release is an active secretory process via a Histologically, the sebum producing cells in the gland
sodium, potassium, and chloride cotransport system. begin small with distinct lipid vacuoles, but they may
Apocrine glands are concentrated in the axillae, and increase to 100–150 times their original size as their vacu-
perineal areas (Fig. 1.10). They are coiled glands oles enlarge. In the latter stages, these lipid vacuoles may
embedded in the dermis, with a short duct, which in fact fuse, as cytoplasmic organelles break down, and
empties into the hair follicle just superficial to the sebac- lysosomal enzymes ultimately produce cellular disruption
eous duct in the pilo-sebaceous unit. Like sebaceous as the apoptotic genetic program unfolds. Sebum containing
glands, they are under adrenergic control, and their triglycerides, wax esters, squalene, cholesterol esters, and
output becomes active in adolescence, and decreases cholesterol, are then released into the lumen of the gland
slowly with age. The exact composition is unclear since along with keratinaceous squamae and bacteria. Hormonal
isolating this from eccrine sweat and sebum is difficult. activity is primarily from androgens (25), but influences,
Finally, sebaceous glands are the sebum producing either through exogenous or endogenous exposure, by estro-
glands found over the entire skin surface, except the gens, progestins, glucocorticoids, as well as thyroid and
palms, soles, and dorsum of the feet (Fig. 1.11). Like pituitary hormones that are under investigation.
hair, described later, they are unique to mammals. In
humans, the density and size of these glands varies
16. Hair
greatly with small single-celled glands on areas like the
eyelids, all the way to huge cauliflower-shaped glands The topic of hair is as variable as hair itself. This keratin
on the face, scalp, and ano-genital orifices. Most of the rich proteinaceous structure is peculiar to mammals. It
time they are associated with hair follicles, and the unit protects the skin from solar radiation, provides insulation,
is referred to as a pilo-sebaceous gland, but they can sweeps foreign bodies from the eyes, and may become
Properties of the Skin 11

Figure 1.10 Apocrine sweat glands. Note their highest density

in the axilla and groin. (With permission from Wheater PR,
Burkitt GH, Daniels VG. Skin. In: Wheater PR, Burkitt GH, Figure 1.11 Sebacious glands. Note the association with hair
Daniels VG, eds. Functional Histology: A Text and Colour follicles. (With permission from Wheater PR, Burkitt GH,
Atlas. New York: Churchill Livingstone, 1987:130 – 141.) Daniels VG. Skin. In: Wheater PR, Burkitt GH, Daniels VG,
eds. Functional Histology: A Text and Colour Atlas. New York:
Churchill Livingstone, 1987:130–141.)
erect in the face of fear or other types of arousal. The fol-
licle contains sebaceous and apocrine glands, which bathe
the skin with oils. Its color may be blond to black. Its formation, the papillary pore encasing the blood supply,
length may be nearly unlimited on the scalp, yet short on as well as epithelial cells involved in the actual formation
the eyelids. Its texture can be coarse in the axilla and of both the sheaths and hair itself. More superficially is the
fine on the helical rim. The shape and architecture (curly permanent portion, which contains a bulge, to which the
or straight) varies across individuals as well as within an arrector pilori muscles attach. Within this bulge are stem
individual. Its phases of growth, involution, and quies- cells believed to be involved in the regeneration of hair
cence provide a window into genetic cycling, stem cells, following the resting phase. The distalmost portion
and apoptosis. carries the hair to the surface, but also is home to the
The anatomic structure of the hair follicle has been well sebaceous and apocrine glands.
studied (Fig. 1.12). Most of the time it is embedded in the The cycle of hair growth has been broken into three dis-
dermis, although longer shafts can be located in the subcu- tinct phases: antigen, catagen, and telogen. The period
taneous fat in areas like the scalp. The follicles exit the during which the hair producing cells are active is
skin at an angle, which is significant when carrying out known as the antigen phase. The length of this phase is
reconstructive or aesthetic hair transplantation. The variable even within specific hair types like the scalp.
lower portion, or the base, contains the bulb, which has a The duration in the scalp is 2 –5 years, with a growth
dermal papilla containing specialized fibroblasts inti- rate of 0.35 mm per day. This variability is important,
mately involved in hair growth signaling and follicle as it ensures scalp coverage as the individual hairs cycle.
formation (26), dendritic melanocytes involved in color If each hair follicle’s antigen phase ended simultaneously,
12 Functional and Aesthetic Reconstruction of Burned Patients

Figure 1.12 Hair follicle. (With permission from Wheater PR, Burkitt GH, Daniels VG. Skin. In: Wheater PR, Burkitt GH,
Daniels VG, eds. Functional Histology: A Text and Colour Atlas. New York: Churchill Livingstone, 1987:130 – 141.)

areas of baldness would result. This can, and in fact, does out many other functions. Vasoconstriction/dilation of the
happen when follicles are traumatized. A good example is vasculature assists in thermoregulation. Endothelial cells in
hair transplantation, where a transient loss of all trans- the walls of blood vessels are a source and a target for
planted hair shafts often occurs, which must be carefully inflammatory cytokines, as well as the source of vasoactive
explained to patients. Other examples include fever molecules like nitric oxide. They are vital in activating the
stress, and some types of drugs. clotting cascade (31). The upregulation of selections, integ-
The catagen phase last only a few days. During this rins, and I-cams allows for cellular adhesion, demargina-
phase, mitotic activity ceases, the hair bulb and the prox- tion, and transmigration of leukocytes and monocytes,
imal, transient portion of the shaft involute, and the hair which is critical in the response to injury and wound
dies, though it may remain in place. The telogen phase is healing (32,33). Further, understanding the gross and
the time when no hair is produced by the follicle. The microscopic anatomy is essential in addressing tissue loss
remaining hair may remain in the shaft, but does not and reconstruction, especially as it relates to flap design.
grow. It may also be sluffed if appropriate mechanical As classically described, the blood supply to the skin
stress is applied. On the scalp, under normal circum- begins with segmental vessels, originating from the aorta,
stances, 10% of hairs are in telogen phase, at any which then branch into perforating vessels, which connects
one time. to the cutaneous vasculature (Fig. 1.13). The cutaneous
The regulation of these phases is under active investi- vasculature is then broken into two critical subgroups: the
gation, and along with the specialized fibroblasts of the musculocutaneous perforators and the direct cutaneous
dermal papilla described earlier, cytokines including vessels. These two subgroups then supply two horizontally
PDGF, TGF-B, and EGF have been implicated in both oriented plexuses, one at the junction of the dermis and the
stimulatory and inhibitory functions (27 – 29). The apopto- subcutaneous fat, and another at the papillary dermis, just
tic transition of the follicle from antigen to catagen and deep to the epidermis. These two systems are connected
finally to telogen appears to be at least partially regulated through multiple anastomoses. Finally, the superficial
by protooncogenes blc-2, c-myc, c-myb, and c-jun (27,30). plexus gives off dermal papillary loops, which are located
in the dermal papillae, directly opposed to the epidermal
rete pegs. Papillary loops approach as close as 1 mm to
17. Blood Supply
the basement membrane of the epidermis. This is where
The blood supply to the skin, along with the obvious func- nutrient and metabolic exchange occurs, for the otherwise
tion of providing nutritional and metabolic transport, carries nonvascularized epidermis.
Properties of the Skin 13

