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PROCEDURES IN COSMETIC DERMATOLOGY SERIES:

CHEMICAL PEELS, THIRD EDITION ISBN: 978-0-323-65389-3
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 CONTRIBUTORS

Richard Hector Bensimon, MD Joe Niamtu III, DMD

Medical Director Private Practice
Plastic Surgery Cosmetic Facial Surgery
Bensimon Center, Richmond, VA, USA
Portland, OR, USA
Suzan Obagi, MD
Claudia Borelli, MD Associate Professor of Dermatology,
Associate Professor of Dermatology Associate Professor of Plastic Surgery,
Director, Aesthetic Dermatology and Laser Unit Director
­Department of Dermatology Eberhard-Karls-­ UPMC Cosmetic Surgery & Skin Health Center,
University Tuebingen Sewickley, PA, USA
President of German Aesthetic Dermatology and
Cosmetology Working group ADK Past President Jeave Reserva, MD
International Peeling Society IPS Dermatology Resident
Tuebingen, Germany Division of Dermatology
Loyola University Medical Center,
Desmer Destang, DDS, MSc (Ortho), MSc (Derm), Maywood, IL, USA
MSc (Aesth Med)
Medical Director, Dermalogics Aesthetic Dermatology, Barry Resnik, MD
St. Lucia Private Practice
Lecturer in Cosmetic Medicine, University of South Resnik Skin Institute Miami
Wales, Cardiff, UK Voluntary Clinical Professor
Dr Phillip Frost Department of Dermatology and
Luc Dewandre, MD ­Cutaneous Surgery
Consultant, Internal Medical Service, Paris, France University of Miami Miller School of Medicine,
Consultant in Aesthetic Medicine, Vitality Institute, Miami, FL, USA
Miami, FL, USA
Peter Rullan, MD
Sabrina Fischer, MD Medical Director
Associate Professor of Dermatology Dermatology Institute
Aesthetic Dermatology and Laser Unit Department of Volunteer Clinical Faculty
Dermatology Eberhard-Karls-University University of California San Diego,
Tuebingen San Diego, CA, USA
Tuebingen, Germany
Jaishree Sharad, MBBS, DDV, MD
Marina Landau, MD Cosmetic Dermatologist
Senior Dermatologist Medical Director
Dermatology Skinfiniti Aesthetic Skin and Laser Clinic,
Wolfson Medical Center, Mumbai, India
Holon, Israel

iii
iv CONTRIBUTORS

David Surprenant, MD Rebecca Tung, MD

Dermatology Resident Mohs and Dermatologic Surgeon
Division of Dermatology Florida Dermatology and Skin Cancer Centers,
Loyola University Medical Center, Winter Haven, FL, USA
Maywood, IL, USA
Carlos G. Wambier, MD, PhD
Alain Tenenbaum, MD, PhD, DSc Assistant Professor of Dermatology, Clinician Educator
Swiss National Delegate Department of Dermatology, The Warren Alpert Medical
EAFPS, School of Brown University
Lübeck, Germany, President Providence, RI, USA
SACDAM,
Engelberg, Switzerland, Vice President Carolyn Willis, MD
IPSC, Dermatology
Alpnach Dorf, Switzerland, Researcher University of Pittsburgh Medical Center,
Research and Development Sewickley, PA, USA
Styling Cosmetics AG,
Engelberg, Switzerland

