Tissue Injury and Repair: Healing by 1st and 2nd intentions

Question 1

Granulation tissue gone wrong: “proud flesh”

Answer 1

frequent complication of limb wounds in horses (not body wounds, and not really in ponies)

most common non-neoplastic proliferative cutaneous lesion

continued low level of neutrophilc inflammation- grumbling, low level inflammation just continues making granulation tissue

protracted fibroblast proliferation

Question 2

Sarcoid= differential diagnosis for proud flesh

Answer 2

sarcoid can have same gross appearance as proud flesh but it’s seen in horses, mules and donkeys

Can be flat, verrucous (wart-like) or nodular

Non-productive (not making virus) infection of bovine papillomavirus

locally agressive, non-metastatic fibroblastic tumours

most common skin tumor of horses (most often age 3-6)

Question 3

Sarcoids continued

Answer 3

frequently develop in trasumatized areas or at sites of wounds 6-8 months after healing

most common on head, legs, ventral trunk and can be found singly or in groups.

if it’s NOT on a limb, sarcoid is likely your top ddx.

Sarcoids are often biphasic–> epiderminal hyperplasia with rete pegs and fibroblastic proliferation (rete pegs= long projections. if epidermis is ulcerated, it removes the diagnosis featur).

epidermis may be ulcerated

fibroblasts at dermal-epidermal junction are often perpendicular to the basement membrane (distinctive histo feature not seen in granulation tissue.

Up to 50% of sarcoids recur following removal.

Question 4

Cutaneous wound healing

Answer 4

involves both epithelial regeneration AND formation of connective tissue scar

illustrative of general principles of wound healing

Question 5

Three main overlapping phases of wound healing

Answer 5

1. inflammation: ideally gone by day 3
2. formation of granulation tissue (–> scar tissue): granulation tissue should start at 1st day and peak at day 2-3; at 10 days, suture out of clean surgical wound.
3. ECM deposition and remodeling

Larger wounds also CONTRACT during the healing process. wound contraction occurs up until a month if it’s a large non-surgical wound.

Question 6

Healing by 1st intention

Answer 6

=primary union

example: a clean, uninfected surgical incision closed with sutures. very few naturally occuring wounds heal by 1st intention.

only focal disruption of epithelial BM- only a few epithelial and connective tissue cells die

epithelial regeneration predominates over fibrosis- not a lot of scar tissue, if any.

Question 7

24 hours to 7 days of 1st intention healing

Answer 7

neutrophils migrate into fibrin clot, followed by macrophages

basal cells at cut edge of epidermis begin to show mitotic activity

epithelial cells start to migrate and proliferate across the dermis; deposit BM as they progress and meet in midline under a scab.

Epidermis is thickened (hyperplastic)

Fibroblasts migrate in, proliferate and start to produce collagen; blood vessels form–> granulation tissue.

Question 8

Early weeks of 1st intention healing

Answer 8

continued collagen accumulation, fibroblasts start to reduce in number

further decrease in leukocytes, decreased edema, and vascularity

blanching=increased collagen, vascular regression (looks white)

Sutures out at 10 days- epidermis should be intact

Few to no inflammatory cells (will be some inflammation around the sutures)

Question 9

Months to a year of 1st intention healing

Answer 9

scar= dense connective tissue, covered by essentially normal epidermis. gradually increases in strength

dermal appendages that were destroyed e..g hair follicles, are permanently lost.

Question 10

Healing by 2nd intention

Answer 10

tissue loss is more extensive

abscesses, ulceration, larger wounds

• more intense inflammation
• abundant development of granulation tissue
• wound contracts by action of myofibroblasts

ragged or dirty or infected wound: defect due to loss of epithelium and underlying tissue +/- infection –> more inflammation, more cell death.

