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Inflammation is said to resolve when no structural cells have been lost after the inflammatory process is complete and phagocytosis has cleaned up the area. When the tissue has been damaged during the inflammatory process or in other ways, but the body itself is still alive, the tissue will either regenerate or be repaired by fibrous tissue. If none of the latter is required, the word "resolution" is also appropriate. If any repair by fibrous tissue occurs, there will be a scar.
TYPES OF CELLS
• We rank cells according to their ability to regenerate: • Labile cells ("continuous replicators") are constantly replenishing their neighbors that have died or been shed. Examples include the epithelium of skin, mucous membranes, oviducts, ducts; urothelium; endometrium; seminiferous tubules; bone marrow; lymphoid tissue. • Probably these cells would "like to" proliferate all the time, but are stopped by "contact inhibition" by their neighbors. More about this arcane subject when we talk about cancer.... • Epidermis can regenerate from the skin adnexal structures (hair follicles, sebaceous glands, sweat glands), enabling full removal of epidermis as for a skin graft.
as well as fibroblasts. when they are healing).• Stable cells ("discontinuous replicators") can proliferate rapidly in response to need. . since nothing will restore their specialized structure. especially when required to replace lost neighbors. smooth muscle cells.e. provided a scaffolding of fibrous tissue is available (i. and chondroblasts. endothelial cells (cuboidal. a few of these cells can regenerate the organ. • Cartilage and tendon heal very poorly. osteoblasts. Otherwise. the collagen framework in an area has not been totally wrecked). and called "angioblasts". Smooth muscle cells regenerate poorly. These include all glandular parenchymal cells..
(Plasma cells and other mature products of marrow are post-mitotic too. and there are reserve cells that can replace a lost portion of a skeletal muscle fiber. Nerve cell processes have some ability to regenerate.) . neurons. but can be replenished.• Permanent cells ("non-replicators") cannot undergo mitosis or be replenished after birth. and cardiac (non-failing heart) and (maybe) skeletal muscle cells. These cells include glia.
the less its powers of regeneration. Liver regenerates.• The more specialized the tissue. ." This isn't true.
You've seen granulation tissue -. there is already evidence of connective tissue repair. fibronectin. and buds ("angioblasts") sprout from the damaged capillaries. Of course.it was moist. jelly-like stuff under the scab that you picked off too soon.REPAIR BY CONNECTIVE TISSUE • A few hours after injury. The fibroblasts lay down collagen and proteoglycans ("ground substance"). so healing wounds are edematous both grossly and microscopically. Fibroblasts become active and begin to proliferate. there are plenty of macrophages (to keep the new tissue clean) and mast cells. • The fibroblasts produce ground substance. large nucleoli. Of course. The new tissue is called granulation tissue ("immature scar". Typically. red.). and abundant basophilic cytoplasm. and type III collagen. etc. . and some acquire contractile elements as in smooth muscle ("myofibroblasts"). and the fibrin meshwork is said to be undergoing organization. the cells will show lots of euchromatin. • The young vessels are leaky. later they will produce type I collagen for the mature scar. both kinds of cells invade the fibrin meshwork created during the injury and inflammatory response.
you may call it an "inflammatory pseudotumor". • Especially where there has only been chronic inflammation. the fibroblasts revert to a resting mode. eventually there is sufficient collagen to fill the gap (type I replaces the type III originally laid down in the granulation tissue). most of the capillaries are reabsorbed.• You may run into granulation tissue that doesn't mature. . and finally the myofibroblasts contract. you can also see dense collagen production. which of course also counts as scar tissue. or whatever. • If everything goes well. depending on its location. This is done by fibroblasts on the instructions of macrophages.
GRANULATION TISSUES • This higher power view illustrates the classic appearance of granulation tissue. and plump fibroblast nuclei. prominent vessels. newly formed reparative tissue that will eventually form collagen and contract to form a fibrous scar. . Note the loose. edematous ground substance.
.HEALING BY PRIMARY INTENTION • • • • • • • • A well-approximated surgical wound is the ideal situation for wound healing. and collagen continues to accumulate. Timetable for "the best possible wound" (i. Epithelial cells are regenerating from the edges of the wound surface. 2 weeks: Fibroblasts continue to multiply. 24 hours: Polys have entered the fibrin meshwork. protected one with edges apposed. Since the edges are close together and held tight by sutures and fibrin. forms a meshwork. The meshwork also contains platelets. 3 days: The fibrin meshwork is extensively invaded by macrophages. The wound is still growing stronger. the healing is by primary union or first intention.e. and there is little necrosis and hopefully no infection. though it will never have the tensile strength of uninjured tissue (sorry). though it will not re-grow adnexal structures. Capillary involution and scar contraction is well underway. A thin layer of epithelial cells now covers the wound surface. Granulation tissue is appearing at the edges of the incisions. and stops the bleeding. and the red scar is turning white. etc. a clean.. and there is abundant collagen. in a well-nourished patient with good blood vessels): minutes: Fibrinogen from the severed vessels is activated via one or the other arms of the clotting cascade. 5 days: Granulation tissue fills the entire wound. 4 weeks: The overlying epidermis is now normal.