Yardy Tse, MD
Assistant Clinical Professor,
Department of Medicine/Dermatology,
University of California, San Diego; SkinCare
Physicians and Surgeons Inc., Encinitas, CA, USA
 S E R I E S P R E FAC E , F I R S T E D I T I O N
While dermatologists have been procedurally inclined what it is not. It is not a comprehensive text grounded
since the beginning of the specialty, particularly rapid in theoretical underpinnings. It is not exhaustively ref-
change has occurred in the past quarter century. The erenced. It is not designed to be a completely unbiased
advent of frozen section technique and the golden age review of the world’s literature on the subject. At the
of Mohs skin cancer surgery has led to the formal incor- same time, it is not an overview of cosmetic procedures
poration of surgery within the dermatology curriculum. that describes these in generalities without providing
More recently, technological breakthroughs in mini- enough specific information to actually permit someone
mally invasive procedural dermatology have offered an to perform the procedures. And importantly, it is not so
aging population new options for improving the appear- heavy that it can serve as a doorstop or shelf filler.
ance of damaged skin. What this book and this series offer is a step-by-
Procedures for rejuvenating the skin and adjacent step, practical guide to performing cutaneous surgical
regions are actively sought by our patients. Significantly, procedures. Each volume in the series has been edited
dermatologists have pioneered devices, technologies, and by a known authority in that subfield. Each editor has
medications that have continued to evolve at a startling recruited other equally practical-minded, technically
pace. Numerous major advances, including virtually all skilled, hands-on clinicians to write the constituent
cutaneous lasers and light-source based procedures, botu- chapters. Most chapters have two authors to ensure that
linum exotoxin, soft tissue augmentation, dilute anesthesia different approaches and a broad range of opinions are
liposuction, leg vein treatments, chemical peels, and hair incorporated. On the other hand, the two authors and
transplants, have been invented or developed and enhanced the editors also collectively provide a consistency of tone.
by dermatologists. Dermatologists understand procedures, A uniform template has been used within each chapter
and we have special insight into the structure, function, and so that the reader will be easily able to navigate all the
workings of skin. Cosmetic dermatologists have made reju- books in the series. Within every chapter the authors
venation accessible to risk-averse patients by emphasizing succinctly tell it like they do it. The emphasis is on thera-
safety and reducing operative trauma. No specialty is better peutic technique; treatment methods are discussed with
positioned than dermatology to lead the field of cutaneous an eye to appropriate indications, adverse events, and
surgery while meeting patient needs. unusual cases. Finally, this book is short and can be read
As dermatology grows as a specialty, an ever-increas- in its entirety on a long plane ride. We believe that brev-
ing proportion of dermatologists will become proficient ity paradoxically results in greater information transfer
in the delivery of different procedures. Not all dermatol- because cover-to-cover mastery is practicable.
ogists will perform all procedures, and some will perform Most of the books in the series are accompanied by
very few, but even the less procedurally directed among videos that demonstrate the procedures discussed in that
us must be well-versed in the details to be able to guide text. Some of you will turn immediately to the video and
and educate our patients. Whether you are a skilled der- use the text as a backup to clarify complex points, whereas
matologic surgeon interested in further expanding your others will prefer to read first and then view the video to
surgical repertoire, a complete surgical novice wish- see the steps in action. Choose what suits you best.
ing to learn a few simple procedures, or somewhere in We hope you enjoy this book and the rest of the
between, this book and this series are for you. books in the series and that you benefit from the many
The volume you are holding is one of a series enti- hours of clinical wisdom that have been distilled to pro-
tled Procedures in Cosmetic Dermatology. The purpose duce it. Please keep it nearby where you can reach for it
of each book is to serve as a practical primer on a major when you need it.
topic area in procedural dermatology. Jeffrey S. Dover, MD, FRCPC,
If you want to make sure you find the right book for Murad Alam, MD, MSCI
your needs, you may wish to know what this book is and

v
S E R I E S P R E FA C E , T H I R D E D I T I O N
As this Procedures in Cosmetic Dermatology series chapter-by-chapter in various electronic formats and
undergoes another iteration, it is clear our mission on several platforms. We have expanded the video
that was initiated 15 years ago to provide succinct and offerings because they are worth many pages of text
current expert guidance regarding particular cosmetic and are easier to follow.
procedures remains highly relevant. Our portable, travel- As always, we are very grateful to our chapter book
ready format continues to match the ever-shortening editors and authors. These practitioners are among
attention span of the overwhelmed physician. Indeed, the most prominent, bright, erudite, and skilled in the
similar series of slim volumes have emerged in this and world. They have worked tirelessly to provide a uniform
other procedural specialties—versions of the sincerest tone and structure. It is our hope that you find that these
form of flattery. multiauthored books read like a single person wrote
Even so, changes need to be made. As the evolution them, whose writing is a paragon of clarity.
and exponential growth of cosmetic dermatology con- Our thanks are also due to Elsevier, our publisher
tinues, new procedures are created, and multiple vari- since the start. Elsevier has provided our rapid publish-
ants of existing drugs, devices, and techniques emerge. ing window, which allows content to be put out and dis-
The volumes in the series have been updated to reflect seminated before it goes out of date.
these advances so that the books are now better but Finally, thanks to you, the reader, for continuing to
remain concise and highly practical. use these texts. We wish you the joy of learning some-
We are also cognizant of the decline of paper pub- thing new and then delighting your patients with your
lishing. To preserve the environment and provide freshly honed skills.
content everywhere, all the time, and on all types Jeffrey S. Dover, MD, FRCPC
of media, the series will be available in whole and Murad Alam, MD, MSCI