Question 11

1-2 weeks healing by 2nd intention

Answer 11

phase of rapid proliferation of granulation tissue–> bigger scab, zone of hyperemia in ulcers

Question 12

Early weeks of 2nd intention healing

Answer 12

healing lesion: epithelial proliferation and repair (pink/red); maturing granulation tissue

Question 13

3-6 weeks of 2nd intention healing

Answer 13

granulation tissue maturation and wound contraction

epithelial proliferation across granulation tissue surface before gradually shedding scab.

granulation tissue begins to contract, pulling wound edges closer together

can get puckered appearance with granulation tissue pulling together

hyperemia

Large fibrous scar: pale depressed scar with puckering around caused by wound contraction

thin epidermis over scar; white; devoid of hair follicles

Question 14

Wound contraction

Answer 14

within 6 weeks, large defects should be reduced to 5-10% of original size

Ascribed to presence of myofibroblasts=modified fibroblasts exhibiting features of contractile smooth muscle cells.

Question 15

Corneal ulcers

Answer 15

mild persistent irriation= cutaneous metaplasia–> becomes skin

rapid and/or severe injury= ulceration

Mild corneal irritation: can see this with decreased tear production or eyelash growing down into eye

epithelial hyperplasia–> rete pegs down into stroma of cornea

hyperpigmentation

stromal scarring–> some BVs coming in

Question 16

Shallow corneal ulcers

Answer 16

too rapid or severe for metaplasia- necrosis; usually results in ulceration

immediate stromal oedema due to absorption from tear film

n’phils absorbed from tear film

epithelial cells flatten and slide across ulcer.

Question 17

deep corneal ulcers

Answer 17

edema, neutrophilic inflammation, neutrophil-mediated stromal lysis

in-growth of fibroblasts and blood vessels from limbus (edge of cornea) (granulation tissue)–> maximum speed of 1mm per day

epithelial regeneration following stromal re-building

very susceptible to opportunistic infection

granulation tissue mature to resemble normal stroma, but never replicates the very specific lamella structure.

corneal clarity is permanently impaired.

Question 18

Wound healing: horses v. ponies

Answer 18

Wounds of ponies heal favorably, lower cost of treatment. have faster and more intense inflammatory phase. in horses, inflammatory phase is weaker and persistent. in horses, a lower initial production of inflammatory mediators–> faulty wound healing process.

horses: formation of granulation tissue is excessively fast and persists due to unrelenting inflammatory response. more extensive scar formation because epithelialization is the primary method of wound closure.
ponies: greater contribution of wound contraction- not due to disparity in innate contractile capaciy of the fibroblasts. epithelisation contributes less, due to the rapid wound contraction

Question 19

What prevents or delays healing?

Answer 19

infection: prolonged inflamm. phase- single most important cause
nutrition: e.g. protein deficiency inhibits collagen synthesis

mechanical factors: local pressure, trauma or torsion–>wound may pull apart (dehiscense) e.g. fibrogranuloma d/t unrestricted joint movement

Anemia, blood supply, o2 tension: e.g. horse limbs, diabetes

Age and physical status

dehydration (poor perfusion)

wound fluids: e.g. pockets of blood or serum

inappropriate dressings: e.g. continued use of a debridement dressing during repair phase

foreign bodies

underlying neoplasia: squamous cell carcinoma often ulcerate and LOOK like a wound

volumte of tissue: this is critical. even in tissues compormised of labile and stable cells, extensive injury will result in incomplete regeneration, and at least partial loss of function

Tissues comprised of permanent cells: inevitably results in scarring–nb in brain, no fibrocytes, can’t form scar tissue

Location: e.g. inflammation around pleural, peritoneal, synovial cavities. extensive exudates can be digested and reabsorbed. larger accuumulations undergo organization i.e. granulation tissue grows into it and a scar forms. rupture pulmonary abscesses and adhesions can form to pleural wall.

Aberrations in what begins as normal healing: e.g. proud flesh in horses

Chronic inflamm conditions with persistent stimulation of fibrogenesis by immune reactions: rheumatoid arthritis, cirrhosis, pulomnary fibrosis

Question 20

Wound healing in reptiles

Answer 20

similar phases but tissue maturation is slow

sutures remain in for 4-6 weeks ( versus 10 days)

ecdysis (shedding of scales, cyclical, days to weeks)- activity of epidermis and dermis promotes healing

maintaining reptiles at upper end of their optimal environmental temperature range promotes healing

wounds oriented cranial to caudal heal more quickly than transverse wounds

open wounds e.g. lamp burns have relatively low incidence of secondary infection.