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CHAPTER 9

WOUND HEALING
QUESTIONS AND ANSWERS
1. The peak number of fibroblasts in a
healing wound occurs

A. 2 days after injury


B. 6 days after injury
C. 15 days after injury
D. 60 days after injury
• Answer: B
2. Macrophages are present in the wound
starting on the 4th day after injury until
the wound is completely healed. The
primary function of the macrophages in
wound healing is

A. Intracellular killing of bacteria


B. Collagen production
C. Activation of cell proliferation
D. Modulation of the wound environment
• Answer: D
EB is classified into three major subtypes: EB simplex,
junctional EB, and dystrophic EB. The genetic defect
involves impairment in tissue adhesion within the
epidermis, basement membrane, or dermis, resulting in
tissue separation and blistering with minimal trauma.
Characteristic features of EB are blistering and
ulceration. Management of nonhealing wounds in
patients with EB is a challenge, as their nutritional
status is compromised because of oral erosions and
esophageal obstruction. Surgical interventions include
esophageal dilation and gastrostomy tube placement.
Dermal incisions must be meticulously placed to avoid
further trauma to skin. The skin requires nonadhesive
pads covered by ‘bulky’ dressing to avoid blistering.
3. Which phase of healing is most affected
by exogenous corticosteroids?

A. Initial phase of cell migration and


angiogenesis
B. Proliferative phase
C. Maturation
D. Scar remodeling
• Answer: A
Large doses or chronic usage of glucocorticoids reduce
collagen synthesis and wound strength. The major effect of
steroids is to inhibit the inflammatory phase of wound healing
(angiogenesis, neutrophil and macrophage migration, and
fibroblast proliferation) and the release of lysosomal enzymes.
The stronger the anti-inflammatory effect of the steroid
compound used, the greater the inhibitory effect on wound
healing. Steroids used after the first 3 to 4 days postinjury do
not affect wound healing as severely as when they are used in
the immediate postoperative period. Therefore, if possible,
their use should be delayed or, alternatively, forms with lesser
anti-inflammatory effects should be administered. In addition
to their effect on collagen synthesis, steroids also inhibit
epithelialization and contraction and contribute to increased
rates of wound infection, regardless of the time of
administration.
4. Which of the following should be
given to promote wound healing in
patients receiving steroids?

A. Vitamin A
B. Vitamin B1
C. Vitamin B2
D. Vitamin C
• Answer: A
Steroid-delayed healing of cutaneous wounds can
be stimulated to epithelialize by topical application
of vitamin A. Collagen synthesis of steroid-treated
wounds also can be stimulated by vitamin A.
5. How long does protein calorie
malnutrition need to be present in
patients in order to affect wound healing?

A. Days
B. Weeks
C. 1 month
D. >3 months
• Answer: A
Two additional nutrition-related factors warrant
discussion. First, the degree of nutritional
impairment need not be longstanding in humans, as
opposed to the experimental situation. Thus,
patients with brief preoperative illnesses or reduced
nutrient intake in the period immediately preceding
the injury or operative intervention will
demonstrate impaired fibroplasias. Second, brief
and not necessarily intensive nutritional
intervention, either via the parenteral or enteral
route, can reverse or prevent the decreased
collagen deposition noted with malnutrition or with
postoperative starvation.
6. A homeless, malnourished 48-year-old
patient is admitted to the ICU after a
severe blunt injury. A reasonable daily
dose of vitamin C for this patient would
be

A. 60 mg
B. 150 mg
C. 400 mg
D. ≥1 gm
• Answer: D
Scurvy, or vitamin C deficiency, leads to a defect in wound
healing, particularly via a failure in collagen synthesis and
cross-linking. Biochemically, vitamin C is required for the
conversion of proline and lysine to hydroxyproline and
hydroxylysine, respectively. Vitamin C deficiency has also been
associated with an increased incidence of wound infection,
and if wound infection does occur, it tends to be more severe.
These effects are believed to be due to an associated
impairment in neutrophil function, decreased complement
activity, and decreased walling-off of bacteria secondary to
insufficient collagen deposition. The recommended dietary
allowance is 60 mg daily. This provides a considerable safety
margin for most healthy nonsmokers. In severely injured or
extensively burned patients this requirement may increase to
as high as 2g daily. There is no evidence that excess vitamin C
is toxic; however, there is no evidence that supertherapeutic
doses of vitamin C are of any benefit.
7. A previously healthy 18-year-old
woman is involved in a house fire and is
admitted with 60% deep partial thickness
burns to the ICU. A reasonable daily dose
of vitamin A for this patient would be