Arm. healing surgical incision Clinical presentation • This image demonstrates healing by first intention. which occurs in clean. uninfected wounds that have apposed edges .
There is a larger fibrin meshwork (a scab. it excites excessive fibroblastic activity. the edges of the scab loosen.). more inflammation. When re-epithelialization is complete. down suture tracks. more granulation tissue. rich in red cells -.) • When epidermis grows underneath some of the fibrin meshwork. • As surface epithelium grows into crevices (i.now brown because of methemoglobin). possibly infection. the scab falls off. and more spectacular wound contraction (up to 90-95% of the original surface area. This is why there's more scarring where the sutures were. etc. • Scarring by secondary intention always produces some deformity .e..HEALING BY SECONDARY INTENTION • Most wounds do not conform to the above ideal.
A whitish-greenish-yellow neutrophilic exudate represents an inflammatory response to bacterial invasion of the wound .. Note the red granular appearance of the granulation tissue.Clinical • presentation Wounds with a large tissue defect heal by secondary intention. healing by secondary intention .Hand.
as after a burn. or fibrosis-producing disease. the result may be a crippling contracture. The weave of collagen in the final scar (primary or secondary intention) is never the same as in the surrounding connective tissue. (You'll excise it. You'll see plenty of these.) • More intractable are keloids. • Sometimes the granulation tissue undergoes striking proliferation beyond the wound margins.DEFORMITY IN SCARRING BY SEC INTENTION HEALING • When the scar contracts TOO well. . This is called exuberant granulations by physicians and "proud flesh" by the public. (literally "crab claws") disfiguring scars with excessive collagen production. seen primarily in darkly-pigmented people. messy surgery.
. • Pigment in a wound is likely to stay in the macrophages.the familiar "epidermal inclusion cysts" ("sebaceous cysts". Hemosiderin may persist for years in a scar.mishaps • may occur. etc. especially if the person already has a high total-body iron burden. • Fragments of epidermis trapped in a healed wound may grow into spheres "with the skin-side inside" -.) • Attempts by severed sensory nerves to grow back into wounded tissue may produce painful "traumatic neuromas".
and recognize the names of the others ("epidermal growth factor". "Big Robbins" lists the seven growth factors that seem to direct the production of granulation tissue. "fibroblast growth factor". fibroblasts. and angioblasts.WHAT MAKES WOUND HEALING HAPPEN • As for inflammation. .) Angiogenesis remains rather mysterious. 1995). such medicines as natalizumab (α4 integrin antagonist that has been found to be useful in Crohn's disease and multiple sclerosis) will probably come into use soon. Now is a good time to read up on "integrins" in your biochemistry book. Material in "Big Robbins" on cell-cell and cell-matrix interactions are still experimental. You should recognize platelet-derived growth factor as a key to fibroblast activation and fibrogenesis. a couple of factors are known (Science 268: 567. Contact inhibition and crowding seem to put the brakes on the process. "transforming growth factors α and β". interleukin 1. • Fibrin itself seems to attract inflammatory cells. and TNF/cachectin. growth factors for wound healing are continually being discovered.
Wound infection interferes with timely wound healing. We do not know exactly how glucocorticoids interfere with wound healing. Some surgeons supplement some or all of these nutrients for their postoperative patients. they inhibit the migration of fibroblasts into fibrin meshworks. (For starters. as the bugs can cling to the surfaces and thus escape phagocytosis. Adequate nutrition is needed for good wound healing.) • • • . Protein is needed for collagen synthesis.FACTORS MODIFYING INFLAMMATION AND REPAIR • • Despite conventional wisdom. Several enzymes required for wound healing are zinc-based. others) in a wound are a tremendous aid to bacteria in causing infections. but the effect is potent. and vitamin C for hydroxylation of the proline and lysine in collagen. sutures. Inadequate blood supply greatly interferes with both inflammation and healing. age is not known to exert much effect on inflammation or wound healing. Foreign bodies (dirt.
• -ostomy: The surgeon cut something to make a mouth. • -pexy: The surgeon moved the organ to the right place. • -plasty: The surgeon changed the shape of an organ. If one organ is named. the mouth connected two organs. • -ectomy: The surgeon cut something out. If two organs are named. . • -desis: The surgeon made two things stick to one another.Here are some names for surgical operations! • -tomy: The surgeon cut something. • -rraphy: The surgeon sewed something up. the mouth opened to the outside of the patient.
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