vi
 CHEMICAL PEELS, THIRD EDITION
It is with much excitement that I bring to you the third ethnically diverse population, we need a tool such as
edition of Chemical Peels! This latest textbook on peels chemical peels to allow us to treat every patient with any
will take your knowledge to the next level, building on skin type that comes to us seeking cosmetic enhance-
what was covered in previous editions. Chemical peels ment.
will be covered by experts recognized worldwide for I am truly humbled and grateful to work with col-
their innovation, talent, and skills. This international leagues from all over the world on this edition, and I
group of thought leaders will cover the entire approach thank them for their hard work in bringing to you an
to the skin resurfacing patient from evaluation, to skin exceptional textbook. I want to also recognize and
preparation, to performing peels ranging from light give special thanks to Meghan Andress at Elsevier for
peels to the advanced deep peels, and finally to recog- the patience and guidance she offered all the authors.
nizing and managing complications. The new edition Furthermore, our series editors, Murad Alam, MD, and
features many new chapters dedicated to an in-depth Jeffrey Dover, MD, deserve special recognition for their
dive into a specific peel or skin condition. These new tireless efforts in creating a series of textbooks focused
chapters include trichloroacetic acid (TCA) peels of on cosmetic dermatology procedures and for their guid-
the chest, neck, and upper extremities; peels as an adju- ance when the content of this book was being developed.
vant treatment of acne; chemical peels in male patients; Lastly, to my family, thank you, thank you, thank
several chapters on unique approaches to acne scars; a you! It was a busy year to say the least, but knowing I had
chapter on combining peels with surgical procedures; your support made it all worthwhile! I survived many
and several chapters that illustrate safely performing weekends and evenings of writing and editing but made
deeper, modified phenol peels with wonderful photo- sure to get to all the important family celebrations and
graphs to accompany the text. Videos of various proce- school achievements. It was worth the effort!
dures will allow easy incorporation of chemical peeling I hope, as you read through this textbook, your inter-
techniques into your practice. est in peels is kindled and your desire to hone your skills
Once again, chemical peels have shown themselves in this field is heightened. I am sure I speak on behalf
to be time-proven methods with unparalleled flexibil- of all my coauthors when I say, once a “peeler” always a
ity in their performance. Chemical peels have resurged “peeler.” Hopefully you will join us as a fellow “peeler”!
in popularity as courses and didactic sessions are once Sincerely,
again being offered to physicians. With a growing, Suzan Obagi, MD

vii
 LIST OF VIDEOS

 ideo 1. Alpha Hydroxy Acid Peel

V Video 8. Phenol Peeling - 4
Video 2. Salicylic Acid Peel Video 9. Blue Peel and Hetter VL Medium-Depth Peel
Video 3. TCA Peel - 1 Video 10. A combination of Microneedling and
Video 4. TCA Peel - 2 Chemical Peels for the Treatment of Acne Scars
Video 5. Phenol Peeling - 1 Video 11. Carbolic CROSS
Video 6. Phenol Peeling - 2 Video 12. Chemical Peel Over Facelift
Video 7. Phenol Peeling - 3 Video 13. A Medium-Depth TCA Peel on Dark Skin

ix
 PART 1 Introductory Chapters

1
The Chemistry of Peels: A
Hypothesis of Mechanism of
Action and Classification of Peels
Luc Dewandre, Alain Tenenbaum, Desmer Destang

A chemical peel is a treatment technique used to improve replacement: destruction, elimination, and regeneration,
and smooth the facial and/or body skin’s texture using a all accompanied by a controlled stage of inflammation.
chemical solution that causes the dead skin to slough off A brief study of the chemistry of the molecules and
and eventually peel off. The regenerated skin is usually solutions used in chemical peels immediately questions
smoother, healthier, and less wrinkled than the old skin. the hypothesis that acidity is the only basis for the action
It is advised to seek training with a specialist such as of peeling solutions. In fact, with the exception of tri-
a dermatologist, plastic surgeon, otorhinolaryngologist chloroacetic acid (TCA) and nonneutralized glycolic
(facial plastic surgeon), or oral-maxillofacial surgeon acid solutions, the most commonly used peeling solu-
who is experienced in the specific types of peels you tions are only weakly acidic, and phenol and resorcinol
wish to perform. mixtures may not be acidic at all, having a pH greater
than 7 in some formulations.
This chapter will discuss the elementary chemistry
INTRODUCTION concepts that, along with a review of the chemistry of
This chapter proposes a classification of chemical peels the skin, should help explain the possible interactions
based on the mechanism of action of chemical peel solu- between different peeling solutions and the skin. Finally,
tions. The traditionally accepted mechanism has been two classifications of solutions for peelings will be pro-
based on the concept that the effect of a peeling solution posed, one according to their mechanisms of action
on the skin is based purely on its acidity. By using elemen- (classification of L. Dewandre) and the other according
tary concepts in chemistry, three separate mechanisms of to chemical parameters (structure of the molecule, pKa,
action for chemical peeling solutions are explained: etc; or classification of A. Tenenbaum).
1. Acidity
2. Toxicity USEFUL ELEMENTS OF BASIC
3. Metabolic interactions
The literature devoted to chemical peels is full of
CHEMISTRY
information about the methodology, indications, con- Understanding some of the basic concepts of chemistry
traindications, side effects, and results obtained. With- is necessary to truly understand chemical peels. Mineral
out any proof, acidity has always been assumed to be the and organic chemistry are taught as biochemistry to
sole mechanism of action of peeling agents. All peeling medical students, but most practicing physicians do not
agents were assumed to induce the three stages of tissue remember these fundamental principles.
1
2 PART 1 Introductory Chapters

