Physiological Steps of Wound Healing

February 6, 2013

Physiological Steps of Wound Healing

1.) Inflammatory Phase


  • Initial response to injury
  • Day 1-4 post injury
  • Characterized by rubor, tumor, dolor, calor
  • Platelet aggregation and activation
  • Leukocyte (PMNs, macrophages) migration, phagocytosis and mediator release
  • Venule dilation
  • Lymphatic blockade
  • Exudative
  • In wounds closed by primary intention, lasts 4 days
  • In wounds closed by secondary or tertiary intention, continues until epithelialization is complete

2.) Proliferative Phase

  • Day 4-42
  • Fibroblast proliferation stimulated by macrophage-released growth factors
  • Increased rate of collagen synthesis by fibroblasts
  • Granulation tissue and neovascularization
  • Gain in tensile strength

3.) Remodeling Phase

  • 6wks-1 year
  • Intermolecular cross-linking of collagen via vitamin C-dependent hydroxylation
  • Characterized by increase in tensile strength
  • Type III collagen replaced with type I
  • Scar flattens



"What Is Inflammation?

Inflammation is the body's attempt at self-protection; the aim being to remove harmful stimuli, including damaged cells, irritants, or pathogens - and begin the healing process. When something harmful or irritating affects a part of our body, there is a biological response to try to remove it, the signs and symptoms of inflammation, specifically acute inflammation, show that the body is trying to heal itself. Inflammation does not mean infection, even when an infection causes inflammation. Infection is caused by a bacterium, virus or fungus, while inflammation is the body's response to it.The word inflammation comes from the Latin "inflammo", meaning "I set alight, I ignite".
  Inflammation is part of the body's immune response. Initially, it is beneficial when, for example, your knee sustains a blow and tissues need care and protection. However, sometimes inflammation can cause further inflammation; it can become self-perpetuating. More inflammation is created in response to the existing inflammation.

According to Medilexicon's medical dictionary, Inflammation is:

"A fundamental pathologic process consisting of a dynamic complex of histologically apparent cytologic changes, cellular infiltration, and mediator release that occurs in the affected blood vessels and adjacent tissues in response to an injury or abnormal stimulation caused by a physical, chemical, or biologic agent, including the local reactions and resulting morphologic changes; the destruction or removal of the injurious material; and the responses that lead to repair and healing.

The so-called cardinal signs of inflammation are rubor, redness; calor, heat (or warmth); tumor, swelling; and dolor, pain; a fifth sign, functio laesa, inhibited or lost function, is sometimes added. All these signs may be observed in certain instances, but none is necessarily always present."

Inflammation helps wounds heal
Our immediate reaction to a swelling is to try to bring it down. Bearing in mind that inflammation is an essential part of the body's attempt to heal itself, patients and doctors need to be sure that the treatments to reduce swelling are absolutely necessary and to not undermine or slow down the healing process.

The first stage of inflammation is often called irritation, which then becomes inflammation - the immediate healing process. Inflammation is followed by suppuration (discharging of pus). Then there is the granulation stage, the formation in wounds of tiny, rounded masses of tissue during healing. Inflammation is part of a complex biological response to harmful stimuli. Without inflammation, infections and wounds would never heal.

Neuroscientists at the Lerner Research Institute at the Cleveland Clinic in Ohio found that inflammation actually helps to heal damaged muscle tissue. Their findings clash with how sportspeople with inflammation are treated - health professionals always try to control the inflammation to encourage healing. The researchers say their findings may lead to new therapies for acute muscle injuries caused by freeze damage, medications, chemicals and trauma.

Lan Zhou, M.D., Ph.D., said that patients should be very closely monitored when therapies to combat inflammation are used to make sure that the benefits of inflammation are not completely eliminated.

Inflammation is part of our innate immunity
Our innate immunity is what is naturally present in our bodies when we are born, and not the adaptive immunity we get after an infection or vaccination. Innate immunity is generally non-specific, while adaptive immunity is specific to one pathogen:

Whooping cough vaccine - example of immunity being specific to one pathogen
After being vaccinated for whooping cough (pertussis), we develop immunity to Bordetella pertussis or Bordetella parapertussis, types of bacteria that cause pertussis. This is an example of adaptive immunity - the immunity was not there before receiving the vaccine.
Inflammation is seen as a mechanism of innate immunity.