A. 1000 mg
B. 2500 mg
C. 10,000 mg
D. 25,000 mg
• Answer: D
Vitamin A deficiency impairs wound healing, whereas
supplemental vitamin A benefits wound healing in
nondeficient humans and animals. Vitamin A increases the
inflammatory response in wound healing, probably by
increasing the lability of lysosomal membranes. There is an
increased influx of macrophages, with an increase in their
activation and increased collagen synthesis. Vitamin A directly
increases collagen production and epidermal growth factor
receptors when it is added in vitro to cultured fibroblasts. As
mentioned in the section Steroids and Chemotherapeutic
Drugs, supplemental vitamin A can reverse the inhibitory
effects of corticosteroids on wound healing. Vitamin A also
can restore wound healing that has been impaired by
diabetes, tumor formation, cyclophosphamide, and radiation.
Serious injury or stress leads to increased vitamin A
requirements. In the severely injured patient, supplemental
doses of vitamin A have been recommended. Doses ranging
from 25,000 to 100,000 IU per day have been advocated.
8. The ideal time to administer
prophylactic antibiotics to a patient
undergoing a colon resection is

A. 8 hours before surgery with a dose


repeated at the time of incision
B. 2 hours before surgery with a dose
repeated at the time of incision
C. 1 hour before surgery
D. At the time of incision
• Answer: C
Antibiotic prophylaxis is most effective when
adequate concentrations of antibiotic are present in
the tissues at the time of incision, and assurance of
adequate preoperative antibiotic dosing and timing
has become a significant hospital performance
measure. Addition of antibiotics after operative
contamination has occurred is clearly ineffective in
preventing postoperative wound infections.
9. A 28-year-old patient with chronic
granulomatous disease is scheduled for
cystoscopy under general anesthesia.
Which of the following tests should be
obtained preoperatively?

A. Pulmonary function test


B. Echocardiogram
C. Abdominal ultrasound
D. EKG
• Answer: A
Chronic granulomatous disease (CGD) comprises a genetically
heterogeneous group of diseases in which the reduced nicotinamide
adenine dinucleotide phosphate–dependent oxide enzyme is eficient. This
defect impairs the intracellular killing of microorganisms, leaving the patient
liable to infection by bacteria and fungi. Afflicted patients have recurrent
infections and form granulomas, which can lead to obstruction of the gastric
antrum and genitourinary tracts and poor wound healing. Surgeons become
involved when the patient develops infectious or obstructive complications.
The nitroblue tetrazolium reduction test is used to diagnose CGD. Normal
neutrophils can reduce this compound, whereas neutrophils from affected
patients do not, facilitating the diagnosis via a colorimetric test. Clinically,
patients develop recurrent infections such as pneumonia, lymphadenitis,
hepatic abscess, and osteomyelitis. Organisms most commonly responsible
are Staphylococcus aureus, Aspergillus, Klebsiella, Serratia, or Candida.
When CGD patients require surgery, a preoperative pulmonary function test
should be considered because such patients are predisposed to obstructive
and restrictive lung disease. Wound complications, mainly infection, are
common. Sutures should be removed as late as possible because the
wounds heal slowly. Abscess drains should be left in place for a prolonged
period until the infection is completely resolved.
10. Which of the following should be
performed in a patient with a
suspected Marjolin ulcer?

A. Hyperbaric therapy for 6 weeks


B. Zinc supplementation
C. Oral tetracycline for 6 weeks
D. Biopsy
• Answer: D
Malignant transformation of chronic ulcers can
occur in any long-standing wound (Marjolin ulcer).
Any wound that does not heal for a prolonged
period of time is prone to malignant transformation.
Malignant wounds are differentiated clinically from
nonmalignant wounds by the presence of
overturned wound edges. In patients with
suspected malignant transformations, biopsy of the
wound edges must be performed to rule out
malignancy. Cancers arising de novo in chronic
wounds include both squamous and basal cell
carcinomas.
11. Which of the following is
considered the most effective therapy
for venous stasis ulcers?

