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CLINICAL PRACTICE

Physiology of

Wound HealingBy Frances Strodtbeck, DNS, RNC, NNP

Abstract

Despite the emphasis placed on skin

care, hospitalized infants often

experience injury to their skin.

Although skin injuries vary, they have a

common innate mechanism for repair

and healing. Wound healing is a

physiologic process that involves a

series of sequential yet overlapping

stages. The first stage, hemostasis,

occurs immediately at the time of

injury. During hemostasis, a

provisional matrix seals the injury site

and initiates the process of wound

healing. The second stage,

inflammation, is triggered by a variety

of mediators released from injured

tissue cells and capillaries, activated

platelets and their cytokines, and the

by-products of hemostasis. During the

third stage, the wound surface is

covered with new skin and vascular and

structural integrity are restored as

granulation tissue fills the defect. The

final stage, remodeling, is responsible

for maturation of the granulation tissue

into mature connective tissue and/or

scar. A thorough understanding of

wound healing physiology is an

important prerequisite to providing care

that optimizes wound healing and

prevents unnecessary complications.

Many of the current wound care

practices are based on tradition rather

than scientific knowledge. As the

interface between the infant and the

environment, nurses are in an ideal

position to evaluate the soundness of

these wound care practices.Physiologic-based care strategies to

enhance wound healing are proposed.

Copyright c 2001 by

W.B. Saunders Company

From the Advanced Neonatal Nursing

Program, Baylor University, Louise Herrington

School of Nursing, Dallas, TX.

Address reprint requests to Frances Strodtbeck,

DNS, RNC, NNP, Associate Professor and

Coordinator, Advanced Neonatal Nursing

Program, Baylor University, Louise Herrington

School of Nursing, 3700 Worth St, Dallas,

TX 75246.

c2001 by W.B. Saunders Company1527-3369/01/0101-0555$35.00/0

doi: 10.1053/nbin.2001.23176

Despite the current emphasis placed on skin care, newborns and infants

who are hospitalized in the intensive care units often experience injury

to their skin. Although skin injuries vary in nature, they have a com-

mon innate mechanism for repair and healing. When triggered by an injury, this

mechanism is an elaborate cascade of physiologic events designed to repair and

ultimately heal the skin. Ironically, this process, whichis so important for survivalof the species, begins at birth with the severing of the umbilical cord. Although

the amount of scientific information regarding wound healing is increasing, there

is limited literature on wound healing in newborns and infants. This article de-

scribes thephysiologic process of wound healing, summarizes thecurrent state of

knowledge on wound healing, and discusses the implications for newborn/infant

skin care practices. A thorough understanding of wound healing and the factors

that promote or interfere with the process are essential to develop appropriate

clinical interventions for newborns and infants.

The first step in understanding wound healing is to clarify terminology. Ac-

cording to the Wound Healing Society, a wound is the disruption of normal

anatomic structure and function1 that can be classified into 1 of 2 categories

based on the nature of the repair process. These categories are acute and chronic

wounds. Acute wounds are typically tissue injuries caused by cuts or surgical in-cisions that complete the wound healing process within the expected time frame.

In contrast, chronic wounds are tissue injuries that heal sluggishly because of

repeated insults to the tissues and/or other underlying pathophysiology that in-

terferes with the expected time line and orderly sequence of wound healing.2,3

Wounds are also named by various descriptors reflective of the nature of the

injury, ie, burn, laceration, and so on. Table 1 provides a summary of common

definitions of wounds. Much of what is known about the physiology of wound

healing has been learned from the study of acute wound healing models.2

Healing is defined by the Wound Healing Society as a complex dynamic

process that results in the restoration of anatomic continuity and function. 1

Surgeons typically divide healing into categories based on the anticipated nature

of the repair process. The categories of healing by primary or secondary intention

and delayed primary repair are described in Table 2 and shown in Fig 1.

Wound Healing

Wound healing is a physiologic process involving a series of sequentialyet overlapping stages. There are anywhere from 3 to 5 stages of woundhealing, depending on how the various biologic mechanisms are linked. For the

purposes of this article, thegeneral stagesof wound healing describedby Schultz3

are used (Fig 2).

