In this post, we’ll take a look at how healing occurs after common
types of damage in a variety of organs.
When a simple, cleanly incised wound occurs in the skin and
the edges are closely apposed (for example in a sutured wound) healing occurs
by First Intention. In this type of healing there is minimal soft tissue defect
to be filled and there is minimal tissue damage and blood as well as low
numbers of bacteria. As a result repair is rapid. Immediately after the cut,
clotted blood containing fibrin and blood cells fills the narrow incisional
space.
Within 24 hours of the incision, neutrophils begin to infiltrate
the margins of the cut and the surface epithelium proliferates in order to cover
the wound. After 72 hours, the neutrophils are replaced by macrophages and
granulation tissue begins to form. On Day 5 the incisional space has been
bridged by granulation tissue and collagen is covered by epithelium. The
collagen fibres become more abundant and also begin to bridge the incision. By this
time the basal layer of the epidermis will have bridged the incision and
differentiation would have started. At 7 days, the strength of the wound is 10%
of unwounded skin.
After 7-14 days, the
inflammatory components of healing have regressed and there is continued
accumulation of collagen and fibroblasts. A month after the injury, the scar is
made up of connective tissue covered by intact epidermis. The strength of the
wound increases gradually with time but never reaches that of the skin prior to
injury. The maximal strength is about 80% of unwounded skin.
The process of healing by secondary intention is pretty much
the same is in healing by first intention. The difference is mainly that in
healing by secondary intention a large tissue defect has to be filled. As a
result, this method of healing differs from primary intention in a few ways:
-
The large tissue defect may be filled with
debris, blood and bacteria which results in a more intense inflammatory reaction
which lasts longer.
-
There is more granulation tissue formation in
order to fill the defect.
-
There is more wound contraction due to the
presence of myofibroblasts.
The healing of mucosal surfaces is similar to that of skin.
However, the mucosa is very labile and so regeneration is often complete. Large
amounts of damage will cause the formation of a scar or incomplete
regeneration. The contraction of the scar can have serious consequences,
particularly in tubular organs (eg. the intestine where stenosis may occur).
Central nervous tissue has a limited ability to regenerate
and almost no ability to form fibrous tissue. Mature neurons are permanent
cells and so can’t regenerate. However, the neuroglia (they are the cells that support
and protect neurons and are like the connective tissue of the central nervous
system) are stable cells. Thus, when there is a non-lethal injury to the
central nervous system, the inflammatory cells, macrophages and astrocytes are
able to clean the area up little fibrosis occurs. As a result, the centre of the
injury remains a fluid-filled cavity.
Peripheral nerves may regenerate but this is only useful if
the ends of the axon are opposing.
Cardiac muscle cells are permanent and can’t regenerate. Any
damage to cardiac muscle is repaired by granulation tissue formation and
scarring. Smooth muscle and skeletal muscle are able to regenerate somewhat. If
the myofibre of the muscle cell is destroyed, it is replaced with fibrous
tissue or fat. However, damaged muscle can regenerate as long as the cell
membrane remains intact.
If the underlying extracellular matrix remains intact,
regeneration may occur. However, this is not the case in most injuries and this
results in scarring and the loss of original tissue architecture. In the lung, if type I pneumocytes are
destroyed, type II pneumocytes proliferate and line the alveoli (this is called
epithelialisation). As long as there’s no ongoing disruption of the ECM, these pneumocytes
can differentiate back into type I cells. In the kidneys, cortical tubular
epithelium is the most capable of regeneration but glomeruli aren’t able to regenerate.
The liver consists of a population of stable cells which are
capable of regeneration as long as the supporting stroma is not disrupted. However,
if the stroma is repeatedly or extensively disrupted, fibrosis can:
a) Compress hepatocytes
b)
Isolate hepatocytes from blood supply
c)
Isolate hepatocytes from biliary tract
All this leads to more hepatocyte death and more fibrosis.
The healing of bone follows the same basic process of
healing in skin. Immediately after injury, there is acute inflammation and the formation
of granulation tissue. Growth factors released in the developing granulation
tissue stimulate osteoprogenitor cells in the bone and soft tissue surrounding
the fracture. This prepares them for future bone remodelling and matrix
production.
After one week, granulation tissue weakly stabilises the
ends of the fractured bone (this is called a soft tissue callus). Over the next
few weeks immature bone and cartilage appear in the soft tissues surrounding
the injured bone. This stabilises the bone in an uncomplicated fracture but not
enough to allow it to bear weight. As the fractured ends are bridged by a bony
callus it becomes mineralised and this makes the bridging harder and capable of
bearing weight.
That’s all for now, see you next time :)
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