Also chemistry has been unfortunately neglected in differently than Arrhenius acids, can also be used to
cosmetic dermatology and aesthetic medicine courses, describe molecular compounds, whereas Arrhenius
masters workshops, and congresses. A brief review of use- acids must be ionic compounds.
ful information should help update most practitioners. In 1923 chemists Johannes Nicolaus Brønsted and
Thomas Martin Lowry independently recognized that
Acids acid–base reactions involve the transfer of a proton. A
An acid (from the Latin acidus, meaning “sour”) is tradi- Brønsted–Lowry acid (or simply Brønsted acid) is a spe-
tionally considered any chemical compound that, when dis- cies that donates a proton to a Brønsted–Lowry base.
solved in water, gives a solution with a hydrogen ion activity Brønsted–Lowry acid–base theory has several advan-
greater than in pure water, i.e., a pH less than 7.0. That tages over Arrhenius theory. Consider the following
approximates the modern definition of Johannes Nicolaus reactions of acetic acid (CH3COOH) (used as a chemical
Brønsted and Martin Lowry, who independently defined an peel for the décolleté by some great peelers like L. Wiest),
acid as a compound that donates a hydrogen ion (H+) to the organic acid that gives vinegar its characteristic taste:
another compound (called a base). Acid–base systems are
O OH2 O _
different from redox reactions in that there is no change in +
C O H C O OH2
oxidation state. Acids can occur in solid, liquid, or gaseous
H3C H3C
form, depending on the temperature. They can exist as pure
H
substances or in solution. Chemicals or substances having
the property of an acid are said to be acidic (adjective).
O NH3 O _ +
Arrhenius Acids C O H C O NH2
H3C H3C
The Arrhenius concept is the easiest one retained by
most peelers, because most peeling acids are ionic com- H
pounds, acting as a source of H3O+ when dissolved in
water. Both theories easily describe the first reaction:
The Swedish chemist Svante Arrhenius attributed the CH3COOH acts as an Arrhenius acid because it acts as
properties of acidity to hydrogen in 1884. An Arrhenius a source of H3O+ when dissolved in water, and it acts
acid is a substance that increases the concentration of as a Brønsted acid by donating a proton to water. In the
the hydronium ion, H3O+, when dissolved in water. This second example CH3COOH undergoes the same trans-
definition stems from the equilibrium dissociation of formation, donating a proton to ammonia (NH3), but it
water into hydronium and hydroxide (OH−) ions: cannot be described using the Arrhenius definition of an
acid because the reaction does not produce hydronium.
H 2O( l )+ H 2O( l ) ⇌ H 3O +(aq)+ OH – (aq)
As with the acetic acid reactions, both definitions
In pure water most molecules exist as H2O, but a small work for the first example, where water is the solvent
number of molecules are constantly dissociating and and a hydronium ion is formed. The next reaction does
reassociating. Pure water is neutral with respect to acid- not involve the formation of ions but can still be viewed
ity or basicity, because the concentration of hydroxide as a proton transfer reaction.
ions is always equal to the concentration of hydronium
ions. An Arrhenius base is a molecule that increases the Lewis Acids
concentration of the hydroxide ion when dissolved in The Brønsted–Lowry definition is the most widely used
water. Note that chemists often write H+(aq) and refer to definition; unless otherwise specified, acid–base reac-
the hydrogen ion when describing acid–base reactions, tions are assumed to involve the transfer of a proton
but the free hydrogen nucleus, a proton, does not exist (H+) from an acid to a base.
alone in water; it exists as the hydronium ion, H3O+. A third concept was proposed by Gilbert N. Lewis
that includes reactions with acid–base characteristics
Brønsted Acids that do not involve a proton transfer. A Lewis acid is a
Although the Arrhenius concept is useful for describ- species that accepts a pair of electrons from another spe-
ing many reactions, it is also quite limited in its scope. cies; in other words, it is an electron pair acceptor. Brøn-
Brønsted acids act by donating a proton to water and, sted acid–base reactions are proton transfer reactions,
 CHAPTER 1 The Chemistry of Peels: A Hypothesis of Mechanism of Action 3

