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).
connective tissue, muscle, blood, and lymphatics (basically anything not epithelial)
cells linked to each other and to ECM
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
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.
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
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
tissue repair begins within 24 hours
granulation tissue forms by day 3-5
-fibroblast migration and proliferation into injury site
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.
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.