The first stage, hemostasis, occurs immediately at the time of injury and is

usually completed within hours. The second stage, inflammation, begins shortly

Newborn and Infant Nursing Reviews, Vol 1, No 1 (March), 2001: pp 4352 43


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44 Frances Strodtbeck

Table 1. Definitions of Wounds

Term Definition

Wound Disturbance in the normal skin anatomy and function; tissue injury resulting in the loss of continuity of epithelium

with or without the loss of underlying connective tissue 3

Acute wound Tissue injury that normally proceeds through an orderly and timely reparative process that results in sustained

restoration of anatomic and functional integrity 1

Chronic wound Tissue injury that fails to proceed through an orderly and timely reparative process to produce anatomic and

functional integrity or proceeds through the repair process without establishing a sustained anatomic and

functional result 1

Abrasion Loss of superficial skin (usually epithelium) that exposes nerve endings resulting in a painful injury; plasma and/or

blood loss similar to a burn can result from serious abrasions3

Contusion Severe laceration resulting in tissue loss and separation of tissue layers3

Incision Injury with no tissue loss and minimal tissue damage caused by a sharp object such as a scalpel or knife3

Laceration Nonsurgical injury in conjuction with some type of trauma, resulting in tissue loss and damage3

Ulcer Loss of an epithelial surface together with a variable degree of underlying connective tissue 3

after hemostasis and is usually completed within the first

24 to 72 hours after injury;4 however, it may last as long as

5 to 7 days after injury. Proliferation and repair, the third

stage, typically occurs 1 to 3 weeks after injury. The fourth

and final stage, remodeling, begins approximately 3 weeks

after injury and may take anywhere from months to sev-

eral years to achieve physiologic completion.2,57 Thus,

it is important to note that although the skin seems intact

withindays to severalweeksafter an injury, thetissue under-

neath is still vulnerable to damage as it undergoes the final

stages of wound healing. The reader should also remem-ber the time lines previously described are based on adult

models. Although there are no published newborn/infant

data, some investigators suggest children heal faster than

adults.78

Stage 1: Hemostasis

At the time of skin injury, bleeding usually occurs.

Not only does this bleeding serve to flush microorgan-

Table 2. Definitions of Healing

Term Definition

Healing Restoration of the normal structure and function of skin/tissue2

Primary intention Healing after a clean injury, such as an incision, in which there is minimal epithelialization and new tissue

needed to repair the skin defect; skin edges are approximated with sutures, staples, or adhesive, enabling

closure to occur quickly with minimal scarring7,19

Secondary

intention

Healing associated with a large and/or deep wound in which the tissue edges cannot be approximated; the

wound depth determines the degree of new tissue matrix and epidermal surface needed for complete

closure; this process is often lengthier than healing by primary intention and can be associated with

substantial scarring7,19

Delayed primary

(tertiary)

intention

Healing associated with wounds that are usually infected or dehisced surgical wounds; healing is promoted by

leaving the wound open for a prescribed period of time to treat the contamination or infection and to allow

for growth of new tissue before approximating the skin edges for a primary closure7,19

isms or antigens from the wound, but it also activates

hemostasis. Hemostasis is initiated by a variety of fac-

tors. Clotting factors released by injured skin cells acti-

vate the extrinsic clotting cascade.56 Platelet aggregation

and the exposureof collagenfrom the damaged skins initiate

the intrinsic clotting cascade and trigger platelet-mediated

vasoconstriction.6 This vasoconstriction prevents the fur-

ther loss of blood while the fibrin clot forms a temporary

seal over the injury site and prevents the influx of microor-

ganisms.

In addition to its protective role, hemostasis is criticalto successful wound healing.9 The fibrin clot is a provi-

sional matrix or scaffold that guides and supports the in-

flux of fibroblast and keratinocytes.10 This provisional ma-

trix is composed of fibrin and fibronectin. Fibronectin is a

multipurpose adhesion protein with an affinity for fibrin. It

circulates in blood and is also found in other tissues. Fi-

bronectinparticipates in wound healing in a variety of ways.