whereas Lewis acid–base reactions are electron pair respectively). Note that the acid can be the charged spe-
transfers. All Brønsted acids are also Lewis acids, but cies and the conjugate base can be neutral, in which
not all Lewis acids are Brønsted acids. Contrast the fol- case the generalized reaction scheme could be written
lowing reactions, which could be described in terms of as HA ⇌ H+ + A. In solution there exists an equilibrium
acid–base chemistry: between the acid and its conjugate base. The equilibrium
constant K is an expression of the equilibrium concen-
F F trations of the molecules or the ions in solution. Brack-
- - ets indicate concentration, such that [H2O] means the
B F F B F concentration of H2O. The acid dissociation constant Ka
F F is generally used in the context of acid–base reactions.
F
The numerical value of Ka is equal to the concentration
of the products divided by the concentration of the reac-
tants, where the reactant is the acid (HA) and the prod-
ucts are the conjugate base and H+.
H
+ + [H +] [A −]
Ka =
N H H N H [HA]
H H The stronger of two acids will have a higher Ka
H H than the weaker acid; the ratio of hydrogen ions
to acid will be higher for the stronger acid because
In the first reaction a fluoride ion, F−, gives up an the stronger acid has a greater tendency to lose its
electron pair to boron trifluoride to form the product proton. Because the range of possible values for Ka
tetrafluoroborate. Fluoride “loses” a pair of valence elec- spans many orders of magnitude, a more manageable
trons because the electrons shared in the B–F bond are constant, pKa, is more frequently used, where pKa
located in the region of space between the two atomic = −log10Ka. Stronger acids have a smaller pKa than
nuclei and are therefore more distant from the fluoride weaker acids. Experimentally determined pKa at 25°C
nucleus than they are in the lone fluoride ion. BF3 is in aqueous solution are often quoted in textbooks and
a Lewis acid because it accepts the electron pair from reference material.
fluoride. This reaction cannot be described in terms of
Brønsted theory, because there is no proton transfer. The
second reaction can be described using either theory. A Acid Strength
proton is transferred from an unspecified Brønsted acid For peelers, the notion of acid strength is very import-
to ammonia, a Brønsted base; alternatively, ammonia ant, because stronger acids have a higher Ka and a lower
acts as a Lewis base and transfers a lone pair of electrons pKa than weaker acids.
to form a bond with a hydrogen ion. The species that For our classification, two parameters have to be
gains the electron pair is the Lewis acid; for example, the taken into consideration for peelers:
oxygen atom in H3O+ gains a pair of electrons when one 1. The pKa, a synonym of the acid’s strength.
of the H–O bonds is broken and the electrons shared 2. The pH, a synonym of the penetration for the selected
in the bond become localized on oxygen. Depending acid.
on the context, Lewis acids may also be described as a For chemists, the strength of an acid refers to its abil-
reducing agent or an electrophile. ity or tendency to lose a proton. A strong acid is one
that completely dissociates in water; in other words, one
Dissociation and Equilibrium mole of a strong acid, HA, dissolves in water, yielding
Reactions of acids are often generalized in the form one mole of H+ and one mole of the conjugate base, A−,
HA ⇌ H+ + A−, where HA represents the acid and A− is and none of the protonated acid HA. In contrast a weak
the conjugate base. Acid–base conjugate pairs differ by acid only partially dissociates, and at equilibrium both
one proton and can be interconverted by the addition the acid and the conjugate base are in solution. In water
or removal of a proton (protonation and deprotonation, each of these essentially ionizes 100%. The stronger an
4 PART 1 Introductory Chapters

acid is, the more easily it loses a proton, H+. Two key Carboxylic acids can be reduced to the corresponding
factors that contribute to the ease of deprotonation are alcohol; the replacement of an electronegative oxygen
the polarity of the H–A bond and the size of atom A, atom with two electropositive hydrogens yields a prod-
which determines the strength of the H–A bond. Acid uct that is essentially nonacidic. The reduction of acetic
strengths are also often discussed in terms of the stabil- acid to ethanol using LiAlH4 (lithium aluminum hydride
ity of the conjugate base. or LAH), and ether is an example of such a reaction.
Caution is advised against simply classifying “cos- H H H
metic peels” for acids with pKa > 3 and “medical peels”
O LAH
for acids with pKa < 3, because some acids like phenol C
H C C H C OH
can be toxic substances even with a pKa > 3. OH ether
Polarity and the Inductive Effect H H H

