Tissue Injury and Repair: Connective Tissues

Question 1

Tendon structure

Answer 1

tendon is made up of crimps

crimps are made up of fascicles

fascicles are made up of collagen fibrils which follow a zigzag pattern; wave form in longitudinal orientation

each fibril is made up of stacked collagen- quarter stagger arrangment

each fascicle is roughly 1mm in diameter, hexagonal in cross section. Move past one another in tendon.

crimp lends faint, braided pattern

endotenon=fine bands of connective tissue between fascicles. not a very vascular tissue.

Question 2

tendon structure 2

Answer 2

there’s not always a synovial sheath around tendon

fetlock region: no paratenon—>from inside to outside: tendon, epitenon, synovial sheath, retinaculum

metacarpal region (canon bone): no sheath, there IS a paratenon–> from inside to outside: tendon, epitenon, no sheath, paratenon

endotenon- fine bands of connective tissue between fascicles that comes in from epitenon.

Question 3

Tenocytes

Answer 3

=fibroblasts of tendon

synthesize and degrade all of the collagenous and non-collagenous matrix.

Adult: 75% of dry mass is type I collagen and the rest is made up of proteoglycans, glycoproteins, water, etc

Tenocytes have long processes connecting each other–> control matrix as a network of cells.

Linked by gap junctions and adherens junctions into a network

Question 4

Superficial digital flexor tendon

Answer 4

injury: age is a risk factor; usually occurs spontaenously during exercise, frequently while training after competition

Previous accumulation of microdamage=subclinical

Question 5

Microdamage in the SDFT

Answer 5

Early: 1) ageing: decreased celluarity, increased percentage of type I tenocytes (and length) NB: type 1 are less active; decreased gap junction communication; decreased crimp angle > 10 years

2) exercise: decreased crimp angle <10 years; decreased collagen fibral diameter; decreased glycosaminoglycan content.

More advanced microdamage: red-core lesion: no clinical signs, no swelling, often found incidentally on PM, can be seen on U/S– more type III collagen fibrils=small, weaker fibrils.

Question 6

Why is SDFT prone to injury?

Answer 6

SDFT stores kinetic and potential energy as elastic energy= biological spring. nb suspensory does same type of thing.

Energy savings during a gallop= 36%–> muscles don’t have to work as hard. Muscle dampens high-frequency oscillations in the limb.

Energy storing tendongs have low mechanical saftey margins- must stretch tendon A LOT. At a gallop, SDFT is being stretched to the max.

At a gallop, get really high stretching/loading and high temperature (esp. centrally which is where we see the injury).

SDFT is loaded SLIGHTLY before other digital tendons/ligaments–> bearing all the weight for just a fraction of a second

Trotters–> suspensory ligament damage more frequent, as well as hind limb SDFT damage.

Question 7

Equine SDFT: the perfect storm

Answer 7

Susceptible population: few cells, inactive, linked together, ageing. Any cell death or dysfunction lends significant impact. The tendon cells may play an active role in that the cells start to change the tendon in a way that injures it further.

Causes: ageing, hypoxia (during exercise), overstress, stress-deprivation–> if some fibrils ruptue/not-stretching anymore, cells make enzymes to break down matrix; compression, hyperthermia

Nature of dysfunction? Type III collagen is more abundant, matrix metalloproteinases, inflammatory mediators.

When you reach maturity, collagen doesn’t turn over anymore

Initial injury doesn’t seem to be inflammatory but may end up with an inflammatory response.

Question 8

Clinical tendon injury

Answer 8

much longer time period than injury/recovery anywhere else.

clincal lesion (sub-acute- 3 weeks): enlargement, neovascularization, fibroplasia, inflammation

Chronic clinical lesion (>3 months)= still enlarged, thickened paratenon, scar tissue.

Question 9

Cells involved in tendon repair

Answer 9

Fibroblastic cells

-endotenon and epitenon (intrinsic repair)

extrinsic repair= tendon has no internal ability and requires adhesions and extra-tendonous blood supply

-tenocytes in peri-lesional tissue? Stem cells?

Dramatic hypertrophy of the endotenon by both vascular and fibroblastic elements- fascicles need to be able to move past one another, but that’s difficult with such an expanded endotenon.

Question 10

Major problems in tendon healing

Answer 10

Fascicles get stuck together and destroyed by scar tissue, not regenerated. Function of tendon is severely affected.