It serves as a chemoattractant for the migration of wound

repair cells and as a template for the deposition of collagen


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Physiology of Wound Healing 45

Fig 1. (A) Wound healing by primary intention, such as with a

surgical incision (left). Wound edges are pulled together and ap-

proximated with sutures, staples, or adhesive tapes, and healing

occurs mainly by connective tissue deposition. (B) Wound heal-

ing by secondary intention. Wound edges are not approximated,

and healing occurs by granulation tissue formation and contrac-

tion of the wound edges. (C) Wound healing by tertiary (delayed

primary) intention. Wound is kept open for several days. The su-

perficial wound edges arethen approximated, and thecenter of the

wound heals by granulation tissue formation. (Reprinted with per-

mission from Trott AT: Wounds and Lacerations [ed 2]. St Louis,

MO, Mosby, 1997)

fibers. It also participates in wound debridement by degrad-

ing extracellular matrix (ECM) debris and activating thephagocytic properties of macrophages.10

Platelet activation results in degranulation and the re-

lease of a variety of potent cytokines that induce the process

of tissue repair and activate additional immune defenses.

By attaching to exposed collagen fibers in the wound, ac-

tivated platelets also stimulate the production of new ECM

substances.10 The specific mechanisms mediated by these

cytokines include the recruitment of inflammatory cells to

the injury site (activation of the inflammatory response) and

the proliferation of new cells (epithelialization) and blood

vessels (angiogenesis) at the injury site. Because of the po-

tency of these cytokines and the specificity of their action

in the microenvironment of the injury site, minuscule quan-

tities of the cytokines are needed.2

One of the most interesting groups of cytokines pro-duced is platelet-mediated growth factors. These growth

factors are responsible for a variety of molecular processes

includingthe influx of fibroblasts and keratinocytes, the syn-

thesis of collagen and other ECM proteins, the regulation

of cell movement within the wound microenvironment, the

directed growth of new capillaries and vascular beds, and

the synthesis of enzymes used to reshape the newly formed

connective tissue.11,12 A listing of the specific growth fac-

tors and their functions can be found in Table 3.

Stage 2: Inflammation

The second stage of wound healing is inflammation. Theinflammatory response is triggered by a variety of media-

tors released from injured tissue cells and capillaries, acti-

vated platelets and their cytokines, and the by-products of

hemostasis. Within minutes after the injury, neutrophils ar-

rive to contain any microorganisms present in the wound.2,9

Neutrophils also initiate wound repair by activating local fi-

broblasts and epithelial cells.13 Although other white cells,

including monocytes, lymphocytes, and plasma cells, mi-

grate to the injury site, neutrophils predominant for the first

few days and then disappear unless the wound becomes

infected.2,6 In the presence of infection, neutrophil infiltra-

tion continues until the infection is controlled.

In the absence of infection, the existing monocytesdiffer-

entiate into macrophages and become the major phagocytic

cellattheinjurysite.5 Macrophageinfiltrationpredominates

for the remainder of the wound healing process. In addition

to ingesting surviving microorganisms, dead neutrophils,

the fibrin clot, and other cellular debris, macrophages syn-

thesize nitric oxide and secrete cytokines to initiate wound

repair. Although the exact nature of nitric oxides involve-

ment in wound healing is unknown, animal studies sug-

gest an important role in the regulation of keratinocytes, ie,

low concentrations of nitric oxide increased cell prolifera-

tion, whereas high concentrations resulted in increased cell

differentiation.14,15

According to Haas,4 the macrophage is the transition

cell between wound inflammation and wound repair be-

cause of its essential role in wound healing. As the need for

immune defense diminishes, macrophages take over regu-

lation of the wound healing process. The importance of this

role is underscored by studies that have shown that wounds

can heal normally in the absence of neutrophils but not in

the absence of macrophages.16

Like the platelet, the macrophage synthesizes a variety

of cytokines including growth factors involved in the migra-

tion, proliferation, and organization of new connective tis-

sue and vascular beds within the wound. Unlike the platelet


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Fig 2. Temporal relationship between the multiple processes occurring in dermal wound healing. (Reprinted with permission 6)

that releases stored cytokines, the macrophage is able to

synthesize and secrete cytokines over time, assuring con-

tinuation of the process of tissue repair.2,11,12

Macrophages also produce special enzymes called ma-

trix metalloproteinases or metalloproteases (MMPs).5 To

date, more than 20 unique MMPs have been identified.16

One of the best-studied enzymes is collagenase, which plays

a pivotal role in wound debridement and the shaping of new

connective tissue.

