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Flashcards in Tissue Injury and Repair 2 Deck (19):
1

EXTRACELLULAR MATRIX

A dynamic network surrounding cells.
Produced locally by mesenchymal cells
(Mesenchymal cell- any non-epithelial cell eg. connective tissue fibroblasts, muscle/blood/lymphatic vessel cells)

Cells are linked to each other and to the ECM.

In the skin, the ECM is DERMAL; it does not regenerate if injured. Scar tissue forms.

Functions:
Mechanical support for tissues.
Substrate for cell growth and formation of tissue microenvironments (sequesters ions and water)
Regulates cell proliferation and differentiation.
Provides scaffolding for tissue renewal.
Stores and presents regulatory molecules. eg. growth factors.

Much COLLAGEN- type I, II, III fibrillar proteins.
Also water hydrated gels- proteoglycans, hyaluronan.
Adhesive glycoproteins eg. fibronectin.

2

BASEMENT MEMBRANE

Beneath epithelium or endothelium.
Separates epidermis and dermis.
Synthesised by epithelium AND underlying mesenchymal cells
Comprised of type IV collagen- NONFIBRILLAR, and laminin. Hemidesmosomes are present.
Can be a site of pathology (eg. laminitis)

3

EQUINE HOOF

The epidermis is specialised, forming the horn of the hoof.
The epidermis and dermis interlock due to primary and secondary lamellae.
The basement membrane lies between these lamellae.
The weight of the animal hangs off the basement membrane and the interlocking epidermal and dermal lamellae.

4

LAMINITIS

Most important in horses and cattle.
Laminitis describes a set of clinical signs, including inflammation, not a disease.
2 hypotheses:
1. VASCULAR -> digital ischaemia
2. TOXIC METABOLIC- damage to epithelial cells or laminae or basement membrane due to toxins/metabolites.

5

CHRONIC LAMINITIS

Weight of animal on hoof, pulling power of DDFT and weakened structure of lamellae and basement membrane causing stretching and separation can lead to DISPLACEMENT OF DISTAL PHALANX -> COLLAPSE OF FOOT.
Very painful.
This leaves a cavity which may fill with tissue in very chronic cases.

6

WHAT CAUSES LAMINITIS?

Three main causes:
1. INFLAMMATORY
eg. retained foetal membranes, severe illness (especially GI), black walnut shavings (USA), feeding accidents (eg. grain overload).
Causes separation of cells and basement membrane.

2. WEIGHT BEARING
eg. if animal is lame in contralateral limb; it will be compensating with the other limb. Especially seen in dressage horses due to unnatural distribution of weight. Especially FORELIMB.

3. ENDOCRINE
-Glucocorticoids- equine Cushing's Syndrome, iatrogenic (steroid treatment side effect)
-Insulin resistance- pasture associated laminitis, equine metabolic syndrome
(Disturbed glucose/insulin regulation is common to both endocrine laminitis causes)
Stretch of lamellae leads to cell death

7

MAIN CAUSE OF LAMINITIS

Equine Metabolic Laminitis.
Insulin resistance predisposes the animal to laminitis.
It may be the high insulin that is the cause of laminitis, rather than the insulin resistance.

8

CONNECTIVE TISSUE

Supports, binds or separates other organs and tissues.
Made up of MESENCHYMAL CELLS and ECM.
Four broad categories:
1. Connective tissue
2. Epithelial
3. Muscular
4. Nervous.

9

REPAIR BY CONNECTIVE (FIBROUS) TISSUE

Is necessary if there is damage to the connective tissue (as well as the parenchymal or epithelial cells),
or if non dividing cells are injured.

In these circumstances, tissue cannot repair by regeneration alone.
Non regenerated cells are replaced with fibrous tissue.

Repair by CT is often a combination of repair with connective tissue AND regeneration.

10

EROSION

Skin wound, where only the epithelium is damaged.
Epithelial cells can regenerate, so there is no scar tissue formation or loss of function.

11

ULCER

Skin wound where the dermis is damaged as well- connective tissue is damaged as well, so repair by fibrous tissue is necessary.
Scar formation occurs.

12

LIVER INJURY

If only the cells (hepatocytes) are damaged, they can regenerate, leaving no scar.

If the cell and ECM are damaged, repair by fibrous tissue must occur. Scar formation.
This is the most common outcome of liver injury.

13

CIRRHOSIS

An end stage injured liver.
Macro- or micronodular- Hepatocytes form nodules as they try to regenerate.
Fibrous response seen in ducts and bridging lobules.
Many initiating causes- toxins, infections, genetic, biliary system disease, vascular causes.
The gross and histological appearance of the liver itself often does not indicate the cause.

14

REPAIR

Four sequential and OVERLAPPING processes.
1. Formation of new blood vessels (angiogenesis)
2. Migration and proliferation of fibroblasts.
3. ECM deposit by fibroblasts.
4. Maturation and reorganisation of fibrous tissue- Remodelling.

15

ANGIOGENESIS

Neovascularisation.
Occurs by one of two ways:
1. Progenitor cells leave bone marrow, enter blood stream then go on to form new vessels.
2. Capillary sprouting from existing vessels.

16

GRANULATION TISSUE

Tissue repair begins within 24 hours of injury.
Granulation tissue forms in 3-5 days.
-ANGIOGENESIS
-FIBROBLAST MIGRATION AND PROLIFERATION IN TO INJURY SITE
-ECM DEPOSITION

Named due to pink, soft, granular gross appearance.
Distinctive histologically- Blood vessels and fibroblasts run perpendicular to one another.

17

NEOVASCULARISATION

New vessels are leaky, so granulation tissue is often oedematous.
Oedema can persist for long after the acute inflammation has resolved.

18

WHAT STIMULATES FIBROBLAST MIGRATION AND ECM DEPOSITION?

Growth factors- activated endothelial cells, inflammatory cells.
MACROPHAGES are important components of granulation tissue- clear debris and fibrin, elaborate numerous mediators.

19

SCAR FORMATION

Granulation tissue progressively accumulates collagenous matrix.
This acts as a scaffold for scar tissue formation.
As scar formation progresses, vascular regression gives pale appearance.
Number of proliferating fibroblasts decreases- phenotype changes so those that are still active are depositing more collagen ECM.
Scar continues to be remodelled- collagen synthesis and degradation (matrix metalloproteinases)