What is the difference between chronic inflammation and acute inflammation?
Acute inflammation - starts rapidly (rapid onset) and quickly becomes severe. Signs and symptoms are only present for a few days, but in some cases may persist for a few weeks. 

Examples of diseases, conditions, and situations which can result in acute inflammation include: acute bronchitis, infected ingrown toenail, sore throat from a cold or flu, a scratch/cut on the skin, exercise (especially intense training), acute appendicitis, acute dermatitis, acute tonsillitis, acute infective meningitis, acute sinusitis, or a blow.

Chronic inflammation - this means long-term inflammation, which can last for several months and even years. It can result from:

• Failure to eliminate whatever was causing an acute inflammation

• An autoimmune response to a self antigen - the immune system attacks healthy tissue, mistaking it (them) for harmful pathogens.

• A chronic irritant of low intensity that persists
Examples of diseases and conditions with chronic inflammation include: asthma, chronic peptic ulcer, tuberculosis, rheumatoid arthritis, chronic periodontitis, ulcerative colitis and Crohn's disease, chronic sinusitis, and chronic active hepatitis (there are many more).

Our infections, wounds and any damage to tissue would never health without inflammation - tissue would become more and more damaged and the body, or any organism, would eventually perish.

However, chronic inflammation can eventually cause several diseases and conditions, including some cancers, rheumatoid arthritis, atherosclerosis, periodontitis, and hay fever. Inflammation needs to be well regulated.

What happens during acute inflammation?
Within a few seconds or minutes after tissue is injured, acute inflammation starts to occur. The damage may be a physical one, or might be caused by an immune response.

Three main processes occur before and during acute inflammation:

• Arterioles, small branches of arteries that lead to capillaries that supply blood to the damaged region dilate, resulting in increased blood flow

• The capillaries become more permeable, so fluid and blood proteins can move into interstitial spaces (spaces between tissues).

• Neutrophils, and possibly some macrophages migrate out of the capillaries and venules (small veins that go from a capillary to a vein) and move into interstitial spaces. A neutrophil is a type of granulocyte (white blood cell), it is filled with tiny sacs which contain enzymes that digest microorganisms. Macrophages are also a type of white blood cells that ingests foreign material.Klaus Ley, M.D., a scientist at the La Jolla Institute for Allergy & Immunology, reported in a study published in Nature that neutrophils are the human body's first line of defense; they are the main cells that protect us from bacterial infections. Their protective function is a positive one, however, they also have inflammatory properties that may eventually lead to heart disease and several autoimmune diseases, such as lupus. Effectively manipulating neutrophils is vital in disrupting inflammatory diseases.

When our skin is scratched (and the skin is not broken), one may see a pale red line. Soon the area around that scratch goes red, this is because the arterioles have dilated and the capillaries have filled up with blood and become more permeable, allowing fluid and blood proteins to move into the space between tissues.

Edema - the area then swells as further fluid builds up in the interstitial spaces.

The five cardinal signs of acute inflammation - "PRISH"

• Pain - the inflamed area is likely to be painful, especially when touched. Chemicals that stimulate nerve endings are released, making the area much more sensitive.

• Redness - this is because the capillaries are filled up with more blood than usual

• Immobility - there may be some loss of function

• Swelling - caused by an accumulation of fluid

• Heat - as with the reason for the redness, more blood in the affected area makes it feel hot to the touch
The five classical signs of inflammation

These five acute inflammation signs are only relevant when the affected area is on or very close to the skin. When inflammation occurs deep inside the body, such as an internal organ, only some of the signs may be detectable. Some internal organs may not have sensory nerve endings nearby, so there is be no pain, as is the case with some types of pneumonia (acute inflammation of the lung). If the inflammation from pneumonia pushes against the parietal pleura (inner lining of the surface of the chest wall), then there is pain.