A. Supplemental vitamin A
B. Topical antibiotic ointment
C. Compression therapy
D. Hyperbaric therapy
• Answer: C
The cornerstone of treatment of venous ulcers is compression
therapy, although the best method to achieve it remains
controversial. Compression can be accomplished via rigid or
flexible means. The most commonly used method is the rigid,
zinc oxide–impregnated, nonelastic bandage. Others have
proposed a four-layered bandage approach as a more optimal
method of obtaining graduated compression. Wound care in
these patients focuses on maintaining a moist wound
environment, which can be achieved with hydrocolloids.
Other, more modern approaches include use of vasoactive
substances and growth factor application, as well as the use of
skin substitutes. Most venous ulcers can be healed with
perseverance and by addressing the venous hypertension.
Unfortunately, recurrences are frequent in spite of
preventative measures, largely because of patients’ lack of
compliance.
12. Which of the following is most
likely to cause a diabetic ulcer?

A. Uncontrolled hyperglycemia
B. Large vessel ischemia (peripheral
vascular disease)
C. Small vessel ischemia
D. Neuropathy
• Answer: D
It is estimated that 60 to 70% of diabetic ulcers are
due to neuropathy, 15 to 20% are due to ischemia,
and another 15 to 20% are due to a combination of
both. The neuropathy is both sensory and motor,
and is secondary to persistently elevated glucose
levels. The loss of sensory function allows
unrecognized injury to occur from ill-fitting shoes,
foreign bodies, or other trauma. The motor
neuropathy or Charcot foot leads to collapse or
dislocation of the interphalangeal or
metatarsophalangeal joints, causing pressure on
areas with little protection. There is also severe
micro and macrovascular circulatory impairment.
13. A teenage, African American girl
presents with large keloids on both
earlobes 12 months following ear
piercing. Which therapy should be added
to surgical debulking of the lesions?

A. None—surgical resection alone is


sufficient as the initial therapy
B. Intralesional corticosteroids
C. Pressure earrings
D. Radiation therapy
• Answer: B
Excision alone of keloids is subject to a high recurrence rate, ranging from 45 to 100%. There are fewer
recurrences when surgical excision is combined with other modalities such as intralesional corticosteroid
injection, topical application of silicone sheets, or the use of radiation or pressure. Surgery is recommended for
debulking large lesions or as second-line therapy when other modalities have failed. Silicone application is
relatively painless and should be maintained for 24 hours a day for about 3 months to prevent rebound
hypertrophy. It may be secured with tape or worn beneath a pressure garment. The mechanism of action is not
understood, but increased hydration of the skin, which decreases capillary activity, inflammation, hyperemia,
and collagen deposition, may be involved. Silicone is more effective than other occlusive dressings and is an
especially good treatment for children and others who cannot tolerate the pain involved in other modalities.
Intralesional corticosteroid injections decrease fibroblast proliferation, collagen and glycosaminoglycan
synthesis, the inflammatory process, and TGFβ levels. When used alone, however, there is a variable rate of
response and recurrence, therefore steroids are recommended as first-line treatment for keloids and second-
line treatment for HTSs if topical therapies have failed. Intralesional injections are more effective on younger
scars. They may soften, flatten, and give symptomatic relief to keloids, but they cannot make the lesions
disappear nor can they narrow wide HTSs. Success is enhanced when used in combination with surgical
excision. Serial injections every 2 to 3 weeks are required. Complications include skin atrophy,
hypopigmentation, telangiectasias, necrosis, and ulceration. Although radiation destroys fibroblasts, it has
variable, unreliable results and produces poor results with 10 to 100% recurrence when used alone. It is more
effective when combined with surgical excision. The timing, duration, and dosage for radiation therapy are still
controversial, but doses ranging from 1500 to 2000 rads appear effective. Given the risks of hyperpigmentation,
pruritus, erythema, paresthesias, pain, and possible secondary malignancies, radiation should be reserved for
adults with scars resistant to other modalities. Pressure aids collagen maturation, flattens scars, and improves
thinning and pliability. It reduces the number of cells in a given area, possibly by creating ischemia, which
decreases tissue metabolism and increases collagenase activity. External compression is used to treat HTSs,
especially after burns. Therapy must begin early, and a pressure between 24 and 30 mmHg must be achieved in
order to exceed capillary pressure, yet preserve peripheral blood circulation. Garments should be worn for 23 to
24 hours a day for up to 1 or more years to avoid rebound hypertrophy. Scars older than 6 to 12 months
respond poorly.
14. The risk of small bowel
obstruction in the first 10 years after
left colectomy is