The polarity of the H–A bond is the first factor contribut- The pKa for ethanol is 16, compared with 4.76 for
ing to acid strength. acetic acid.
As the electron density on hydrogen decreases, it
becomes more acidic. Moving from left to right across a Atomic Radius and Bond Strength
row on the periodic table, elements become more elec- The size of the atom A or atomic radius is the second fac-
tronegative (excluding the noble gases). tor contributing to acid strength.
In several compound classes, collectively called car- Moving down a column on the periodic table, atoms
bon acids, the C–H bond can be sufficiently acidic for become less electronegative but also significantly larger,
proton removal. Inactivated C–H bonds are found in and the size of the atom tends to dominate its acidity
alkanes and are not adjacent to a heteroatom (O, N, Si, when sharing a bond to hydrogen.
etc.). Such bonds usually only participate in radical sub- Hydrogen sulfide, H2S, is a stronger acid than water,
stitution. even though oxygen is more electronegative than sulfur.
Polarity refers to the distribution of electrons in a This is because sulfur is larger than oxygen and the H–S
bond, the region of space between two atomic nuclei bond is more easily broken than the H–O bond.
where a pair of electrons is shared. When two atoms Another factor that contributes to the ability of an
have roughly the same electronegativity (ability to acid to lose a proton is the strength of the bond between
attract electrons), the electrons are shared evenly and the acidic hydrogen and the atom that bears it. This, in
spend equal time on either end of the bond. When turn, is dependent on the size of the atoms sharing the
there is a significant difference in electronegativities of bond. For an acid HA, as the size of atom A increases, the
two bonded atoms, the electrons spend more time near strength of the bond decreases, meaning that it is more
the nucleus of the more electronegative element and an easily broken, and the strength of the acid increases.
electrical dipole, or separation of charges, occurs, such
that there is a partial negative charge localized on the Chemical Characteristics
electronegative element and a partial positive charge on It is important to keep in mind the difference between
the electropositive element. Hydrogen is an electropos- monoprotic acids (having one unique pKa) and polyprotic
itive element and accumulates a slightly positive charge acids (having two or more pKa).
when it is bonded to an electronegative element such as
oxygen or chlorine. Monoprotic Acids
The electronegative element need not be directly Monoprotic acids are those acids that are able to donate
bonded to the acidic hydrogen to increase its acidity. one proton per molecule during the process of disso-
An electronegative atom can pull electron density out ciation (sometimes called ionization), as shown below
of an acidic bond through the inductive effect. The elec- (symbolized by HA):
tron-withdrawing ability diminishes quickly as the elec-
HA(aq)+ H 2O(1) ⇌ H 3O + (aq)+A–(aq)Ka
tronegative atom moves away from the acidic bond.
Carboxylic acids are organic acids that contain an Common examples of monoprotic acids in organic
acidic hydroxyl group and a carbonyl (C–O bond). acids indicate the presence of one carboxyl group,
 CHAPTER 1 The Chemistry of Peels: A Hypothesis of Mechanism of Action 5

and mostly these acids are known as monocarboxylic

acid. Examples in organic acids include acetic acid
(CH3COOH), glycolic acid, and lactic acid.

Two dissociations mean that such acids can gen-

erate two peelings, depending on the pH, with the
second one less acidic than the first one. In this case,
we consider one peeling reaction per one dissocia-
tion.
A triprotic acid (H3A) can undergo one, two, or
three dissociations and has three dissociation constants,
where Ka1 > Ka2 > Ka3.
Polyprotic Acids H 3A (aq) + H 2O ( l ) ⇌ H 3O +(aq) + H 2A – (aq) K a1
Polyprotic acids are able to donate more than one pro-
ton per acid molecule, in contrast to monoprotic acids 2A (aq) H 2O ( l ) H 3O (aq) HA (aq) K a2
that only donate one proton per molecule. Specific types
of polyprotic acids have more specific names, such HA2 – (aq) + H 2O( l ) ⇌ H 3O + (aq) + A3 – (aq) K a3
as diprotic acid (two potential protons to donate) and
An organic example of a triprotic acid is citric acid,
triprotic acid (three potential protons to donate).
which can successively lose three protons to finally form
A diprotic acid (here symbolized by H2A) can
the citrate ion. Even though the positions of the protons
undergo one or two dissociations depending on the pH.
on the original molecule may be equivalent, the succes-
Each dissociation has its own dissociation constant, Ka1
sive Ka values will differ, because it is energetically less
and Ka2.
favorable to lose a proton if the conjugate base is more
H 2A (aq) + H 2O (1) ⇌ H 3O + (aq) + HA− (aq) K a1 negatively charged.
HA− (aq) + H 2O( l ) ⇌ H 3O +(aq) + A2 −(aq) K a2
The first dissociation constant is typically greater than
the second; i.e., Ka1 > Ka2. For example, the weak unstable
carbonic acid (H2CO3) can lose one proton to form bicar-
bonate anion (HCO3−) and lose a second to form carbon-
ate anion (CO32−). Both Ka values are small, but Ka1 > Ka2.
Weak Acid–Weak Base Equilibria
Diprotic acids used for peelings are malic, tartaric,
and azelaic acids. To lose a proton, it is necessary that the pH of the system
rise above the pKa of the protonated acid. The decreased
concentration of H+ in that basic solution shifts the
equilibrium toward the conjugate base form (the depro-
tonated form of the acid). In lower-pH (more acidic)
solutions, there is a high enough H+ concentration in
the solution to cause the acid to remain in its protonated
6 PART 1 Introductory Chapters