Another important mechanism in the inflammatory stage

of wound healing is activation of vasoactive substancessuch

as serotonin, bradykinin, prostaglandins, and histamine.2,4

Table 3. Platelet-Mediated Growth Factors Involved in Wound Healing

Cytokine Purpose/Function

Epidermal growth factors (EGF) Mitosis and migration of keratinocytes; stimulates wound re-epithelialization;

angiogenesis

Fibroblast growth factor (FGF) Mitosis and migration of keratinocytes and fibroblasts; stimulates collagen formation;

angiogenesis

Insulin-like growth factors (IGF-1, IGF-2) Mitosis of keratinocytes and fibroblasts

Keratinocyte growth factor (KGF) Mitosis of keratinocytes; activation of monocytes

Platelet-derived growth factor (PDGF) Chemoattractant for fibroblasts and other cells; cell proliferation; wound contraction

Transforming growth factor- (TGF-) Mitosis and migration of keratinocytes; regulation of inflammatory cells

Transforming growth factor- (TGF-) Chemoattractant for fibroblasts and macrophages; migration of keratinocytes; fibroblast

matrix synthesis and remodeling

Data from.5,911

These substances increase permeability of endothelium

within the injury site and increase perfusion to the site. In-

creased permeability facilitates infiltration by immune and

repair cells, whereas increased circulation increases oxygen

delivery. As a consequence, the temperature at the injury site

increases and fluid begins to leak into the wound. Although

clinically this results in skin erythema and edema, the

warm, moist microenvironment created within the wound is

essential for the next stage of healing.2 At the end of the in-

flammation stage of wound healing, bleeding is controlled

and the wound bed is clean. This creates the perfect envi-

ronment for the next stage of cell proliferation and repair.


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Stage 3: Proliferation and Repair

Thespecific mechanisms of stage 3 areaimed at coveringthe wound surface with new skin (re-epithelization), restor-

ing vascularintegrity to the region (neovascularization), and

repairingthe structureintegrity of thetissue defectby filling

it with new connective tissue (granulation).2 Wound (ten-

sile) strength begins to develop during this stage. Key cells

for these processes are the fibroblast and keratinocyte.

The warm, moist microenvironment of the wound also

facilitates proliferation and repair. The leaked fluid or exu-

date is rich in cytokines that stimulate new tissue growth.

Shortly after the injury occurs, hypoxia and acidosis de-

velopwithin thewoundbed as thepartialpressure of oxygen

decreases to around 10 mm Hg, the partial pressure of car-

bon dioxide increases to 80 mm Hg, and the pH approaches6.8.18 This leads to an increase in lactate or lactic acid. Al-

though at first glance it would seem that hypoxia and acido-

sis are counterproductive to healing, these processes stimu-

late angiogenesis (growth of new blood vessels) and colla-

gen synthesis. Because lactate modulates the concentration

of a variety of enzymes involved in cell energy metabolism

and transcription, increased lactate levels stimulate collagen

synthesis within the wound. The rate of collagen secretion

is partially governed by oxygen delivery to the newly de-

veloping tissue. This in turn influences the tensile strength

of the repair.18

Neovascularization

Essential parts of any repair process are the availability of a

steadysupply of nutrientsand an intactdelivery system. The

process of restoring the vascular network is called neovas-

cularization or angiogenesis. Neovascularization is stimu-

lated by growthfactors andtissue hypoxia. At thestart of the

wound healing process, the most viable parts of the wound

arethose with accessto a vascularsupplythewound edges

and the parts in contact with the underlying dermal vascular

bed.19 This creates a hypoxic gradient between the avascu-

lar wound center and the vascularized wound borders.2 In-

creased endothelial permeability allows nutrients to escapefrom the intact vascular bed into the interstitium and injury

site. This creates a nutrient-rich microenvironment that sus-

tains the developing repair process until neovascularization

can occur.