Figure 1.13 Skin circulation. Note the deep arterial and venous vessels giving way to branches progressing superficially to the two
superficial plexes. (With permission from Wheater PR, Burkitt GH, Daniels VG. Skin. In: Wheater PR, Burkitt GH, Daniels VG, eds.
Functional Histology: A Text and Colour Atlas. New York: Churchill Livingstone, 1987:130 – 141.)

The subgroups of the cutaneous vasculature men- When it was discovered that there were areas of the
tioned earlier, musculocutaneous perforators and direct skin, which were supplied by direct cutaneous or axial
cutaneous vessels require special consideration as they vessels, entire new flap strategies could be devised. This
relate to flap reconstruction. Prior to the development of concept of angiosomes (34) allowed not only for much
the concept of angiosomes, which supply an axial blood longer, thinner rotation, advancement, and interpolated
supply to an area of skin through direct cutaneous vessels, skin flaps, but also for the development of island flaps.
flaps were designed with the thought that the blood supply This is where an area of skin can be elevated with its
was random. In other words, it was thought that skin was axial vessels attached, completely free from its surround-
supplied through the musculocutaneous perforators, ing skin, and be moved and inset to an adjacent, but
which were perpendicularly oriented to the horizontally separate, area.
oriented deep and superficial plexuses. So, as one elevated When it comes to injuries to the skin, whether traumatic
a skin flap, the perpendicular connections were divided, or iatrogenic, the vascular tree plays an important role in
and the only blood supply to the tip of the flap was the healing. The process of re-establishing blood flow to the
nearest perpendicular perforators at the base. So, length- injured tissue is referred to as angiogenesis. When blood
to-width ratios and tube flap strategies were devised for vessels are disrupted, the normally quiescent endothelial
random flaps, which would provide the distalmost cells are activated and begin both dividing and migrating.
portion of the flap adequate musculocutaneous perforators The mechanisms by which these occur are under investi-
at the base to survive. This limited the flexibility of skin gation, and several key cytokines have been identified.
flaps, and often led to multi staged procedures. Unfortu- Vascular endothelial growth factor (VEGF) is produced
nately, flap morbidity was also all too common. locally by keratinocytes and several other cell types, and
14 Functional and Aesthetic Reconstruction of Burned Patients

has been shown to bind with tyrosine kinase receptors on distributed throughout the papillary dermis, skin appen-
the surface of endothelial cells initiating cellular division dages, and hair follicles. Interestingly, in areas where
(35). Proteolytic enzymes then begin to degrade the sur- fine discrimination is required, for example, in the finger-
rounding basement membrane and extracellular matrix tips, each nerve fiber may innervate a single dermal
releasing basic bFGF, and upregulating integrins and papilla. This leads to an axonal density as high as 1000
selectins, and VCAM-1, thereby allowing the endothelial axons per 1 square centimeter of skin surface, and rep-
cells to migrate toward the stimulus and carry out capillary resents rapidly adapting receptors (36). These C-fibers
tube formation. Actual vessel formation is accomplished account for the sensation of touch and temperature, and
also by the activation of resident pericytes, which form to some degree, pain and itch. But there is a group of myli-
chords. These chords then develop gaps through which nated sensory fibers, namely Ad-fibers which may play a
the sprouting endothelial cells migrate to form a lumen. significant role in pain and itch (37).
The newly formed vessels then extend into the injured There are several specialized structures in the skin
tissue and merge with established blood vessels as well involved in various aspects of sensation which merit
as with other newly formed vessels. Ultimately, this mention at this point. Merkel cells, as discussed earlier,
results in the development of a patent vascular system are structurally consistent with a neuroendocrine origin
with capillary loops, microvessels, and anastomoses and form cell – axon complexes with C-fibers mostly
between larger vessels, thus providing a blood supply for among the basal keratinocytes in the fingertips, lips, and
the healing wound. nailbeds. They form so called “touch spots,” and have
been implicated to function mostly as the slow adapting
mechanoreceptors of the skin. This slow response is
18. Nerves
responsible for both changing and static conditions and
In its capacity as a sense organ, this skin acts to protect us these continue to fire after the stimulus has ceased.
through the sensations of heat, cold, and pain, may stimu- Pacinian corpuscles are encapsulated receptors which
late us with sensations of light touch to irritating itch, as are multilayered and have an onion layered appearance
well as response to cold or fear, and goose bumps. All and consist of an outer perineural layer, and an inner
this is accomplished through a ubiquitous neural network structure with an axon surrounded by Schwann cells col-
carrying incoming and outgoing signals. Afferent lagen, elastin, and fibroblasts. Their greatest concen-
sensory nerves carry sensations of pain, touch, tempera- tration is in the palms and soles, and they have been
ture, and pressure to the CNS, where voluntary and invo- shown to act as a rapidly adapting mechanoreceptor and
luntary responses are formulated and effected. The respond to pressure while the skin is being indented. In
efferent autonomic system, on the other hand, responds other words, they only respond when the skin is being
to environmental stimuli with reactions like vasoconstric- deformed. Meisner’s corpuscles are located at the
tion/dilation, sweating, and inflammation. The organiz- dermal epidermal junction, and like the other specialized
ation of this system is varied and the density and type of cells listed, are primarily located on the palmar and
innervation is commensurate with the requirements of plantar skin. They are cylindrical in shape and have sup-
the tissue. porting structures consisting of modified Schwann cells,
Grossly, the sensory innervation to the skin is laid out in and an unmylinated afferent terminal, which responds to
strips known as dermatomes. These come from the dorsal touch.
and ventral rami of each spinal nerve. In the head and Finally, along with peptides like histamine, the nervous
neck, cranial nerves provide sensation, primarily through system of the skin has been shown to be intimately
the trigeminal nerve. In the hands, sensation is carried involved in the inflammatory process, as exemplified by
through the brachial plexus (C5 – T1), to the radial, the Triple response of Lewis. So, not only are the afferent
median, and unlar nerves. Specifically, cutaneous C-fibers responsible for responding to noxious stimuli with
braches of musculocutaneous nerves enter the subcu- sensation of pain, itch, warm, and cold, but they also can
taneous fat and then separate into a deep plexus which initiate a local inflammatory reaction. As the action poten-
innervates vascular and adnexal structures, and a super- tials are carried toward the CNS, upon arriving in the
ficial plexus which ascends to a plexus in the papillary spinal chord, an additional pathway is initiated whereby
dermis. The skin also has autonomic nerve fibers which retrograde antidromic impulses cause the release of neuro-
travel initially with the sensory fibers, but then branch peptides stored along the peripheral nerve. This produces
off to supply innervation to glands, blood vessels, and local erythema, followed by a wave of arterial vasodilata-
the tiny arrector pili muscles. tion extending beyond the area of injury (flare). Finally,
Microscopically, sensation to the skin is divided into increased permeability of venules results in plasma extra-
free and corpuscular components. Free nerve endings are vasation, influx of inflammatory cells, and wheal
primarily nonmylenated C-fibers, which are widely formation.
Properties of the Skin 15