form, or to protonate its conjugate base (the deproton- In this equation [A−] is the concentration of the
ated form). conjugate base and [HA] is the concentration of the
Solutions of weak acids and salts of their conjugate acid. It follows that when the concentrations of acid
bases form buffer solutions. and conjugate base are equal, often described as
half-neutralization, pH = pKa. In general, the pH of
Buffer Solution a buffer solution may be easily calculated, knowing
A buffer solution is an aqueous solution consisting of the composition of the mixture, by means of an ICE
a mixture of a weak acid and its conjugate base or a table. An ICE (initial, change, equilibrium) table is
weak base and its conjugate acid. The property of buffer a simple matrix formalism that used to simplify the
solutions is that the pH of the solution changes very calculations in reversible equilibrium reactions (e.g.,
little when a small amount of acid or base is added to weak acids and weak bases or complex ion forma-
it. Buffer solutions are used as a means of keeping pH tion).
at a nearly constant value in a wide variety of chemi- One should remember that the calculated pH may be
cal applications. Many life forms thrive only in a rela- different from measured pH.
tively small pH range; an example of a buffer solution
is blood. Buffer Capacity
Buffer capacity (Fig. 1.1) is a quantitative measure of
Le Chatelier’s Principle the resistance of a buffer solution to pH change with the
In a solution there is an equilibrium between a weak addition of hydroxide ions. It can be defined as follows:
acid, HA, and its conjugate base, A−: dn
Buffer capacity=
+ – d (pH)
HA + H 2O ⇌ H 3O + A
• W hen hydrogen ions (H+) are added to the solution, where dn is an infinitesimal amount of added base
equilibrium moves to the left, as there are hydrogen and d(pH) is the resulting infinitesimal change in
ions (H+ or H3O+) on the right-hand side of the equi- pH. With this definition the buffer capacity can be
librium expression. expressed as:
• When hydroxide ions (OH−) are added to the solu- dn Kw CA K a [H + ]
tion, equilibrium moves to the right, as hydrogen =2.303 + [H + ] + 2
d ( pH) [H + ] (K a + [H + ])
ions are removed in the reaction (H+ + OH− →
H2O). where Kw is the self-ionization constant of water and
Thus, in both cases, some of the added reagent is con- CA is the analytical concentration of the acid, equal
sumed in shifting the equilibrium in accordance with Le to [HA] + [A−]. The term Kw/[H+] becomes significant
Chatelier’s principle, and the pH changes by less than it at pH greater than about 11.5, and the second term
would if the solution were not buffered. becomes significant at pH less than about 2. Both these
terms are properties of water and are independent of
Henderson–Hasselbach Equation the weak acid. Considering the third term, it follows
The acid dissociation constant for a weak acid, HA, is that:
defined as: 1. Buffer capacity of a weak acid reaches its maximum
value when pH = pKa.
[H + ] [A − ] 2. At pH = pKa ± 1 the buffer capacity falls to 33%
Ka =
[HA] of the maximum value. This is the approximate
Simple manipulation with logarithms gives the Hen- range within which buffering by a weak acid is
derson–Hasselbach equation, which describes pH in effective. Note: at pH = pKa − 1, the Hender-
terms of pKa: son–Hasselbach equation shows that the ratio
[HA]:[A−] is 10:1.
[A − ] 3. Buffer capacity is directly proportional to the analyt-
pH =pK a + log10
[HA] ical concentration of the acid.
 CHAPTER 1 The Chemistry of Peels: A Hypothesis of Mechanism of Action 7

of water. A salt is also formed. In nonaqueous reactions,

100
water is not always formed; however, there is always a
donation of protons (see Brønsted–Lowry acid–base
80 theory).
Buffer capacity (%)