Closure of the wound surface is necessary to create a

hypoxic wound environment. The fibrin clot formed during

hemostasis provides a temporary cover that is eventually re-

placed by new epidermal cells. This creates a closed system

in which angiogenesis can proceed.10 Hypoxia is thought to

induce macrophages into secreting angiogenic growth fac-

tors. Lactic acidosis also stimulates angiogenesis.18 Platelet

and macrophage-derived growth factors, such as fibroblast

growth factor and vascular endothelial growth factor, are re-

leased by endothelial cells and stimulate angiogenesis along

the wound edges.9 New blood vessels bud or sprout fromintact vessels in the underlying dermis.19 The new capillary

buds join to form capillary loops thereby establishing blood

flow within the wound.10 New sprouts or buds extend from

the capillary loops further into the wound environment. The

process of arborization is thus stimulated by hypoxia within

the wound environment and results in the growth of new

vessels throughout the wound.

Another essential requirement of neovascularization is

the formation of an appropriate ECM with an adequate

supply of oxygen. Collagen deposition is critical for aor-

tic endothelial cell migration.10 Several key enzymes that

are oxygen dependent control collagen synthesis. Because

these rate-limiting enzymes extract about 1 mL of oxygenper 100 mL of blood,18 oxygen delivery to the developing

tissueis more critical than thetotalamount of oxygen. Thus,

perfusion to the site of injury is the major determinant of

oxygenation.10

Re-epithelization

Re-epithelization of a wound occurs when keratinocytes

completely cover the surface of the skin defect. As the

largest group of epithelial cells within the epidermis, ker-

atinocytes along the wound edges undergo intense mi-

totic activity. Keratinocytes, stimulated by locally released

growth factors, proliferate and begin their migration across

the wound bed within 12 to 24 hours after injury.19,20 Be-

cause the site of proliferation is usually proximal to the

injury, the new keratinocytes must migrate to the repair

site. Migration requires a fluid environment2 and involves a

complex series of steps controlled by a chemotactic gradi-

ent generated by various growth factors. In the absence of a

fluid surface, the keratinocyte secretes proteolytic enzymes

that enable it to burrow downward to find the necessary

moisture for migration (Fig 3).2,21

The first step of migration involves separation of the

keratinocytes from each other and their anchors to the cellbasement membrane.22 The migrating keratinocyte then un-

dergoes transformation by elongating itself in the direc-

tion growth is needed. The leading edge of the elongated

keratinocyte attaches to a new spot in the wound bed. The

cell then contracts, pulling itself forward across the wound

surface. This process is repeated until the migrating cells

from opposing sides of the wound touch each other. At the

pointof contact, migrationceasesin a process known as con-

tact inhibition.22,23 Another process used for keratinocyte

migration is leapfrogging (Fig 4). Leapfrogging occurs

when a single cell moves only 2 or 3 cell lengths and then

stops, allowing consecutive cells to climb over.2


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Fig 3. Diagram of migration of epidermal cells in (A) moist environment and (B) dry environment. (Reprinted with permission 2)

As keratinocytes proliferate and migrate across the

wound, they also participate in shaping the ECM by ex-

pressing surface markers that enhance migration across the

matrix.10 Supporting structures are selectively degraded

and resynthesized to provide temporary anchors during

the migratory phase. Once migration is complete, the ker-

atinocytes stabilizethemselves by forming firm attachments

to each other and the new basement membrane.10,23 Migra-

tion proceeds from the wound edges towards the center in

a centripetal manner.9,10

When the skin surface is completely covered with new

epidermal cells, the wound is considered closed. Early clo-

sure of an open wound with a viable epidermis is essential

because it induces remodeling of the underlying tissue. The

chance of developing hypertrophic scar tissue is also greatly

reduced by early wound closure.19

Fig4. Epidermalcell migrationvia development of pseudopod and

leapfrogging. (Reprinted with permission2)

Granulation

The third and final mechanism of proliferation and repair is

the development of granulation tissue. Granulation tissue,

a transitional substance that replaces the fibrin/fibronectin

matrix, begins to appearabout4 days after injury.10,19 Gran-

ulation occursas thefibrinclot scaffoldis replaced with new

tissue rich in hyaluronan (hyaluronic acid), fibronectin, and

other ECM compounds. Because granulation tissue is very

active metabolically and supports the proliferation of a va-

riety of cells and proteins, it is also highly vascular.19 This

accounts for its classic pinkish-red appearance.

