16 September 2010

How the healing process really happens

Healing is a pretty fascinating process that our body is capable of producing all on its own in response to destroyed tissue. The process replaces lost tissue and restores structure, strength and function. It’s intertwined with inflammation and so there’s overlap between the responses as you’ll note after reading these posts and previous ones.
It all happens when tissue that is undamaged next to the damaged tissue begins to proliferate. Functional cells called parenchyma combine to form a stroma. Then, there’s two different ways healing takes place: regeneration or repair. Regeneration is when tissue is replaced. Repair is when fibrous car tissue is used to fill gaps.

Basically, reestablishing epithelium at damaged spots come with four components:

- Regeneration: This is when cells lost are replaced by mitosis by adjacent parenchymal cells. It’s ideal because new tissue is ideal for normal function.

- Repair: This is when fibrous connective tissue, or a scar (made of strong collagen) is used to restore structure, but can’t regenerate. Fibroblasts are up to the task of creating fibrosis since they tend to resist damage from injury.

- Revascularization: Despite whether or not regeneration or repair has happened at the site of injury, revascularization, or angiogenesis, restores blood supply. It is the process of production of new blood vessels coming to the site to supply nutrients.

- Surface restoration: When mitosis is happening at a site of injury, the new cells migrate to the edge and onto the surface where the injury is. They begin to organize secreting new basement membrane and when the edges meet, they become anchored in the membrane.

Primary healing is what we say to describe healing of a severing of a wound, or incision. There’s only minor damage with wound edges close to eachother. Bleeding narrows the gap, a clot forms, then a scab, an exudates and then a newly restored surface.

Secondary healing happens when wounds’ edges are not so close. They can happen commonly in skin and the GI tract (such as from a duodenal ulcer). The large wounds produce a lot more debris. The restoration process is extensive. Granulation tissue formation is needed to fill the wound gap, then there’s the aspect of wound contraction. The wound edges come closer toward the center through contraction that reduces the size of the gap. The contraction is caused by myofibroblasts, which are like modified fibroblasts that are derived from pericytes, which have the ability to contract.

Healing tissues

Connective tissue healing is prolonged because of a limited blood supply. Bone, or osseous tissue, has great regeneration abilities because of osteoblasts that are held in reserve, which work with osteoclasts to remodel bones. Tendons and ligaments can jusually recover from injury, but a bad injury can result in scar tissue or rough surface that causes weaker tensile strength or function. Cartilage heals by fibrous repair. Adipose tissue can’t go through mitosis, but precursor cells differentiate to produce new tissue.

Epithelial tissue can regenerate easily enough. They are frequently subject to injury. Regeneration will occur if epithelium damage is superficial. It can’t happen, however, if the basement membrane or intercellular matrix is disrupted, so in these cases fibroblasts will repair with scar tissue.

Glandular tissues are pretty stable and when injured they simply regenerate new tissue. For example, liver can regenerate very well. But if there’s serious damage, then there might be some functional loss.

Nervous tissue is made up of neurons that can’t go through mitosis, so if they’re damaged, then they’re replase by gliosis or proliferation of neuroglia. The neuroglia create a scarlike mass to block damaged axons to grow any further. Peripheral nervous system can replace myelinated neurons if Schwann cells stay undamaged.

Muscle tissues are permanent, so when damaged there is only fibrous repair causing loss of function. But muscles have compensation capabilities. The muscle cells increase in size and strength, called hypertrophy, which is what you get when lifting weights.

Healing problems

Sometimes healing doesn’t go so well. If the damage is too much, then collagen causes an exaggeration in wound contraction process called contracture. This can create distortion, such as seen in disfiguration after serious skin burns.

A second problem are adhesions, which result from inflamed exudates between serous membranes. These cause restriction in movement such as after surgery of heart or lungs, which sometimes require patients to be readmitted due to complications.

Dhiscence is when a healing wound breaks open because of pressure on the tissues. This happens most commonly in the abdominal wall because pressure interferes with formation of maturing collagen. It can lead to violent episodes of coughing, vomiting or diarrhea. A deficiency of vitamin C could also cause dehiscence problems.

Keloids are masses of scar tissue that are protruding through skin. They happen when dermal collagen is overproduced. Proud flesh is a problem of excess granulation tissue. Suture complications can result in cases when keratin is sealed within a suture tract.

Lastly, therapy sometimes can interfere with healting as in radiation or chemicals used in cancer. And anti-inflammatory or immunosuppresants can stop protein synthesis, wound contraction and regeneration.

Controlling healing

Healing is regulated closely, but not well understood. We know of two categories of chemical control factors including growth factors and growth inhibitors. As their names imply, they act in antagonistic ways promoting growth and stopping it. They are vital for migration of fibroblasts and epithelial cells, as well as formation of blood vessels, mitosis, and collagen formation.

Healing depends on cell interactions, especially in the extracellular matrix. Receptors on fibroblasts allow for binding elements of intercellular material. So, the matrix plays a role in regeneration and repair. The matrix interactions provide the regulartory input for healing as long as it is available undamaged.

Somehow, contact between cells physically regulates mitosis. In other words, cells undergoing mitosis stop once contact inhibition happens. You can see this in cells growing in laboratories. They start dividing and migrate, but when they meet they stop.

Worth noting is that growth factor therapy is being studied to better control healing in the future. Preparations of various growth factors could be used for therapy in several instances. Such as burn victims.


Nowak TJ, Hanfod AG. Pathophysiology: Concepts and applications for health care professionals, 3rd ed. 2004. New York, McGraw-Hill.

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