19. Skin as a Flexible Organ

Though technology like electron microscopes, molecular
biology, and protein specific stains did not exist at the
time Karl Langer did his classic experiments on skin
tension and extensibility, simple observation of incised
skin gave clues to the structures which we now know
exist. An awl is not required to understand that these prop-
erties of the skin are urgently important, especially to the
plastic surgeon faced with traumatic soft tissue defects
requiring closure, or with iatrogenically produced defects
in the process of tumor excision. It is easy to see the differ-
ence between the rapid snap of the cheek of a baby
encountering the first contact with an overzealous aunt,
and the sluggish return to position of the lower lid of
that elderly aunt as she is examined for her first blepharo-
plasty. It is also clear that the inelastic, tension resistant
skin that we depend upon to help us grasp that valuable,
flower filled antique crystal vase, would not be very
useful situated on the elbow which we will flex to have a
satisfying floral whiff. So differences exist not only
between the skin of different individuals, but also
between the skin of a single individual. Further, these
properties can change when aging, exposure, trauma and
scarring, as well as location on the body vary. Finally,
these properties can be exploited when innovators like
Radovan, Argenta, and Austad see the opportunity to
stretch the skin when the scalp of a burned child needs
resurfacing.
Figure 1.14 (A) Typical stress –strain curve of human skin in
20. Extensibility vs. Elasticity tension. (With permission from Gibson T, Kenedi RM.) (B) The
stress relaxation that occurs in skin increases with the applied
Skin is not a rigid structure. It is flexible, albeit variably
load. (With permission from Gibson T, Kenedi RM. The struc-
between different areas in any one individual and
tural components of the dermis. In: Montagna W, Bentley JP,
between individuals, as described earlier. Skin’s ability Dobson RL, eds. The Dermis, 1970. Courtesy of Appleton-
to respond to acute stress has two well-defined com- Century-Crofts, Publishing Division of Prentice-Hall, Inc.,
ponents: extensibility, or the ability to resist tension, and Englewood Cliffs, NJ.)
elasticity, or its ability to return to its original shape
when tension is released. As described earlier, collagen
is abundant in the skin, and it is this, which is responsible
for extensibility. Normally, this cross-linked, triple helical lead to a structural instability in elastin, and result in
structure appears relaxed, loose, and convoluted Marfan’s syndrome.
[Fig. 1.14(A)]. But as tension is applied the fibers tend Finally, it is important to understand that collagen and
to take on a more parallel pattern [Fig. 1.14(B)], and a elastin do not exist in a vacuum. This network is lubricated
classic stress – strain curve occurs (Fig. 1.15). This exten- with a mucopolysaccharide rich ground substance, which
sibility has limits as any surgeon who closes soft tissue insulates individual fibers and allows for optimal function.
defects can easily attest. Elastin, on the other hand, gives The dermis is also interspersed with blood vessels, nerves,
skin the ability to snap back after being stretched. Like col- and lymphatics, each of which may be affected by skin
lagen, it is rich in proline, glycine, and hydroxyproline. deformation, and may ultimately, though not necessarily
But, unlike collagen, it has no hydroxylysine, and is not directly, affect the flexibility of skin. Vascular plexes
glycosylated. Its a-helical segments are cross-linked may be obstructed by deformational forces, and lead to
through covalent bonds and coated with a sheath of glyco- congestion, ischemia, necrosis, and ultimately tissue loss
proteins known as fibrillin. Elastin is not distinct from col- and/or scarring. Nerves can be stretched and cause pain
lagen, but instead forms a loose network within the and lymphatics can be obstructed causing either acute or
collagen framework. Interestingly, mutations in fibrillin chronic edema.
16 Functional and Aesthetic Reconstruction of Burned Patients

