2 - Tissues Under Load

Question 1

What do I need to know?

Answer 1

1. How they are classified
2. Structure of collagens and PGs and how that structure underpins the mechanical properties of CTs
3. Know CTs are responsive to changes in mechanical forces
4. How the dermis of the skin is designed to withstand tension in multiple directions
5. Tendons/ligaments withstand tension and what happens when they are damaged and exposed to compression
6. How cartilage withstands compression and what happens when compressive forces are removed
7. How bone withstands pressure, tension, torsion

Question 2

What is the purpose of connective tissue?

Answer 2

Connective tissue provides mechanical support, a framework that enables the inflammatory response and so aids wound healing
The structure of CT predicts function and predicts the nature of the mechanical forces that act on the tissue
Many chronic diseases are of connective tissues

Question 3

What are 2 differences between CT and the other 3 primary tissues?

Answer 3

1. Nerve, muscle and epithelium (covers surfaces of other tissue) are CELLULAR tissues - large volume of cells with little space between them. CT has lots of ECM (98%) with a low volume of cells (2%) that are far apart
2. Properties of the cellular tissues depends on the properties of the CYTOPLASM or cell membrane (i.e. the cells)
   Properties of CT depend on the properties of the intercellular/extracellular materials

Question 4

Normally the tissue types have discrete functions but sometimes they overlap. Give 3 examples.

Answer 4

Some CT cells can contract (myofibroblasts)
Muscle cells can conduct an electrical impulse
Epithelial, nerve and muscle cells can all produce ECM

Question 5

What is connective tissue in the broadest sense?

Answer 5

CT is extracellular materials of fibres and cells embedded in a ground substance (soluble)

Question 6

What does CT locations reflect?

Answer 6

Their mesenchymal origin - they are INSIDE the body not surfaces (except joint cavity)

Question 7

What are the types of fibrous CT?

Answer 7

Loose - papillary layer of dermis, lamina propria
Dense > irregular; reticular layer of dermis
> regular; tendons, ligaments

Question 8

Types of cartilage?

Answer 8

Fibrocartilage - menisci, intervertebral discs
Elastic - kina of ear, epiglottis
Hyaline - articular

Question 9

Contents of CT?

Answer 9

Cells and extracellular matrix
-Cells = chondrocytes, osteocytes, fibroblasts (related and similar and change to each other depending on mechanical forces)

• Extracellular Materials
  1. Fibres > collagen, elastin
  2. Matrix > proteoglycans (glue)
  3. Glycoproteins > linking units
  4. Tissue Fluid
  5. Hydroxyapatite

Question 10

3 examples of glycoproteins

Answer 10

Fibronectin, osteonectin, laminin

Question 11

Examples of proteoglycans

Answer 11

Aggrecan, versecan, biglycan, decorin, hyaluronan (no proteo part)

Question 12

How can you predict what mechanical forces are acting on a tissue?

Answer 12

By the type, amounts and arrangements of the tissue composition/components. I.e. high collagen and PG = compression. High collagen low PG = tension

Question 13

What happens if CTs change environment?

Answer 13

CTs are responsive to the mechanical environment and will remodel if this changes. This means their classifications aren’t discrete but range of intermediate phenotypes i.e. compression at right angles to a tendon will change it to fibrocartilage

Question 14

What are the layers of the skin/cutis and briefly describe them?

Answer 14

Epidermis > 5 cellular layers
Papillary layer > hydrated
Reticular layer > 3D basket weave of collagen/elastin(lose with age)/fibroblasts that provides the most strength to skin when under load
Hypodermis/subcutaneous layer > adipose cells (insulation and padding)
Investing fascia > second skin of a sheet of collagen

The skin itself is the epidermis and dermis

Question 15

What are the 5 layers of the epidermis?

Answer 15

Stratum Corneum (shed)
Stratum Lucidum (clear)
Stratum Granulosum 
Stratum Spinosum
Stratum Germinativum 

Basal Lamina (not epi)

Question 16

What is between the epidermis and the dermis?

Answer 16

• basal lamina
• hemidesmosomes
• dermal ridges and dermal papillary pegs
• epidermal papillary pegs

Question 17

What are 4 epidermal derivatives and what are they useful for?

Answer 17

• hair, sweat glands, nails, sebaceous glands.

- source of epithelial cells for healing abrasions denuded of epithelium (NOT nails)

Question 18

Describe the structure of the reticular layer of the dermis and how it acts to resistent tension in the skin in 3 directions

Answer 18

• The WEAVE of fibres and cells in the reticular layer allows for initial stretch before resistance to tension meaning the skin can move around joints.
• The fibres have a preferred direction of alignment corresponding to the lines of skin tension (Langer’s Lines)
• Collagen itself is NOT extensible but as it is in a 3D TRELLIS-LIKE weave pattern, with tension this easily extends/straightens with little force (20%)
• Straight collagen fibres resist tension with increases load i.e. only 1-2% and then break

Question 19

Describe the structure of collagen and elastin

Answer 19

Collagen and elastin have cross-linked proteins.
Collagen is highly organised with a quasi-crystalline arrangement of the subunits (tropocollagen) that imparts resistance to tension
The elastic fibre subunits (tropoelastin) allow extension and recoil when subjected to and remove tension

Question 20

Describe the structure of tendons and ligaments

Answer 20

• closely packed parallel bundles of collagen fibres with intervening rows of compressed and elongated fibroblasts with a sparse capillary network
• few elastin fibres, more in ligaments
• low metabolic rate and capillary density to take long/hard to repair
• 1000s of parallel collagen fibrils in a fibre
• cells are called tenocytes

Question 21

What are flat tendons called?