The predominant cell type found in granulation tissue is

the fibroblast.19 Fibroblasts are dermal cells that produce

collagen and numerous other substances that comprise the

ECM. ECM is composed of substances that promote adhe-

sion and migration (fibronectin); glycoaminoglycans that

promote tissue hydration (hyaluronan); proteoglycans or

matrix proteins that are involved in the regulation, migra-

tion, storage, and expression of a variety of substances in-

cluding growth factors, enzymes, and coagulation proteins

(chondroitin sulfate); and glycoproteins that provide tissuestrength and resiliency (collagens, elastin).10,24 Fibroblast

migration and proliferation are triggered by signals from

platelet-derived growth factor, transforming growth factor,

fibroblast growth factor, and complement C5a released by

activated cells of the inflammatory response.19

The influx of fibroblasts causes the provisional matrix

of fibrin/fibronectin to be degraded and replaced with a

new matrix. After migration to the wound, fibroblasts begin

to synthesize the proteins hyaluronan and fibronectin.10,19

This new matrix is composed of fibronectin and collagen

that provides a scaffold for cell migration and organization,

hyaluronan that facilitates migration by providing a low


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impedance medium, and macrophages and other substances

that provide essential cytokines.10

Normal dermal fibroblasts and the fibroblasts involvedin theformation of granulation tissue differin both structure

and function. Wound fibroblasts tend to be involved in col-

lagen synthesis rather than proliferation.2 These fibroblasts

produce and release proteoglycans, glycosaminoglycans,

and collagen.6 They also participate in theprocess of wound

contraction after differentiation into myofibroblasts.25

Differentiated fibroblasts contain contractile proteins

such as actin.6 Myofibroblasts are arranged in densely

packed groups. This arrangement, in conjunction with

their special contractile properties, allows the myofibrob-

last to pull wound edges together through the process of

contraction.25 Contraction decreases healing time because

it decreases the size of the wound and reduces the amount ofECM needed to repair the defect.26 Contraction also facili-

tates re-epithelization by shortening the distance migrating

keratinocytes must travel.10

The structure and composition of granulation tissue un-

dergoes constant change as it matures. Although collagen

becomes the predominant protein, there are at least 19 dif-

ferent types of collagen.24 The type of collagen present in

a tissue varies with the tissue. For example, skin collagen

is 80% type I and 20% type III. 19,24

Thenew granulation tissue contains type I, III, andV col-

lagen fibers.24 Thirty percent of the collagen is type III col-

lagen, which does not contribute to restoring tensile strength

in the wound.19 At 3 weeks after injury, the healing wound

has approximately 20% of its final strength.2,19

Stage 4: Remodeling

The final stage of wound healing is remodeling or mat-

uration of the granulation tissue into mature connective tis-

sue and/or scar. The wound also develops its final strength

during this stage of wound healing.25 The key cells for re-

modeling are macrophages and fibroblasts. ECM reshaping

by cross-linking collagens, cell maturation, and program

cell death or apoptosis are the mechanisms used in woundremodeling.10 Collagen synthesis peaks around 5 days af-

ter injury but continues for weeks or months. 2 During this

time, collagen andECM tissue continue to be deposited into

the wound, whereas the developing connective tissue is re-

shaped by cell maturation and apoptosis. Although wound

strength increases, it never achieves more than 80% of the

preinjury strength.2,5,27

Wound remodeling begins at different times in different

regions. ECM-bound growth factors and MMPs are acti-

vated by macrophages and fibroblasts, resulting in degrada-

tion of the matrix and differentiation of cells.28 Collagen is

first released in precursorformas a triplehelix protein called

procollagen. Procollagen is then formed into fibers that are

arranged in parallel fashion and cross-linked to form thicker

and stronger strands.2 This process converts the loose gran-ulation tissue matrix into a stable ECM.3 There are substan-