Figure 1.15 Scanning electron microscope (SEM) photograph

of the collagen fibers of relaxed human dermis. (With permission
from Gibson T, Kenedi RM. The structural components of the
dermis. In: Montagna W, Bentley JP, Dobson RL, eds. The
Dermis, 1970. Courtesy of Appleton-Century-Crofts, Publishing
Division of Prentice-Hall, Inc., Englewood Cliffs, NJ.) Figure 1.16 When skin is stretched, many of the fibers
become aligned in a straight manner in the direction of stretch,
thus imposing a limit on extensibility in that direction. (With per-
21. Viscoelasticity mission from Brown IA. Structural and Mechanic Skin. Ph.D.
Thesis, University of Strathclyde, Glasgow, 1971.)
The fact that skin has the ability to stretch is one that pre-
sents itself in everyday life in both acute and chronic
venues. The concept of viscoelasticity deals with the could be stretched to a greater extent if the load were
former, and the two terms are classically applied to applied then relaxed a number of times, thereby better dis-
describe the skin’s immediate response to an applied placing the ground substance and getting that sometime
force. These are creep and stress relaxation, and as you crucial few millimeters of length (Fig. 1.18). Similarly,
will see, they are basically a way of describing a single “immediate tissue expansion” proponents (38), have
phenomenon from two different points of view. With observed that increased tissue length can be obtained
creep, we observe that skin tends to extend when a con- with load cycling, but that little true increase in skin
stant force is applied over time. Stress relaxation is the length actually occurs. This though, is not the case with
observation that when the skin is stretched to a given chronic or true tissue expansion as described in the follow-
length, the force required to hold it there decreases over ing text.
time. Obviously, the strain curves derived from these
experiments are not linear and flatten as the dermis
22. Tissue Expansion
reaches its expandable limits. These limits, as one might
surmise, are related to the ability of the resident collagen The idea that skin can stretch when force is applied over a
and elastin to “give” by unwinding and becoming more long period of time can easily be observed, for instance, in
parallel. Further, it is also dependent on the viscous mol- the obese patient. Even better, an apparent increase in skin
ecules, which surround and cushion the structural com- area seems to occur when this obese patient loses signifi-
ponents, to “move out of the way” as the skin stretches cant weight and an empty hanging pannus results. The
and thins, namely, the aforementioned mucopolysaccaride question arises, is this increase in area a result of actual
rich, ground substance. skin growth, or simply the realigning of collagen,
Clinically, these phenomena are vitally important, elastin, and ground substance with a measure of dermal
especially when one endeavors to plan the orientation of tearing that occurs with “stretch marks”? Though in the
an incision (Fig. 1.16), or recruit adjacent tissue to close patient described earlier, it is probably a combination of
soft tissue defects with local flaps like Z-plasties both of these, it has been clearly shown that chronic
(Fig. 1.17). In the 1970s, Gibson and Kendi presented force applied to skin can make it grow, and that this
the concept of “load cycling,” pointing out that skin growth can be clinically advantageous when a need to
Properties of the Skin 17

Figure 1.17 Langer lines on the leg. When the skin on the Figure 1.18 Z-plasty technique. (With permission from
front of the thigh was cut along the cleavage lines, most of McCarthy JG. Introduction to plastic surgery. In: McCarthy JG,
the fibers on the cut edge could be seen running parallel to the ed. Plastic Surgery. Vol. 1. General Principles. Philadelphia:
lines. When it was incised at right angles to the lines, most of the W.B. Saunders Co., 1990:1– 68.)
fibers had been cut transversely or obliquely. (With permission
from Gibson T. Physical properties of skin. In: McCarthy JG,
ed. Plastic Surgery. Vol. 1. General Principles. Philadelphia:
W.B. Saunders Co., 1990:207 – 220).
changes to tissue-expanded skin that make this procedure
possible.
In the epidermis, a quantitative increase in thickness
resurface large areas of the body arises (Fig. 1.19). Further, occurs over the typical expansion period of 6– 12 weeks.
experimentation has made it clear that this force can be This is the result of division of the resident keratinocytes.
applied, with the placement of silicone rubber expanders Histologically, the increase in thickness is in the stratum
under normal skin, adjacent to the area to be resurfaced. spinosum, and notably, a significant flattening of the rete
This balloon can then be sequentially filled, initiating the pegs occurs. These changes have been shown to regress
growth of normal skin, ultimately allowing the excision over the next several years. Dermal changes tend to
of the abnormal or scarred tissue and advancement of occur most prominently in the reticular portion, and
normal skin over the area. include an overall thinning which persists for several
Though Dr. Charles Neumann has been credited with years following expansion, a thickening of the collagen
first the use of a latex balloon to expand the skin in a ear bundles with a predictable more parallel arrangement,
reconstruction in 1956, the major developments and scien- and fragmentation of the elastin which tends not to
tific investigation came some 20 years later with the work present as striae. The number and distribution of resident
of Dr. Chedomir Radovan and Dr. Eric Austad in the cells like fibroblasts, mast cells, and macrophages do not
1970s. Radovan (personal communication) developed appreciably change, though presumably the activity of
the closed system silicone balloon expander, and Austad the fibroblasts is altered during the expansion phase. The
(39) was credited with the development of an osmotically dermal appendages like hair follicles, sebaceous and
driven, self-inflating expander. Along with these two inno- eccrine glands do not increase in number and have been
vators, Dr. Gordon Sasaki and Dr. Argenta can also be shown to atrophy, depending on the aggressiveness of
credited with early work leading to the widespread use the expansion. Though tissue expansion has been used
of this technology in the reconstructive arena (Fig. 1.20). with great effectiveness in addressing scalp alopecia as
The clinical details of tissue expansion are discussed else- with type I and some type IIs as in the scale proposed by
where in this text, but it is important to note the physical McCauley (39a), the failure of the hair follicles to
18 Functional and Aesthetic Reconstruction of Burned Patients