Acute and chronic inflammation compared
The lists below show the difference between chronic and acute inflammation regarding the causative agents, which major cells are involved, features regarding onset, duration, and outcomes:

Acute Inflammation

• Causative agents - harmful bacteria or injury to tissue

• Major cells involved - mainly neutrophils, basophils (in the inflammatory response), and eosinophils (response to parasites and worms), and mononuclear cells (macrophages, monocytes)

• Primary mediators - eicosanoids, vasoactive amines

• Onset (when does the inflammation start) - straight away

• Duration - short-lived, only a few days

• Outcomes - the inflammation either gets better (resolution), develops into an abscess, or becomes a chronic inflammation
Chronic inflammation

• Causative agent - non-degradable pathogens that cause persistent inflammation, infection with some types of viruses, persistent foreign bodies, overactive immune system reactions

• Major cells involved - Macrophages, lymphocytes, plasma cells (these three are mononuclear cells), and fibroblasts

• Primary mediators - reactive oxygen species, hydrolytic enzymes, IFN-γ and other cytokines, growth factors

• Duration - from several months to years

• Outcomes - the destruction of tissue, thickening and scarring of connective tissue (fibrosis), death of cells or tissues (necrosis)
Sleep quality and duration impacts on inflammation risk
Scientists at Emory University School of Medicine in Atlanta, Georgia, found in a study that sleep deprivation or poor sleep quality raise inflammation, which in turn increase the risk of developing heart disease and stroke.

The team gathered data on 525 middle-aged volunteers who had completed the Pittsburgh Sleep Quality Index (PSQI) questionnaire, which asked detailed questions about sleep quality and duration.

They tested the participants' levels of various inflammatory markers, and then tried to see whether they could link them to quality and duration of sleep. The authors concluded:

"The researchers concluded that: "Poor sleep quality, and short sleep durations are associated with higher levels of inflammation."

Why does inflammation cause pain?
What is pain? When people have inflammation it often hurts, they feel pain, stiffness, discomfort, distress and perhaps agony, depending on the severity of it. Pain can be constant and steady, in which case it is often referred to as an ache. Pain can be of a throbbing type, a pulsating pain, or it can be a stabbing or pinching pain.

Pain is a very individual experience and the only person who can describe it properly is the one who is feeling it.

Pain can be acute or chronic. It can also be:

• Nociceptive pain - specific receptors are stimulated for us to feel this type of pain. These receptors sense changes in temperature, vibration, stretch, and chemicals which damaged cells release. "Nociceptive" means causing or reacting to pain - the cause of the pain comes from outside the nervous system, and the nervous system reacts to it. "Non-nociceptive" means the pain comes from within the nervous system itself.

• Somatic pain - this is a kind of nociceptive pain. The sensation is felt in muscles, joints, bones, ligaments, and on the skin. Musculo-skeletal pain is somatic pain. Pain receptors are sentive to stretch in the muscles, vibration, temperature, as well as inflammation. When there is a lack of oxygen there may be painful ischemic muscle cramps.Somatic pain tends to be sharp and localized - touching or moving the affected area will result in more severe main.

• Visceral pain - this is a kind of nociceptive pain. Pain is sensed deep down in the body, in the internal organs and main body cavities, such as the heart, lungs, bowels, spleen, liver, kidneys, bladder, uterus, and ovaries. The nociceptors (pain receptors) sense oxygen starvation (ischemia), stretch, and inflammation. It is harder to localize visceral pain than somatic pain. The pain is usually described as a deep ache. Cramping and colicky sensations are examples of visceral pain.

Inflammation primarily causes pain because the swelling pushes against the sensitive nerve endings, which send pain signals to the brain. Nerve endings send pain signals to the brain all day long; however, it learns to ignore most of them, unless pressure against the nerve endings increases.

Other biochemical processes also occur during inflammation which affect how nerves behave, and cause pain.
Inflammation risk much greater if you are obese

Fat men have more inflammatory markers (white blood cells) than men of the same age who are not obese or overweight. Raised white blood cell levels are markers which are linked to a higher risk of developing various illnesses, including coronary heart disease.