A. 5%
B. 10%
C. 20%
D. 30%
• Answer: D
Intra-abdominal adhesions are the most common
cause (65 to 75%) of small bowel obstruction,
especially in the ileum. Operations in the lower
abdomen have a higher chance of producing small
bowel obstruction. After rectal surgery, left
colectomy, or total colectomy, there is an 11%
chance of developing small bowel obstruction
within 1 year, and this rate increases to 30% by 10
years.
15. Intra-abdominal adhesions can be
decreased after laparotomy by

A. Frequent irrigation to keep bowel


surfaces moist
B. Using antibiotic irrigation at the
completion of the case
C. Wrapping anastomoses in hyaluronic
acid sheets prior to closure
D. Using only monofilament sutures in
abdominal wound closure
• Answer: A
There are two major strategies for adhesion prevention or
reduction. Surgical trauma is minimized within the
peritoneum by careful tissue handling, avoiding desiccation
and ischemia, and spare use of cautery, laser, and retractors.
Fewer adhesions form with laparoscopic surgical techniques
due to reduced tissue trauma. The second major advance in
adhesion prevention has been the introduction of barrier
membranes and gels, which separate and create barriers
between damaged surfaces, allowing for adhesion-free
healing. Modified oxidized regenerated cellulose and
hyaluronic acid membranes or solutions have been shown to
reduce adhesions in gynecologic patients, and have been
investigated for their ability to prevent adhesion formation in
patients undergoing bowel surgery. Wrapping of the bowel
suture area or placement in the proximity of the anastomoses
with these substances is, however, contraindicated due to an
elevated risk of leak.
16. A healthy 20-year-old presents to the
emergency room with a large,
contaminated laceration that he received
during a touch football game. Which of
the following solutions should be used to
irrigate this wound?

A. Sterile water
B. Normal saline
C. Dilute iodine solution
D. Dakin’s solution
• Answer: B
Irrigation to visualize all areas of the wound and
remove foreign material is best accomplished with
normal saline (without additives). High-pressure
wound irrigation is more effective in achieving
complete debridement of foreign material and
nonviable tissues. Iodine, povidone-iodine,
hydrogen peroxide, and organically based
antibacterial preparations have all been shown to
impair wound healing due to injury to wound
neutrophils and macrophages, and thus should not
be used.
17. Once the wound described above has
been irrigated and debrided, which suture
should be used to close the subcutaneous
layer?

A. Biologic absorbable monofilament


(plain gut)
B. Synthetic absorbable monofilament
C. Absorbable braided
D. None of the above
• Answer: C
In general, the smallest suture required to hold the
various layers of the wound in approximation should be
selected in order to minimize suture-related
inflammation. Non absorbable or slowly absorbing
monofilament sutures are most suitable for
approximating deep fascial layers, particularly in the
abdominal wall. Subcutaneous tissues should be closed
with braided absorbable sutures, with care to avoid
placement of sutures in fat. Although traditional
teaching in wound closure has emphasized multiple-
layer closures, additional layers of suture closure are
associated with increased risk of wound infection,
especially when placed in fat. Drains may be placed in
areas at risk of forming fluid collections.
18. An alginate dressing is best used in
which of the following wounds?

A. An open traumatic wound


B. An open surgical wound
C. An infected wound
D. A partial thickness burn wound
• Answer: B
Alginates are derived from brown algae and contain
long chains of polysaccharides containing
mannuronic and glucuronic acid. The ratios of these
sugars vary with the species of algae used, as well as
the season of harvest. Processed as the calcium
form, alginates turn into soluble sodium alginate
through ion exchange in the presence of wound
exudates. The polymers gel, swell, and absorb a
great deal of fluid. Alginates are being used when
there is skin loss, in open surgical wounds with
medium exudation, and on full-thickness chronic
wounds.
19. Which of the following topical
agents has been shown to improve
healing in diabetic foot ulcers?

A. Epithelial growth factor


B. TGFβ
C. Platelet derived growth factor BB
D. Endothelial growth factor
• Answer: C
At present, only platelet-derived growth factor BB
(PDGF-BB) is currently approved by the Food and
Drug Administration for treatment of diabetic foot
ulcers. Application of recombinant human PDGF-BB
in a gel suspension to these wounds increases the
incidence of total healing and decreases healing
time. Several other growth factors have been tested
clinically and show some promise, but currently
none are approved for use. A great deal more needs
to be discovered about the concentration, temporal
release, and receptor cell population before growth
factor therapy is to make a consistent impact on
wound healing.

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