TGFb, FGF, PDGF, which act to allow for hemostasis,

and chemotaxis. As the inflammatory phase gives way to
the proliferative phase, these and other growth factors
stimulate keratinocytes and fibroblasts to divide and
migrate into the wound leading to angiogenesis, epithelia-
lization, contraction, and collagen production. In the remo-
deling phase, as the name suggests, components of the
healing wound like fibronectin, proteoglycans, and col-
lagen are converted from a disorganized array to a stable
healed wound or scar through interactions with matrix
metalloproteinase (MMPs) (42) and tissue inhibitor metal-
loproteinase (TIMPs) (43).
The final outcome of this process, the scar or cicatrix, is
defined in medical dictionaries as a mark left over after
the healing of a wound. Interestingly, this phenomenon
does not occur in early fetal life (44,45), but begins at
about the fifth month of gestation. The fact that it exists
after this point suggests that it provides a survival
advantage, and although even at its strongest, it only pro-
vides 80% of the strength of normal skin, scarring
allows us to heal wounds quickly, thereby allowing us to
re-establish a protective, occlusive, and sturdy barrier
(46). Just as wounds heal by epithelization and contrac-
tion, once closed, the resulting scar goes through phases
of maturation.
As can be observed in many clinical scenarios, scarring
Figure 1.19 Burn child undergoing scalp expansion for cover- begins with an immature phase (Fig. 1.21). Commonly
age of burn alopecia. (Courtesy R. L. McCauley, MD, Shriners these scars are red and raised. As the scar matures, it
Hospitals for Children, Galveston, TX.) softens, flattens, and takes on a color closer to the sur-
rounding skin. The length of time that this takes is vari-
able, but most authorities agree that scars mature over a
divide, explains its limited usefulness in large and/or 1- to 2-year period.
patchy hair loss as with some type II and type III alopecia. A number of attempts to classify this progression have
With large losses, the hair becomes noticeably thinner been made, most notably the Vancouver Scar Scale. It
with an increased interfollicular distance. Vascularity has relies on a subjective rating, where an observer assigns
been shown to transiently increase, and the neural points based on the size, shape, texture, and pliability of
network shows few changes with expansion. the scar over time. The reliability and validity of such a
Finally, over the past decade, extensive work has been system have been questioned and attempts to create a
paid to the issue of tissue expansion and the use of more objective evaluation continue (47,48).
postoperative radiation in patients with breast cancer. A Scar maturation may be altered by aging, genetic
significantly higher rate of complications like capsular predisposition, or environmental circumstances, and can
contracture and implant exposure, have been identified, also result in abnormal outcomes like keloid, hypertrophic
and tissue expansion, if not contraindicated, has classically (49), widened, atrophic, or contracted scars. The mechan-
been discouraged (40,41). The histological explanations isms of both normal and abnormal wound healing, as well
have revolved around the irreversible dermal injury, as the best way to treat scarring as a phenomenon, is under
which occurs with subsequent fibrosis, though the histo- intense investigation.
logical explanation has remained unexplained. Hypertrophic and keloid scars represent good examples
of abnormal scarring. Hypertrophic scars tend to remain
within the boundaries of the original injury, and often
23. Scar
begin to regress spontaneously after about a year post-
Normally, after skin is injured, it goes through a series of injury. They are red, raised, inflamed, and often display
phases, namely the inflammatory, proliferative, and remo- symptoms of itching and pain. They are often located
deling. Early in the inflammatory phase, platelets and leu- around joints after burn injury and can lead to scar con-
kocytes release a host of inflammatory mediators like tractures. A cytokine based etiology for this condition
Properties of the Skin 19

Figure 1.20 The 5th National Tissue Expansion Symposium, under the auspices of the Plastic Surgery Educational Foundation, was
held at the Century Plaza Hotel in Century City, CA, in 1989. Left to right: Drs. Ernest Manders, Armand Versaci, Alan Gold, Hilton
Becker, the author, Jacic Fisher, Eric Austad, and John Gibney. (With permission from Sasaki GH. History and evolution of tissue expan-
sion. In: Tissue Expansion in Reconstructive and Aesthetic Surgery. Mosby, 1998:2 –7.)

has been suggested by in vivo experiments showing altera- same as is exemplified by the need for scar releases so
tions in the type I:III collagen ratios, elevated serum often required around the contracted joints of the burn
TGFb1 levels, as well as in vitro experiments showing patient.
alterations in MMP/TIMP ratios (50,51). Keloids may
also be inflamed raised areas displaying similar itchy, 25. Photodamage
painful symptoms, but they differ in that they extend
beyond the boundaries of the original injury and do not Classically, the UV-B wavelengths (290 –320 nm) have
regress. Though no etiology has been clearly elucidated, been blamed for the majority of the injury (54,55), but
more recent work has also implicated UV-A (320 –
alterations in keloid fibroblast TGFb1 sensitivity (52),
400 nm) (56,57). The term solar elastosis has been used
and alterations in cytokines like IL-6 have been shown
in vitro (53). Ultimately, both lead to an abnormal abun- to describe this thickened, nodular, darkened skin. The
dance of collagen, resulting in skin with thickened, inelas- changes include a thickening of the epidermis with
tic properties. increased atypia and loss of keratinocyte polarity, an
increased density of melanocytes, and thickening/hyper-
plasia of the elastic fibers. This accumulation of elastin
24. Special Cases
along with collagens I and III, microfibullar proteins,
There are multiple factors that can affect the properties of and fibronectin eventually degrades leaving a basophilic,
“normal” skin. These may include extrinsic factors like amorphous layer in the papillary dermis (58). Interest-
sun exposure along with intrinsic factors like aging. ingly, and unlike elastin, collagen production is decreased
Though these processes occur simultaneously in any one in sun-damaged skin. Specifically, types I and III, the pre-
individual, they are not the same. The dark, thickened, dominant form in skin, are decreased from 20% to 30% in
leathery, skin on the face of the aging sun worshiper is the papillary dermis (59). Collagen cross-linking has been
very different from the lighter less wrinkled skin on the shown to be decreased (60), and there is an increase in
bathing suite covered areas. Further, scarred skin appears metaloprotease activity (61 – 63). Finally, chronic inflam-
very different from normal skin whether it is “normal,” mation (64) occurs, and all of these together lead to a
hypertrophied, or keloid. Neither does it function the total loss of visoelastic flexibility of the skin.
20 Functional and Aesthetic Reconstruction of Burned Patients

Figure 1.22 The lines of minimal tension of the face and neck.
(With permission from McCarthy JG. Introduction to plastic
surgery. In: McCarthy JG, ed. Plastic Surgery. Vol. 1. General
Principles. Philadelphia: W.B. Saunders Co., 1990:1 – 68.)