Often, neutralization reactions are exothermic, giving

60 out heat to the surroundings (the enthalpy of neutraliza-
tion). On the other hand, an example of endothermic
40 neutralization is the reaction between sodium bicarbon-
ate (baking soda) and any weak acid—for example, ace-
20
tic acid (vinegar).
Neutralization of the chemical peeling agent is an
important step, the timing of which is determined by
0
either the frost in the skin or how much contact time
4 5 6 7 8 9 10 the peel has with the skin. Neutralization is achieved
pH
by a majority of peelers applying cold water or wet,
cool towels to the face following the frost. According
Fig. 1.1 Buffer capacity for pKa = 7 as a percentage of maxi- to physical chemistry, using water just after the frost
mum. provokes an exothermic reaction that can provoke
a “cold” burn. Other neutralizing agents that can be
used include bicarbonate spray or soapless cleansers.
Current Applications of Buffer Solutions Peeling agents for which this neutralization step is less
Their resistance to changes in pH makes buffer solutions important include salicylic acid, Jessner’s solution,
very useful for chemical manufacturing and essential for TCA, and phenol.
many biochemical processes. The ideal buffer for a par- In partially neutralized alpha-hydroxy acid (AHA)
ticular pH has a pKa equal to that pH, since such a solu- solutions, the acid and a lesser amount of base are
tion has maximum buffer capacity. combined in a reversible chemical reaction that yields
Buffer solutions are necessary to keep the correct unneutralized acid and a salt.
physiological pH for enzymes in many organisms to The resulting solution has less free acid and a higher
work. A buffer of carbonic acid (H2CO3) and bicarbon- pH than a solution that has not been neutralized. In par-
ate (HCO3−) is present in blood plasma, to maintain a tially neutralized formulations, the salt functions as a
pH between 7.35 and 7.45. reservoir of acid that is available for second-phase pen-
The majority of biological samples used in research etration. This means that partially neutralized formulas
are made in buffers, specifically phosphate-buffered can deliver as much, if not more, AHA than free acid
saline (PBS) at pH 7.4. formulas, but in a safer, “time-released” manner. There-
Buffered TCA are more likely to create dyschromias. fore the use of partially neutralized glycolic acid solu-
tions seems prudent, because they have a better safety
Useful Buffer Mixtures profile than low-pH solutions containing only free gly-
• Citric acid, sodium citrate, pH range 2.5 to 5.6. colic acid.
• Acetic acid, sodium acetate, pH range 3.7 to 5.6. Clinical studies have shown that a partially neutral-
ized lactic acid preparation improves the skin, both in
Neutralization appearance and histologically. Other studies using skin
There is among physicians a big confusion between tissue cultures showed that partially neutralized glycolic
a buffered peel (see above) and a neutralized peel. In acid stimulates fibroblast proliferation—an index of tis-
chemistry, neutralization is a chemical reaction whereby sue regeneration. Looking at electrical conductance of
an acid and a base react to form water and a salt. the skin (an indicator of water content or moisturiza-
In an aqueous solution, solvated hydrogen ions tion), higher pH products (those that have been par-
(hydronium ions, H3O+) react with hydroxide ions tially neutralized) are better moisturizers than lower pH
(OH−) formed from the alkali to make two molecules preparations.
8 PART 1 Introductory Chapters

0.45 mm 0.06 mm 0.6 mm

Stratum papillare

Stratum reticulare

Fig. 1.2 Anatomy of the skin with penetration depths of the various peels: green, superficial peels; blue,
medium-depth peels; and red, deep peels.

The most important molecule in the epidermis is a

ANATOMY OF THE SKIN fibrous and corneal protein, keratin, that protects and
Like the whole human organism, the skin can be con- takes part, through its continuous production by the
sidered an aqueous solution into which are dissolved a keratinocytes, in the complete replacement of the epi-
certain number of molecules (Fig. 1.2). These are mol- dermis every 27 days.
ecules of proteins, lipids, and carbohydrates in variable The most important molecules of the dermis are
quantities and proportions. collagen, elastin, GAGs, and the proteoglycans. Col-
There is more water in the dermis than in the epider- lagen and elastin are proteins, whereas GAGs (e.g.,
mis. This is due to the presence of blood, glycosamino- hyaluronic acid) and the proteoglycans are biolog-
glycans (GAGs), and lymph in the dermis, all of which ical polymers formed mainly by sugars that retain
have a high water content, as well as the fact that the water.
epidermis is in contact with a more or less dehydrated Collagen constitutes the skin’s structural resource
environment. and is the most abundant protein in the human body. It
There are more proteins (keratin) in the epidermis is formed mainly by glycine, proline, and hydroxypro-
than in the dermis, whereas more carbohydrates and line. It is one of the most resistant natural proteins and
lipids exist in the dermis, and there are even more in the helps give the skin structural support. Elastin is similar
subcutaneous layer than in the dermis. to collagen, but it is an extensible protein responsible for