In a recent study, a team from Pennington Biomedical Research Center in Baton Rouge, Louisiana, focused on specific types of white blood cells; neutrophils, lymphocytes, monocytes, basophils, and eosinophils.

They measured resting levels of the white blood cells in the adult males, as well as their levels of fitness and BMIs (body mass indexes), and adjusted the results for age. 

They found that:
• Unfit men had higher white blood cell levels that fit men

• Men with higher BMIs had raised levels of white blood cells

• The combination of fitness levels and body weights impacted considerably on levels of white blood cells, and ultimately inflammation
Although scientists know that inflammation plays a key role in heart disease and several other illnesses, what drives inflammation in the first place is still a mystery.

Inflammation drops when women lose weight - scientists at the Fred Hutchinson Cancer Research Center in Seattle, Washington found that postmenopausal overweight or obese women who lost 5% or more of their body weight had measurable falls in levels of inflammation markers. Team leader, Anne McTiernan, M.D., Ph.D., said "Both obesity and inflammation have been shown to be related to several types of cancer, and this study shows that if you reduce weight, you can reduce inflammation as well."

Autoimmune disorders and inflammation
An autoimmune disease, also known as autoimmune disorder, is one where the body initiates an immune response to healthy tissues, mistaking them for harmful pathogens or irritants. The immune response triggers an inflammatory response too.

There are literally hundreds of autoimmune diseases, and nearly all of them have inflammation as one of the signs, examples include:
• Rheumatoid arthritis - there is inflammation in the joins, tissues surrounding the joints, and sometimes some other organs in the body

• Ankylosing Spondylitis - there is inflammation of the vertebrae, muscles, ligaments, and also the sacroiliac joints (where the spine and hips meet)

• Celiac Disease - there is inflammation and destruction of the inner lining of the small intestine.

• Crohn's Disease - the gastrointestinal tract becomes inflamed. Inflammation is most common in the ileum (small intestine), but may occur anywhere in the GI tract, from the mouth to the anus.

• Fibromyalgia - often a set of symptoms related to another autoimmune disorder, such as lupus or rheumatoid arthritis. There is pain in various parts of the body. Location and even the existence of inflammation is unclear.

• Graves' Disease - one of the signs is goiter; when the thyroid gland is inflamed. Exophthalmos, inflammation of the muscles behind the eyes. Grave's dermopathy, inflammation of the skin, usually the shins and the top of feet (uncommon)

• Idiopathic Pulmonary Fibrosis - the role of inflammation is unclear. Experts used to think that the disease was mainly caused by inflammation within the alveoli (tiny sacs within the lungs). However, treatments to reduce inflammation are often disappointing. Therefore, although there is inflammation, its impact on the disease is a bit of a mystery.

• Lupus - there can be inflammation in the joints, lungs, heart, kidney and skin.

• Psoriasis - there is inflammation of the skin. In some cases, as in psoriatic arthritis, the joints and tissue surrounding the joints may also become inflamed.

• Type 1 Diabetes - inflammation in various parts of the body are likely if the diabetes is not well controlled.

• Addison's disease - inflammation of the adrenal glands. The stress to the body caused by this disease can also lead to inflammation elsewhere.

• Vaslculitis - refers to a group of disorders in which inflammation eventually destroys blood vessels, both arteries and veins.

• Transplant rejection - there is already substantial inflammation caused by the transplant operation. If the organ recipient's immune system rejects the new organ, there is typically inflammation in and around the donated organ.

• Various allergies - all allergies have inflammation. Asthma has inflammation of the airways, in hay fever the nose, ear and throat mucous membranes become inflamed, people who are allergic to bee stings may have serious life-threatening inflammation which affects the whole body (anaphylaxis).

• Vitamin A deficiency - inflammatory responses are much more likely if the person is deficient in vitamin A.
The disorders mentioned above are just a tiny example of the hundreds of autoimmune disorders which have inflammation as one of their signs.

More Info and References Here: "

Thanks to Anatomy in Motion for another great article.


Lysanne Lavigne RMT.

Prevent. Perform. Recover.

Equinox Health Clinic

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