Figure 1.21 A young child with untreated immature burns

with neck contractures and immature hypertrophic scars.
(Courtesy of R. L. McCauley, Shriners Hospitals for Children, an increased risk of shearing and overall skin fragility
Galveston, TX.) develops. There is a 6– 8% decrease in the number of
melanocytes in each decade after 30 (67), leading to the
mottling alluded to earlier, and Gilchrest also showed a
decrease in the number of Langerhans cells in aged skin
26. Intrinsic Aging
affecting the immune response.
Any intern who has been called to the bedside of an elderly Notable dermal changes also occur. There is a decrease
patient and asked to place an IV, has personal experience in total density, collagen content, ground substance, and
with the clinical changes that occur in the skin as we age vascularity. The overall number of fibroblasts decreases
(Fig. 1.22). It usually appears thin with a mottled appear- and the elastin degrades over time leading to the thinning,
ance. It is loose and has poor elasticity. It often feels dry laxity, and fine wrinkling characterizing aged skin (22).
with a decreased hair density, and once injured, it takes Further, fibroblasts have a limited ability to divide (50 –
longer to heal than young skin. These phenomena are 100 population doublings in culture). This correlates to
explained by the significant alterations in both the epider- their activity in vivo and as skin ages, fibroblasts become
mis and the dermis. senescent and their ability to respond to injury decreases.
Thinning of the epidermis has been described, but is Their synthetic capacity decreases, and thus, there is a
more related to a flattening of the rete pegs. For the most decreased ability to respond to injury with procollagen
part there is little alteration in the stratum corneum, production (68). They overexpress collagenases (69), and
spinus, or granular layers. The basal layer is altered in underexpress TIMPs (70). Ground substance molecules
that there is a loss of the convoluted interface between like dermatan sulfate and hyaluronic acid also decrease
the epidermis and dermis caused by a decrease in microvil- leading to a loss of hydration. The number of skin appen-
lar projections between the epidermal basal cells and the dages changes with a loss of eccrine sweat glands, but
dermis (65). This flattening leads to an overall decrease there is an increase in the size and number of sebaceous
in the shared dermal – epidermal surface area (66), and glands (although there is a decrease in their activity).
with the decrease in the villous cytoplasmic projections, Finally, hair follicles decrease in number, size, and activity
which help to sustain the dermal –epidermal adherence, leading to fewer, thinner less pigmented hairs.
Properties of the Skin 21

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strains of hairless mice. Cancer Res 1977; 37:3243–3248. Exp Cell Res 1992; 201:373 – 379.
2
Wound Healing

MICHAEL K. OBENG, LINDA G. PHILLIPS

University of Texas Medical Branch, Galveston, Texas, USA

I. Introduction 23 B. Proliferative Phase 31

II. Pathophysiology of the Burn Wound 23 1. Angiogenesis 32
2. Fibroplasia 33
III. Reparative Process of Wounds 25
C. Maturational and Remodeling Phase 33
A. Inflammatory Phase 26
D. Factors Affecting Wound
1. Hemostasis 27
Healing 35
2. Inflammation 27
1. Drugs 38
3. Leukocytes 29
4. Macrophage 30 Acknowledgments 38
5. Lymphocytes 31 References 38
6. Cytokines 31

I. INTRODUCTION II. PATHOPHYSIOLOGY OF THE

BURN WOUND
Plastic and reconstructive surgeons are expected to heal
wounds with minimal or no scarring. However, burn Functional and cosmetic outcomes of the reconstructed
wounds and wounds that are created in burned areas of burned skin depend in large part on how the initial burn
the skin possess a heightened challenge to even the most wounds are managed. The acute burn wound that heals
astute reconstructive surgeon. The ultimate goal is to get in ,2 weeks presents with minimal scarring, possibly
these specialized wounds to heal in a timely fashion with eliminating future reconstructive efforts.
very little scarring, good cosmesis, and most importantly The acute burn wound causes both local and systemic
excellent functional outcome. To achieve these goals, we effects mediated by host responses that can sometimes
need to understand how these wounds heal and what we be very devastating. Early excision and grafting of burn
can do to optimize this process. In this modern era of mol- wounds can eliminate some of the systemic response and
ecular biologic technique, these wounds can be mani- improve healing. The burn wound can be divided into
pulated to some extent with good clinical outcome. The three zones based on histological findings as proposed
last two decades have witnessed more advances in the by Jackson (4) in the early 1950s (Fig. 2.1).
art of wound care than what was available 100 years ago The part of the skin where the initial contact is made is
(1 – 3). The goals of this chapter are to briefly describe known as the zone of coagulation (necrosis). This zone is
the pathophysiology of the burn wound, the reparative characterized by tissue destruction and necrosis usually
process of the wound, factors affecting wound healing, starting at the point of contact in the epidermis and extend-
and cytokine manipulation of the wound. ing downward into the dermis. This is created as a result of

23
24 Functional and Aesthetic Reconstruction of Burned Patients

Figure 2.1 Diagrammatic rendition of Jackson’s three zones of burn injury. Superficial 28 injury on left, deeper 28 injury on right.
(In deep 28 burn note potential for conversion to full-thickness tissue loss if zone of stasis progresses to necrosis.) (With permission
from Williams WG. Pathophysiology of the burn wound. In: Herndon DN, ed. Total Burn Care. 2nd ed. Philadelphia: W.B. Saunders
Company, 2002:514 – 521.)

