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Canadian Medical Alliance for the Preservation of the Lower Extremity

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How Do Wounds Heal?

We spend a lot of time talking about wounds on this
website.  We discuss who gets wounds and the factors
that precipitate them.  We discuss how wounds form. 
We discuss the statistics of wounds.  We discuss how to
treat them.  So it's appropriate to spend a little time
discussing how the body actually heals a wound.  

The wound healing process progresses through four stages: 

Hemostasis, Inflammation, Proliferation, and Maturation. 

 

Wounds typically progress through those stages in a complex, carefully-controlled, predictable manner.  However, wounds can get stuck in one phase, and even move backwards, depending upon the ability of the body to heal and the outside factors to which the body is exposed, such as pressure on the wound, exposure to bacteria, moisture balance, and so forth.

The first phase of wound healing begins when the wound is created and blood begins to leak out of the vessels, and often out of the body.  Our bodies consider a breach in the body's structure as an emergency, and the body rushes to block the drainage of blood flow by forming a clot.  Hence, this phase is commonly known as the Hemostasis Phase, with "Hemo-" derived from the Greek, meaning 'blood,' and 'stasis' meaning 'standing still,' referring to the initial clotting of the wound.

To accomplish the goal of stopping the loss of blood, within seconds of the injury,

several steps are followed.  First, the arteries constrict to decrease blood flow.  

Once the blood flow is diminished, the next step is for the body to seal the gap.

This is accomplished through platelets.  Platelets, so named because they look

like small plates (see the photo to the right), are small  cellular fragments that

float around in our blood, ever ready to patch a hole in the body. 

We have a lot of platelets.  One drop of blood contains tens of thousands of

platelets.  Each platelet travels in the bloodstream for a week to ten days.  If

it has not been used in that time, the body's liver and spleen remove it.  Each

day 200 billion new platelets must be replaced.

When there is an injury to our body, a blood vessel is torn, and platelets

begin to stick to the torn vessel.  This is accomplished because platelets

are chemically attracted to the collagen underneath the lining of the

blood vessels. 

The glue that makes the platelets stick is known as von Willebrand factor

(VWF), which is stored in the lining of the blood vessels and released into

the blood when the vessel is injured.

As the platelets begin to stick together in order to seal the hole in the injured

tissue, something known as platelet adhesion, their shape changes. Finger-like
projections develop in the platelet (see photo to the right) that reach out to
grab other platelets, strengthening the clot.  This is  known as platelet activation. 

The platelets release chemicals to

call in other cells that assist in the

damage control and repair process.

This is known as platelet secretion.

 

In the photo to the near right you

can see the platelets (stained fuchsia
in the photo) beginning to clump

together. 

Within a minute of the injury, the

body releases coagulants.  Small,

white filaments of an elastic protein

known as fibrin are laid down like a

mesh, (far right), transforming the

blood into a viscous, gelatinous

clump that forms the clot.    

 

 

 

 

 

 

With some ulcers, the wound extends through the skin, and the clotting occurs at the skin edge exposed to the outside world.  Below left we see a relatively new wound, with freshly clotted blood still evident.  Below right we see a chronic wound with dried callused tissue.  This wound once bled through the skin, but was clotted weeks earlier, leaving the black discoloration (from oxidized blood) we see here.  

 

 

 

 

 

 

But in many neuropathic wounds, the bleeding and clot-forming process begins beneath the outer skin, which may initially remain intact.  In this case, what is often visible is a darkened bruising beneath intact skin, often before any actual break in the skin is visible.  Examples of this are below. For most ulcers on the bottom of the foot, these will eventually ulcerate.  

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Once the bleeding is stabilized, the next phase of wound healing

begins, the Inflammation Phase


In this phase of wound healing, we need the blood to deliver

oxygen, repair cells, and chemical signals to direct healing. 

So the blood vessels open up (vasodilate) to deliver these

materials.  

The increase in blood flow causes fluid, proteins, and cells to

spill into the region.  Red blood cells, carrying oxygen, enter

the wound to aid the body in healing activity.  Also entering

the arena are white blood cells (WBCs). These cells enter the

area and kill and remove bacteria and damaged tissue.  

Read more about WBCs and our defenses against infection

here.

Accompanying this increase in blood flow are the cardinal

signs of inflammation--redness, heat, swelling, and pain. 

Note the example to the right.  The bleeding has been

arrested.  There is, however, redness surrounding the wound. 

However, these cardinal signs of inflammation may not be

pronounced, or even evident, in some diabetic patients who

cannot mount a normal wound response.  And redness, heat,

swelling and pain are also present in infection, so this must

be carefully differentiated.