tial differences between the repaired tissue and noninjured

skin. The new connective tissue is not as well anchored to

the underlying connective tissue matrix and is thicker than

normal skin.19

During this time, fibronectin and hyaluronan are re-

placed, collagen bundles grow in size and strength, neovas-

cularization ceases, and metabolic activity within the ECM

declines. Type III collagen decreases from 30% to 10%,

with the net result a much stronger tissue.19 The density of

cells, such as macrophages, keratinocytes, fibroblasts, and

myofibroblasts, is reduced by apoptosis.10,19 Keratinocytes

are the first cells to undergo programmed cell death; my-ofibroblasts are the second.10 Remodeling is thus a balance

between the synthesis of new collagen and the degradation

of old.4 Remodeling is regulated by fibroblasts through the

synthesis of ECM components and MMPs that control cell

differentiation. 28 As the wound healing process is switched

off, the new connective tissue matures and changes from

pinkish-red to a white color.7

Clinical Implications

Although there is a paucity of literature on wound heal-

ing in newborns/infants, there is no reason to ignore

scientific knowledge when developing management strate-

gies for newbornsand infants with skin injuries. A thorough

understanding of wound healing physiology is an important

prerequisite to providing care that optimizes wound heal-

ing and prevents unnecessary complications. Many of the

current wound care practices are based on tradition and

may not be grounded in scientific soundness. As the inter-

face between the infant and the environment, nurses are in

an ideal position to evaluate the soundness of wound care

practices. Advanced-practice nurses have the added advan-

tage of being able to bridge medical and nursing care and

are in an ideal position to direct changes in wound manage-ment care.

Obviously, the most important wound management ac-

tivity is the prevention of skin injury; however, that is not

always possible. Some infants require procedures, such as

surgery, thatnecessitatean incision.Other infants may expe-

rience extravasation of intravenous fluids, resulting in skin

injury. The clinician who understands the science of wound

healing will be able to prevent complications and maximize

the infants ability to heal.

Because preventing skin injury is not always realistic,

it is important to provide care that optimizes the infants

ability to heal him/herself. Care should be focused on


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Table 4. Strategies to Promote Wound Healing in Newborns/Infants

Wound Healing

Care Strategy Event Trageted Scientific Rationale

Maintain normal serum

calcium levels

Collagen maturation; wound

contraction

Actin-myosin contractility is calcium dependent39

Maintain normal perfusion Metabolic activities within

the wound

microenvironment

Maximizes oxygen delivery to the wound bed

Maintain adequate

oxygenation

Collagen synthesis;

fibroblast proliferation;

keratinocyte mitosis

Collagen synthesis and secretion depends on oxygen-dependent

enzyme reactions19; increases tissue resistance to infection2

Maintain iron stores and/or

provide ferrous iron

Collagen synthesis and

remodeling

Ferrous iron is a co-factor for collagen hydroxylation reactions19

Cover injuries with an

occlusive hydrocolloid

dressing

Keratinocyte migration;

sequestering of growth

factors

The hydrocolloid dressing provides a temporary cover under which

wound exudate can collect; this allows the wound bed to be bathed

with growth-factor rich fluid that facilitates keratinocyte migration;

the application of an occlusive hydrocolloid may decrease the risk

of wound infection4043

Keep the infant in a neutral

thermal environment

Inflammatory cell activity;

Leukocyte activity

Hypothermia decreases leukocyte mitotic activity44; the ideal wound

temperature is 37C44

Maintain renal function Production of granulation

tissue; Fibroblast and

keratinocyte proliferation

Animal data shows that acute renal failure leads to inadequate

granulation tissue production4547; chronic renal failure is

associated with decreases in plasma fibronectin concentration37

Prevent sepsis/infections Inflammatory response;

collagen synthesis;

epithelialization

Infection prolongs the inflammatory process, which delays wound

healing; prolonged exposure to inflammatory cytokines also

produces tissue damage2

Avoid the use ofcorticosteroids

Every aspect of woundhealing

Corticosteroids have a substantial impact on every stage of woundhealing; they reduce macrophage migration, suppress the

inflammatory response decrease keratinocyte and fibroblast

proliferation, impair capillary budding, decrease ECM production,

decrease protein synthesis, delay epithelialization, and block the

release of vasoactive factors2,6,48,49

Maximize protein in

parenteral and/or enteral

nutrition

Collagen synthesis; wound

contraction and

remodeling

Additional protein is needed to meet the demands of wound

healing49,50

Provide vitamins A, and C

and B-complex vitamins

(thiamine, niacin,

riboflavin, folate, B12)