denaturing of proteins beyond repair caused by the high space. Sometimes this can be overwhelming, leading to
thermal energy (5). Protein denaturation with subsequent hypovolemic shock. Cellular recovery in this zone can
tissue necrosis depends mainly on the temperature to proceed to total recovery.
which tissues are exposed and the duration of contact. Edema in burn wounds can be more pronounced in
This phenomenon has been well proven by Moritz and comparison to other wounds. This produces harmful
Henriquez (5) in their classical paper in 1947. effects on nutrient and oxygen delivery, as well as
Surrounding the zone of coagulation peripherally and causing significant decreases in intravascular volume
extending into the dermis is the zone of stasis (ischemia). (13 – 15). In addition, large quantities of protein leak
This is the zone of lesser injury. Initially the cells are through the burn-induced endothelial cell gap (16,17).
viable, but can progress clinically to skin necrosis. This Chemical mediators such as histamine, bradykinin,
occurs because the circulation in this zone is significantly sensory neuropeptides, and oxygen-free radicals can
impaired (6). The decreased circulation results from events cause some of the increases in vascular permeability due
in the microvasculature in a well-concerted effort, orche- to their own vasodilatory effects (17 – 19). Prostanoids
strated by platelets and its derived factors leading to found in burn fluid may also account for some of the
vasoconstriction (7). In addition, thermally injured eryth- edema formation. Some studies have demonstrated that
rocytes lose their ability to conform to the microvessels, the inhibitors of prostaglandin production such as ibupro-
with concomitant reduction in oxygen delivery (8). fen and indomethacin can be of use with some success to
Blood flow impairment continues for up to 24 h with ces- reduce edema formation (20 – 23). Other causes of edema
sation in about 48 h after sustaining the burn injury (9). It include elevated capillary filtration pressures from
is believed that under favorable conditions, stasis and impaired outflow in the venous system, secondary to slud-
ischemia may be reversed with cell recovery within a ging and agglutination of erythrocytes in the postcapillary
week (9). The cells in this zone are very susceptible to venules (24). Serotonin mediated venular constriction also
further insult during recovery (10). Infection, changes in serve to elevate capillary filtration pressure and sub-
pressure as in hypovolemia and overresuscitation, and sequent increased edema. Hydrostatic pressure reduction
even electrolyte abnormalities such as hypernatremia can occurs in the interstitium in the early postburn period
cause further necrosis during the recovery phase (10). (25). There continues to be efflux of intravascular fluid,
Robson and others have extensively studied the pathophy- since the interstitial pressures are too low to counteract
siology of this zone, and the ischemic effects of prosta- this effect. The time course for edema formation is very
glandin F2a and thromboxane A2 (6,8,11,12). Specific important. The formation of edema is rapid, occurring
thromboxane inhibitors and more generalized inhibitors within the first 3 h after injury. A biphasic pattern explains
of prostanoids have been used experimentally with some this phenomenon with a transient phase lasting 15 min
success in improving dermal perfusion after thermal followed by a sustained phase. The edema is maximized
injury (9,11,12). within 24 h postinjury and can persist for up to 3 days.
The zone of hyperemia surrounds the zone of stasis. The severity of the burn injury determines the extent to
There is increased vascular permeability secondary to pro- which and how rapidly the edema forms. Subsequently,
nounced vasodilation. Edema ensues from extravasation the edema resolves, but slowly, depending on the physio-
of fluid from the intravascular space to the interstitial logic condition of the wound and overall health status of
Wound Healing 25

Healing Responses
Hemostasis 1. Stop Bleeding
Inflammation 2. Chemotaxis Inflammatory (Reactive)

3. Epithelial Migration
Connective Tissue
4. Proliferation Proliferative (Regenerative)
Regeneration
5. Maturation

3. Contraction
Maturational (Remodeling)
Contracture 4. Scarring
5. Remodeling of Scar

Figure 2.2 Schematic of wound healing continuum. [With permission from Phillips (26).]

the patient. The pathophysiology of the burn wound con- fashion, unless interrupted. This cascade involves soluble
tinues to be uncovered leading to better management of mediators, different cell types and elements, and the extra-
the acute phase of burn injury. It is only when this cellular matrix (ECM). The healing cascade for wounds
process is maximally controlled that early wound closure differs among different tissue types. In this discussion,
is possible. Subsequently, our reconstructive efforts may we will focus on the broad spectrum of the wound
be more fruitful, yielding better cosmesis and function. healing process. This cascade involves three main
phases: inflammatory (coagulation and inflammation),
proliferative (cell proliferation and matrix repair), and
III. REPARATIVE PROCESS OF WOUNDS remodeling of the scar tissue. These phases are a conti-
nuum and overlap, and can last up to several months
Wound healing is a complex, dynamic, and interactive (Fig. 2.2). For simplicity and clarity purposes, the phases
process that progresses in an orderly and predictable of wound healing will be described in a linear fashion.

Figure 2.3 The immediate response to injury forms a fibrin mesh clot with platelets that release coagulation factors and cytokines,
initiating healing. [With permission from Phillips (26).]
26 Functional and Aesthetic Reconstruction of Burned Patients

A. Inflammatory Phase achieved. Clot, a conglomerate of fibrin mesh, aggregated

platelets, and blood cells, signals the end of the hemostatic
The inflammatory phase of wound healing is the immediate stage (Fig. 2.3) (28). The principal cell type during this
response to the injury characterized and heralded by hemos- phase is the platelet. The events leading to hemostasis
tasis and inflammation. John Hunter first described the include platelet aggregation, vasoconstriction, and depo-
characteristics of inflammation in 1794 (27). The four sition of fibrin from the clotting cascade (Fig. 2.4). Platelets
characteristics of inflammation are erythema (rubor), initiate this phase of wound healing after the injury by releas-
edema (tumor), heat (calor), and pain (dolor). The wound ing a number of soluble factors, including platelet derived
healing process cannot continue, until hemostasis is growth factor (PDGF), insulin-like growth factor-1