Scar tissue persists: increased type III collagen for 14 months or more. Ruptures can occur at margins of normal and scar tissue.

Inflammatory cells (and blood vessels) persist in endotenon- older horses may be less able to resolve this

For regions with overlying synovial sheaths, there may be a secondary synovitis.

Question 11

Articular Cartilage

Answer 11

white to blue, grossly

thickest in young animals and at sites of maximal weight bearing

at margins, merge with periosteal surface lined by fibrous tissue that’s contiguous with synovial membrane

No nerves, blood or lymphatic vessels

Nutrition= diffusion from synovia fluid and subchondral blood vessels.

Chondrocytes are NOT mitotically active and have poor regenerative capacity. Collagen is mainly type II

Question 12

Layers of cartilage

Answer 12

from outside to inside (closest to bone)

Superficial layers resist shearing forces (layers being shifted relative to one another)

Middle layers function in shock absorption

Tidemark=boundary between uncalcified articular cartilage and calcified cartilage. Calcified cartilage attaches articular cartilage to bone by its irregular (interlocking) interfaces.

Question 13

Cartilage injury

Answer 13

Any inflammation is due to synovium or bone inflammation

injury is non-painful unless subchondral bone or synovium is involved.

does NOT participate in inflammatory response– it’s affected by the inflammation in the synovium, subchondral bone, or growth cartilage.

Sterile injury= can be consequence of trauma, joint instability (ligament injury), lubrication failure (e.g. synovial pathology)

NB:cartilage resists neoplastic inflammation.

Question 14

Cartilage injury 2

Answer 14

as in tendon, repetitive stress can damage both the matrix and the chondrocytes, leading to inappropriate cellular responses (e.g. production of degradative enzymes), chondrocyte death, and therefore a vicious cycle of injury (i.e. accumualtion of micro damage)

Disruption of proteoglycans, collagen and proteoglycan-collagen interactions.

Limited response to injury and minimal capcity for repair

If proteoglycans are lost, collagen fibers condense and fray=fibrillation.

Clefts and fissures in the vertical axis (perpendicular to joint surface)

Fibrillation is accompanied by erosion. Erosion= hasn’t gone through full thickness of cartilage; ulceration=all the way throuh the cartilage.

Question 15

Cartilage ulceration

Answer 15

=full thickness loss

filled with vascular fibrous tissue- no replacement of cartilage

exposed subchondral bone develops increased density due to increased mechanical use= eburnation

Ulceration of cartilage–>bone loaded differently–> no shock absorption–> bone thickens and reacts–> eburnation.

Question 16

Degenerative Joint Disease

Answer 16

doesn’t imply a cause

Chondromalacia (softening of cartilage)–> erosion and fibrillation–> ulceration.

Often in DJD, get formation of peri-articular osteophytes=multiple bony outgrowths/spurs.

formation of periarticular osteophytes is initiated by mechanical instability of the joint and/or inflammatory cytokines.

Osteophytes don’t grow continuously, but persist once they’re formed.

Osteophytes can form within the joint cavity (perichondrium) or form periosteum at junction with joint capsule

Often secondary synovial inflammation and hyperplasia.

Question 17

Pannus

Answer 17

=fibro-vascular and inflammatory tissue that arises in synovium and spreads over the articular cartilage. macrophages and collagenases destroy the cartilage and the joint may be fused.

This occurs with chronic infectious synovitis or immune-mediated diseases e.g. rheumatoid arthritis

Synovium becomes severely inflamed, makes fibro-vascular reactive tissue. Tissue creeps across surface. Enzymes and macrophages destroy cartilage and pannus has gone through cartilage to the bone–> may fuse joint.

Question 18

Osteochondrosis

Answer 18

a disease of growth plate cartilage; a group of lesions in young animals

often bilaterally symmetrical

focal or multifocal failure of endochondral ossification

involves metaphyseal growth plate and articular epiphyseal complex.

Pathology in metaphysis: due to accumulation of viable hypertrophic chondrocytes

Pathology of AE complex: due to an area of necrosis of epiphyseal cartilage.

Basic lesion= growth cartilage fails to become mineralized and replaced by bone. not sure how these lesions arise, but some work suggests that a defect in the vascular supply to the growth cartilage is involved.