Epithelialization; collagen

synthesis; cell metabolism

Vitamin A promotes epithelial integrity; the B-complex vitamins are

important for anabolic reactions such as wound healing; vitamin C

is a co-factor for collagen synthesis and is important for normal

immune function49,50

Provide zinc and copper Collagen synthesis Zinc is a co-factor for collagen synthesis,19 epithelialization, and

fibroblast proliferation6 Copper is a co-factor for collagencross-linking reactions6

Maintain euvolemia Tissue oxygenation Normal perfusion is needed to maintain the wound microenvironment

and the developing ECM51

Provide adequate pain

management

Wound perfusion; all aspects

of wound healing

Connective tissue perfusion is sensitive to autonomic nervous

activity18; pain results in catecholamine release that can lead to

vasoconstriction and impaired wound perfusion,2 pain also

stimulates corticosteroid release that can interfere with wound

healing


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facilitating wound healing and preventing complications of

existing wounds. Physiologic-based care strategies to en-

hance wound healing are provided in Table 4.Two strategies thatdeservespecialattention are the use of

corticosteroids and wound dressings. Corticosteroids have

a profound suppressive effect on the inflammatory response

and affect every aspect of wound healing. The use of cor-

ticosteroids should be avoided in infants with serious skin

injuries and surgical infants. Animal data from Sandberg29

suggest that delaying the use of corticosteroids until after

the inflammatory stage may decrease the negative conse-

quences on wound healing. Simultaneous administration of

vitamin A during corticosteroid therapy has been shown

also to reverse the effects of steroids on wound healing.30,31

The type of wound dressing has been a controversial

subject for many years. Wound dressing preferences tendto be based on prior experience and tradition rather than

scientific data. Many clinicians advocate the use of gauze

or air-treated wounds. Allowing wounds to dry out causes

the repair process to stop.7 In a study comparing the use

of gauze dressings or air-treated wounds with the use of a

moist dressing, Eaglstein32 noted a 40% reduction in heal-

ing in the gauze or air-treated wounds. Other studies have

shown that moisture-retentive, hydrocolloid dressings pro-

mote wound healing by increasing fibrinolysis and autolysis

of necrotic tissue, facilitate the release of growth factors, re-

duce thetime to heal, andpromote angiogenesis.3335 Other

advantages reported with this type of dressing are decreases

in pain, trauma to the wound from dressing changes, the

risk of wound infection, the risk for nosocomial infections

caused by airborne transmission of microorganisms, and the

cost of care.7,21

Other studies pose intriguing questions regarding wound

management in newborns and infants. A study from Japan

showed increased fibroblast growth in cultured human cells

and venous leg ulcers in adults treated with intermittent

radiant warming.36 This raises the question, What is the

impact on wound healing when infants live in a heated in-

cubator or on a radiant warmer? Does humidification of the

environment contribute to wound healing? Mulder et al37

discuss a number of studies evaluating the impact of jaun-dice on wound healing; their conclusion is jaundiceclearly

has the potential to impair wound healing. If this is indeed

true, What is the impact of hyperbilirubinemia on wound

healing in infants? Other studies shown that theamino acids

arginine and glutamine promote wound healing by improv-

ing collagen synthesis.38,39 Should newborns and infants

with substantial wounds receive arginine and/or glutamine

supplementation? Although these questions remain unan-

swered, it is clear that there are many areas for knowledge

development in the understanding of wound healing in the

infant population.

Conclusion

Wound healing is a fascinating biologic event essentialfor human survival. Although many of the physio-logic processes have been studied in animal and adult mod-

els, little information is available regarding wound healing

in infants. Because of the immaturity of their skin, many

hospitalized infants are at high risk for skin injuries. Other

infants experience skin injury after surgery and/or inva-

sive procedures. It is essential that clinicians understand

the physiology of wound healing so they can provide com-

petent care that optimizes the infants ability to heal and

prevents further injury and/or complications.

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