Figure 2.4 Diagrams of interactions among coagulation factors. (A) The intrinsic, extrinsic, and common pathways in their simplest
forms. (B) Critical stages in activation and control of blood coagulation. (C) This diagram is organized around the contact surface and
the phospholipids surface. Solid lines with arrows indicate proteolytic activation. Broken lines with arrows indicate proteolytic inactivation.
Solid lines with bars indicate complex formation and inactivation. The stippled patches indicate binding of proteins to surfaces or to one
another. The subscript a indicates proteins that are zymogens and can be converted to active enzymes. PK ¼ prekallikrein; HMWK ¼ high
molecular weight kininogen; TF ¼ tissue factors; PI ¼ alpha2-antiplasmin; TM ¼ thrombommodulin; EPI ¼ extrinsic pathway inhibitor;
ATIII ¼ antithrombin III; HCII ¼ heparin cofactor II. (With permission from Mosher DF. Disorders of blood coagulation. In: Wyngaarden
JB, Smith LH Jr, Bennett JC, eds. Cecil Textbook of Medicine. 19th ed. Philadelphia: W.B. Saunders Company, 1992:999–1017.)
Wound Healing 27

(IGF-1), epidermal growth factor (EGF), fibroblast growth derived from complex interactions result in the production
factor (FGF), and transforming growth factor-b (TGF-b). of thrombin that serves as a catalyst for the formation of
fibrin from fibrinogen (Fig. 2.4).
In addition to converting fibrinogen to fibrin, thrombin
1. Hemostasis also stimulates increased vascular permeability and aids in
The hemostatic stage is the cornerstone of the inflam- the extravascular migration of inflammatory cells (34).
matory phase. Tissue injury causes damage to blood The fibrin strands ensnare red cells, aggregated platelets,
and other harmless debris to form a clot (28). The
vessels, disrupting the lining of the vessels. Platelets
formed clot seals the wound preventing contamination
bind to the exposed collagen types IV and V in the suben-
from the outside environment as well as fluid and electro-
dothelium and become activated in the process (26,29).
The activated platelets in turn release a host of biologically lyte losses. The lattice meshwork formed by fibrin and the
active soluble factors from storage organelles: alpha gran- trapped cells, becomes the scaffold for the key players of
ules, dense bodies, and lysosomes within their cytoplasm the wound-healing cascade. Vitronectin, derived from
(Table 2.1) (30 –32). The contents of the alpha granules the alpha granules of platelets and serum, coats fibrin.
are mainly immunoregulatory and procoagulation factors This interaction produces “glue-like” material that binds
fibronectins, produced by fibroblast and epithelial cells
and participate in the early as well as the late phase of
(35). The fibrin– vitronectin – fibronectin complex is also
wound healing. The contents of the dense bodies are
an important matrix framework, with over a dozen
mainly energy providing factors, while that of the lyso-
somes are degradative enzymes. PDGF, TGF-b and binding sites on the fibronectin molecule for cellular
FGF-2 are some of the most important factors. attachments and migration along the matrix (27). This
As the subendothelium is exposed and the platelets matrix selectively traps circulating cytokines for use in
become activated, both the intrinsic and the extrinsic path- the later stages of the cascade (36). Any process that inter-
ways of the clotting cascade are initiated. While the extrin- feres with fibrin formation disrupts the matrix scaffold and
ultimately impairs wound healing (37 –39).
sic cascade is essential for normal wound healing, the
intrinsic cascade is not required (33). The extrinsic
pathway is initiated by exposure of blood and platelets 2. Inflammation
to a factor in the subendothelium named “tissue factor”
that binds factor VIII activating it to f-VIIIa. Factor XII The arachidonic acid cascade (Fig. 2.5) also plays a sig-
activates the intrinsic pathway after exposure of blood nificant role in the inflammatory phase. Thromboxane A2
and platelets to the subendothelial layer. Activated (TXA2) and prostaglandin (PG) F-2a (PGF-2a) aid in
factors VII and XII, orchestrated by soluble factors platelet aggregation and vasoconstriction (26). While the
role of the products of the arachidonic acid cascade is to
regulate the amount of injury, localized ischemia can
ensue causing further damage to cell membranes and elab-
Table 2.1 Released Factors from Platelets Storage Granules
oration of the cascade with more release of PGF-2a and
TXA2.
I. Alpha 1 granules II. Dense bodies The inflammation stage is characterized by increased
1. Platelet-derived growth 1. Vasoactive amines vascular permeability and leukocyte migration mediated
factor (PDGF) (serotonin) by chemoattractants into the extravascular space (26).
2. Transforming growth factor-b 2. Calcium The purpose is to deliver inflammatory cells to the
(TGF-b) 3. ADP
injured site to kill bacteria and eliminate debris. These
3. Insulin-like growth 4. ATP
inflammatory cells include leukocytes, lymphocytes, and
factor-1 (IGF-1)
4. Fibronectin III. Lysosomes macrophages.
5. Fibrinogen 1. Hydrolase The signs of inflammation are evident shortly after the
6. Thrombospondin 2. Protease initial vasoconstrictive episode which reverses in 15 min
7. Von Willebrand’s (29). Vasodilatation occurs causing erythema and heat.
factor (vWF) The edema formation that follows, in large part, contrib-
8. Albumin utes to the sensation of tightness and pain. This edema for-
9. IgG mation is a result of gaps developing in the endothelial
10. Coagulation factors V and VIII cells lining the capillaries in the area of insult with conco-
11. Fibroblast growth factor-2 (FGF-2) mitant leakage of plasma and other factor into the extra-
12. Platelet-derived epidermal growth
vascular space (17). The vasodilitory effect seen is
factor (EGFs)
mediated by a host of factors derived from plasma endo-
13. Endothelial cell growth factors
thelial products and mast cells (40 – 42). These factors
28 Functional and Aesthetic Reconstruction of Burned Patients

Figure 2.5 (A) Metabolism of arachidonic acid by cyclo-oxygenase. The major tissues of origin of the eicosanoids. (B) Metabolism
of arachidonic acid by lipoxygenase enzymes. (With permission from FitzGerald GA. Prostaglandins and related compounds.
In: Wyngaarden JB, Smith LH Jr, Bennett JC, eds. Cecil Textbook of Medicine. 19th ed. Philadelphia: W.B. Saunders Company,
1992:1206 – 1212.)
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