Tissue Injury and Repair: Wound Healing Flashcards Preview

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Flashcards in Tissue Injury and Repair: Wound Healing Deck (16):


network surrounding cells, dynamic

synthesized locally by mesenchymal cells

Dermis= ECM of skin

ECM is mechanical support for tissues, also a substrate for cell growth and formation of tissue microenvironments (sequesters iron and water)

regulates cell proliferation and differentiation

scaffolding for tissue renewal

storage and presentation of regulatory molecules (e.g. growht factors). 


Mesenchymal cells

connective tissue, muscle, blood, and lymphatics (basically anything not epithelial) 

cells linked to each other and to ECM


ECM examples

ECM= interstitium, interstitial matrix, stroma

synthesized by mesenchymal cells

collagens= fibrous proteins--> types 1, 2 and 3

water hydrated gels= proteoglycans and hyaluronan

Adhesive glycoproteins e.g. fibronectin 


Basement membrane

in skin: in between epidermi and dermis/epithelium and under-lying connective tissue

Beneath epithelium OR endothelium

synthesized by epithelium and underlying mesenchymal cells

Type IV collagen (nonfibrillar=lamina densa) and laminin

Can also be a site of pathology i.e. laminits 


equine hoof (epidermis): basement membrane

primary epidermal lamella and seconday epidermal lamellae

lamellae vastly increase surface area. weight of the animal is hanging off the basement membrane



inflammation is only part of the process. Laminitis is really a name of a set of clinical signs, not a disease

2 hypotheses: 1) vascular: digital ischemia and 2) toxic-metabolic: damage to epithelial cells or the laminae or to the BM

Acute laminitis: p3 separates from epidermal lamellae, leaving a cavity

Chronic: weight of the animal, the pulling power of the DDFT and a weakened structure of lamellae and BM, stretching and separation all lead to displacement of P3--> collapse of foot


What causes laminitis?

1. inflammation- inflammatory processes in the body can manifest as laminitis

a. retained fetal membranes b. severe illness, especially GI disease c. black walnut shavings d. feeding accidents e.g. grain overload

2. weight-bearing laminitis: if lame in contralateral leg, can compensante on other leg, get laminitis on non-lame leg (especially seen in forelimbs)

3. endocrine: a. glucocorticoids (equine cushing's, iatrogenic) b. insulin-resistance (pasture-associated laminitis, equine metabolic syndrome). 


How common is laminitis and what's the main cause?

in the UK, around 10% of horses in a single year will develop laminitis.

In the UK, the main cause is equine metabolic syndrome. Syndrome of obesity, laminitis and insulin resistance (hyperinsulinemia). It may be the high insulin that's a cause of laminitis rather than insulin resistance. 


Endocrinopathic laminitis vs. Inflammatory 

***Stretching of primary and secondary lamellae. No inflammation, just stretching.

Stretching of secondary epidermal lamella, cell death (apoptosis) followed by proliferation, BM lesions minimal. 


Inflammatory: separation of epithelial cells from BM, loss of BM

Lamellae tear: necrotic cells, inflammatory mediators, influx of small number of neutrophils. 


Connective tissue and repair

Connective tissue= tissue that supports, binds or separates other tissues or organs. Made up of mesenchymal cells and ECM

Repair by connective (fibrous) tissue necessary if:

-there's damage to the connective tissue (ECM+ mesenchymal cells) in addition to parenchymal cells or epithelial cells

-non-dividing cells are injured

In those circumstances, tissue can't be repaired by regeneration alone. Non-regenerated cells are replaced with fibrous tissue. 


Skin wounds

Mild superficial injury results in regeneration of epithelial cells and no scar

A deeper injury (i.e through the BM) results in the supporting connective tissue being damaged too, and that requires repair with connective tissue-->scar forms. 

Erosion: just epidermal damage

Ulcer: if injury goes through to ECM/connective tissue--> scar 


Liver injury

if we only injure hepatocytes, though not labile, can regenerate for the most part. if you injure any connective tissue--> scar tissue forms. 

End-stage liver= cirrhosis (injury to stroma and lots of hepatocytes)

results in macronodular or micronodular appearance

many intiating causes: toxic, infectious, genetic, biliary system disease, vascular disease. 


Four sqeuential and overlapping processes of repair

1. formation of new blood vessels- angiogenesis

2. migration and proliferation of fibroblasts

3. fibroblasts deposit ECM

4. maturation and reorganization of that fibrous tissue= remodeling 


Granulation tissue

tissue repair begins within 24 hours

granulation tissue forms by day 3-5


-fibroblast migration and proliferation into injury site

ECM deposition

named due to pink, soft, granular gross appearance (what you see beneath a scab)

Neovascularization: new vessels are leaky, so granulation tissue is often edematous. edema can persist long after acute inflammation has resolved.


What stimulates fibroblast migration and ECM deposition?

growth factors from 1) endothelial cells and 2) inflammatory cells

Macrophages are an important component of granulation tissue--> clear debris and fibrin; elaborate and numerous mediators. 

Granulation tissue progressively accumulates collagenous (extracellular) matrix. Acts as a scaffold for scar tissue formation. 


Scar formation

as healing progresses, decrease in number of proliferating (active) fibroblasts, decrease in blood vessels (vascular regression)--> pale appearance. Scar tissue has a LOT of collage (which is white).

Increased deposition of ECM ,especially collagen. Continues to be rmodelled- collagen synthesis and degradation by matrix metalloproteases.