04/11/2014

Langerhans cells

LCs, 2%5% of epidermal cells, are a dendritic cell subset that originates
from bone marrow precursors and populates the epidermis. They are the
professional skin-specific APCs and ingest antigen locally in the skin. After
antigen uptake, LCs migrate to the draining lymph node, where they mature
to potent stimulators for antigen-specific T cells, expressing high levels of
major histocompatibility complex molecules. (a) Section of immunostained
skin shows Langerhans cells (yellow) abundant in hair follicles (F), where
many microorganisms live, and throughout the epidermis (E). Keratin of the
epidermis and follicles is stained green.
(b) Langerhans cells among the other epidermal cells.
(Reproduced, with permission, from Romani N et al. Acta Path Micro
Immunol Scandinavica. 2003;111:725.)
Pastian Lines - Pastia's lines are pink or red lines seen in the body
folds (especially elbows and axilla) during scarlet fever. Linear
hyperpigmentation may persist after the rash fades

http://pedsinreview.aappublications.org/content/27/5/189/F2.expansi
on
What is a wound?
It is a disruption or injury to the skin which may be caused by
trauma, surgical interventions, mechanical insult, systemic
diseases/disorders
Layers of the Skin

Wound Healing Types

PRIMARY INTENTION

-wound edges approximated and secured

-heal by epithelialization and connective tissue deposition
-usually heal quickly
-e.g. surgical sutures

SECONDARY INTENTION
-wound edges not approximated
healing occurs by formation of granulation tissue, epithelialization and
contraction of wound edges (scar tissue formation)
allowing wounds to heal without surgical closure
-e.g. leg ulcer left to heal by scar tissue formation

TERTIARY INTENTION (Delayed Primary Closure)

- surgical wound is left open for an extended period to minimize risk of
infection
-initially, wound is debrided then left open

-generally closed through surgical procedure

Three Phases of Wound Healing

Not mutually exclusive events, rather, they overlap

Hemostasis
0-3 hrs
Initiates the healing process
Epinephrine is released
Clotting and vasoconstriction to reduce blood loss at site of injury
Platelets aggregate, clot formation, hemorrhage arrested, limits
blood loss
Clot acts as a provisional matrix, provides space in which cells can
migrate
Platelets release growth factors and cytokines

Inflammatory Phase
Main goal is debride wound, hemostasis
Initial response after acute injury (0-5 days)
May be present for longer periods in chronic wounds
Characterized by:
Pain
Edema
Erythema
Warmth
Inflammatory cells (platelets, neutrophils and macrophages) enter
the wound
Phagocytosis is triggered removal of harmful pathogens and
celuular debris is initiated
Key nutrients: vitamin C, E, selenium, arginine, cysteine,
methionine

Neutrophils
- release cytokines which recruit fibroblast and epithelial cells
-kill bacteria
Macrophages
-Phagocytose and degrade foreign matter
-Release extracellular enzymes to degrade necrotic tissue
-Secrete growth factors and cytokines
-Promote angiogenesis
-Recruit fibroblasts
Proliferative Phase
Overlaps with inflammatory phase
Begins 3-5 days post injury and may continue up to 21 days
Fibroblasts enter the wound, synthesize and deposite
o Extra cellular matrix(ECM)
o Growth factors (cytokines, stored in platelets), e.g.
PlateletDerivedGF, EpidermalGF, KeratinocyteGF, FibroblastGF
o Angiogenic factors
Granulation tissue + ECM fills in the wound deficit
Angiogenesis forms new capillary growth

Re-epithelialization occurs and new epithelial tissue covers the

deficit
Myofibroblasts: contract the wound, pulling the edges together to
close the wound
Key nutrients: vitamin A, C, thiamine, pantothenic acid, zinc,
manganese

Implications:
granulation tissue formation is the goal of this phase
it is the active phase
maintain moist wound healing
topical agents and antiseptics are known to be harmful to healing
tissue
Maturation (remodeling) Phase
Can start as early as 7 days and may last up to 2 years
Fibroblasts leave the wound
Collagen fibers, fibronectin and proteoglycan rearranged and
redistibuted

Collagen is remodeled into a more organized matrix, degraded and

digested by other protease enzymes
Granulation tissue matures into a scar
The tensile strength of the newly formed scar increases
o potential strength is 70-80% of original tissue
Key nutrients: vitamin A, C, zinc, copper, manganese

Implications:
Still healing internally
Increases risk of re-injury in the early phases of remodeling
May be important to protect newly healed tissue from friction and
shear
SCAR FORMATION

10,000 collagen fibrils in one collagen fiber!

STALLED WOUNDS (CHRONIC WOUNDS)

Interrupted inflammation:

*MMP = matrix
degrading proteases

Lack of blood flow perfusion/oxygenation essential to repair

process (PAD, PVD, pressure, vasoconstiction, atherosclerosis,
hypotension, hypothermia, anemia, COPD). Collagen fibril
croslinking begins to fail as tissue oxygen pressure falls below 40
mmHg, O2 is required for hydroxylation of proline and lysine to
synthesize mature collagen.
Nutrition protein, magnesium, calcium, vitamin K are essential
for collagen synthesis and development of normal tensile strength
Infection prolongs inflammatory phase, delays collagen
synthesis and epithelialization. Infection stimulates prostaglandin
E2 and thromboxane, thrombosis and vasoconstriction, wound
hypoxia. Infected wound may not have classical signs of infection,
and may evade detection.
Medications chemotherapeutic agents and anti-inflammatory
medications compromise wound repair, antiseptics may be harmful
to granulation tissue/inflammatory activity (e.g. acetic acid,
betadine, sodium hypochlorite solution)
Stress may contribute to delayed wound healing, elevate
corticosteroid levels, compromise immune function
Aging diminished inflammatory response
Obesity tissue is poorly oxygenated and vascularized
Co-morbidities siabetes, vascular and cardiac disease
Immunosuppression can retard wound healing and increase
susceptibility to infection
Itch-scratch-itch cycle cause irritation, pain, break in skin,
infection

INFECTED WOUND

NECROTIC TISSUE

-prevents the wound from healing

-non-viable tissue
-debridement offers opportunity to return a wound to an inflammatory
state
ESCHAR
The presence of an eschar implies tissue necrosis, infarction, deep
burns, gangrene, or other ulcerating process. It is a circumscribed,
adherent, hard, black crust on the surface of the skin that is moist initially,
protein rich, and avascular.

ESCHAROTOMY

As edema fluid accumulates, ischemia may develop under any constricting

eschar of an extremity, neck, chest, or trunk if the full-thickness burn is
circumferential. Escharotomy incisions through the anesthetic eschar can
save life and limb and can be performed in the emergency department or
operating room.
Resources
http://www.woundcme.org/node/11006/course/11047/content
http://www.thewoundinstitute.com/ft/providers/accredited_courses.asp#inte
rmediate
http://www.thewoundinstitute.com/ft/providers/accredited_courses.asp
http://education.nhsinc.com/courselist.php#
http://www.nature.com/jid/journal/v127/n5/fig_tab/5700715f1.html
Fitzpatricks Dermatology