The Inflammation Phase normally takes 2-4 days, but diabetes

can inhibit vasodilation, inhibit the aggregation and function

of proteins and white blood cells, and alter the viscosity of

blood, each of which may adversely affect healing.  In many

chronic, non-responsive wounds, the injury may remain in an

inflamed state for long periods of time.  Learn more about

how high blood sugar can slow wound healing here.

It is in the Proliferative Phase of wound healing where the

body really begins to repair the wound.  (Proliferate means

to grow.)  Dozens of types of proteins and hormones known

as growth factors and cytokines released by the cells initiate

this reparative phase of healing. 

New blood vessels grow into the injured site, a process

known as angiogenesis. 

Our bodies' cells begin to release extracellular matrix, (right),

a complex mesh of tissue that serves as a scaffold to help

hold our tissues together.  Much of the extracellular matrix

consists of a variety of specialized proteins that provide

strength and elasticity and promote cell growth, adhesion,

and migration.  There are several types of proteins that

make up the extracellular matrix, the most important

of which is collagen.  Collagen represents about one third

of the protein in our body. 

Within the framework provided by the extracellular

matrix, cells reproduce, filling the deficit of the wound

from the bottom up. 

But the wound also comes together from the edges. 
As the cells at the wound edges start to grow,  

specialized fibers known as myofibroblasts, 
present in the wound, and are able to
contract like small muscles.  They act
to pull the wound edges together. 
In the example on the near left, we
see a foot with no remaining toes. 
The ulcer in the midfoot had been
present for nine (!) years. 

On the far right, we see the foot
after wound care was initiated. 

The wound edges on the bottom
of the wound are contracting, and
the wound is beginning to heal. 

Closure of a wound is eventually achieved
once the wound has filled in enough, or the
wound edges have come together enough, skin
cells begin to grow over the wound.  This process
is known as epithelialization.  

After healing is complete, these repair cells die away in
an organized, orderly way (a process known as apoptosis).

This portion of the healing process typically takes 3 or 4 weeks, but can be significantly delayed in large ulcers.  These wounds may also be delayed with poor circulation, poor nutrition, and in diabetics with poor sugar control. With high sugar,  enzymes that normally break down damaged tissue may break down new, healthy tissue.  The reconstruction of tissue may become abnormally haphazard and disorganized.  Further, if the patient continues to walk and traumatize the wound, the fragile, repaired tissues can be pounded by body weight, and die. 

Clinically, we want to see at least 40% wound healing within a month.  Failure to progress in healing means a chronic wound is developing that may not heal in 3 months or more, so it is important to keep a proper moisture balance, debride necrotic
tissue and remove tissue that may be inhibiting repair, and protect the wound from reinjury through offloading.

Newly-repaired tissue is fragile and susceptible to new injury.  So, after the proliferation phase, the Maturation Phase begins.  In the maturation phase, the body reorganizes the wound repairs.  New, thinner, more organized collagen replaces the thick collagen initially deposited in the proliferative phase.  The fibers aligned along tension line and are crosslinked for strength.  This maturation process may begin as early as 3 weeks, and may continue for 1 or 2 years. 

To see the effect of sugar on wound healing, visit our page on the effect of glucose on wound healing.

To return to the top of the page, click on the leaf below.

"The world breaks everyone.  And afterward, some are strong in the broken places."

 

--Ernest Hemingway

  A Farewell to Arms

Platelets (stained fuchsia) and red blood cells (light purple) clumping together to form a clot.  Shutterstock image.
 

Fibrin (the white mesh) and red blood cells.  Image courtesy
of Kevin Mackenzie, University of Aberdeen, through 

https://wellcomecollection.org/works/kzuf6ej9

Scanning Electron Microscopic view of 3D Collagen Extracellular Matrix.  Image courtesy of Petropolis DB, Rodrigues JCF, Viana NB, Pontes B, Pereira CFA, Silva-Filho FC. 2014. Leishmania amazonensis promastigotes in 3D Collagen I culture: an in vitro physiological environment for the study of extracellular matrix and host cell interactions. PeerJ 2:e317 https://doi.org/10.7717/peerj.317

Photo above from a scanning electron microscope
was cropped from a photo provided courtesy of David Gregory & Debbie Marshall 

https://wellcomecollection.org/works/d4gftepm

Photo below from a scanning electron microscope was cropped from a photo provided courtesy of David Gregory & Debbie Marshall 

https://wellcomecollection.org/works/xyavsgxv

This page written by Dr. S A Schumacher
Podiatric Surgeon
Surrey, British Columbia  Canada

Unless otherwise indicated, all clinical photographs are owned and provided by Dr. S A Schumacher.  They may be reproduced for educational purposes with attribution to: Dr. S A Schumacher, Podiatric Surgeon, Surrey, BC Canada

and a link back to this website, www.CanadianMAPLE.org.

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