Answer 21

Aponeurosis

Question 22

What allows tendons to slide with little friction?

Answer 22

Tendon sheaths - an inner epitendinium attached to the surface of the tendon and outer layer attached to the surrounding tissue. The space is filled with synovial fluid rich in hyaluronan

Question 23

How does the structure of tendons/ligaments relate to how they resist mechanical forces?

Answer 23

The collagen arrangement is already straightened so withstands tensional forces with immediate load input.
Resists tension with minimal elongation
Only stretch max 2% - this stretch is because the fibrils are relaxed when we aren’t using them
They need to be very resistent to tension in order to use muscles efficiently (they pull on bones)

Question 24

What happens to a tendon during a tetonomy (remove load)?

Answer 24

• the loss of tensional forces leads to rapid (1-2 weeks) remodelling
• rejoined tendons heal but slowly
• applying lateral pressure to a tendon results in remodelling into fibrocartilage
• goes from red staining to green 10 days post tenotomy showing it has gone from under tension to relaxed
• fibres become less aligned and parallel
• cells more rounded as the fibres have moved away and aren’t compressing them
• therefore the cells secrete more PGs which BIND water so tissue becomes softer and more hydrated

Question 25

What is a sesamoid?

Answer 25

A small bone/bony nodule developed in a tendon where it passes over an angular structure

Question 26

What do proteoglycans do?

Answer 26

Bind water and cause a tissue to become more hydrated

Question 27

What happens when you apply pressure to the side of a tendon - for example of flexor digitorum profundus?

Answer 27

- Proteoglycan levels increase in the pressure bearing regions (stains blue) and cells become rounded and look like chondrocytes - has become fibrocartilage with all intermediates seen - shows that cells respond to the gradient of mechanical forces

Question 28

What is the composition of a tissue under tension compared to one under pressure?

Answer 28

Tension: LOW PG (0.15% dry weight) being mostly decorin Pressure: High PG (2-4% dry weight) mostly aggrecan

Question 29

What happens after translocation of the tendon when there is removal of the pressure?

Answer 29

- leads to loss of PG after 10 days so it doesn't stain blue (fast) - this is not from adding tension just from removing pressure - when you put back the pressure you start to get back PG but slower and not to amount it was previously - the longer you remove mechanical forces the quicker the CT structure is lost and the harder it is to get back

Question 30

Describe hyaline distribution, growth and mechanical properties

Answer 30

- is widespread in fetus but restricted in the adult to ribs (costal cartilage allows us to flex when we breathe), joints etc. - interstitial AND appositional - resists compression due to proteoglycan aggregates - has high PG (10% dw) in load bearing region but less in periphery as we don't actually use the full range of motion in our joints. Use of our joint stimulates cartilage growth

Question 31

Describe the proteoglycan aggregate of cartilage (aggrecan aggregates on hyaluronan)

Answer 31

- chondroitin sulphate and keratin sulphate are glycosaminoglycans (GAGs)/repeating disaccharide units. They are negatively charged due to the sulphates and amino groups which DRAGS IN WATER - these accumulate onto a core protein to form a bottle brush/proteoglycan such as AGGRECAN - a link protein binds the protein core to hyaluronan - a GAG/2500 repeating disaccharide with NO protein and also drags in water - both the water and the negative charges resist compressive forces

Question 32

Describe hyaluronan and how does the mechanism work?

Answer 32

- a PG with no protein core and 2500 repeating disaccharide units - binds and drags water into tissues. Needs to be stimulated - the linking proteins to proteoglycans stops the molecules being dissociated during compression - There are fine collagen fibrils in the cartilage matrix. The carbohydrate/disaccharide chains of the proteoglycan drape over the collagen fibrils and the negative charges of the PGs bind to the positives on the collagen resulting in a stiff matrix that stays together during compression

Question 33

What is the relationship between PG and resistance to compression?

Answer 33

^ PG = ^ resistance. Measure the indentation at 2 seconds after the load is introduced - the 2 seconds creep modulus shows a linear relationship

Question 34

What happens when the compressive forces are removed from cartilage?

Answer 34

Not a lot happens to the structure as long as you keep MOVING the joint. Shows you don't have to load your joints to keep their cartilage and the joints healthy Seen in the sheep experiment Swing (no weight, moving) = nothing Straight (weight, no moving) = nothing Bent (no weight or moving) = 40% loss of PG in 4 weeks Shows passive movement or weight bearing alone maintains proteoglycan/structure in cartilage and so ability to withstand compressive forces (mechanical input needed is small)

Question 35

Discuss cartilage diseases

Answer 35

- cartilage has poor regenerative properties which result in chronic and long lasting problems that are difficult and hard to treat - E.G rheumatoid artritis; autoimmune disease of antibody mediated destruction of cartilage > inflammation - degenerative/osteoarthritis is universal in old age - due to increased mechanical stress to areas of articular surface with low PG such as the periphery

Question 36

What is fibrocartilage?

Answer 36

- fibrocartilage is designed to resist both tension and compression and is location restricted to menisci, annulus fibrosus, tendon insertions and sesamoid region of the fdp tendon in the rabbit around back of ankle where it is under pressure

Question 37

What is elastic cartilage?

Answer 37

Elastic fibres among type 2 collagen. Supports flexible structures

Question 38

What does bone resist and how?

Answer 38

Compression, tension (of acceleration) and torsion. Due ti collagen and mineral/crystal hydroxyapatite which resists pressure and torsion

Question 39

How is bone arranged?

Answer 39

- strength is due to arrangement of collagen fibres in sheets (lamellae) that alterate in fibre direction - lamellae can be concentric or flat (outer circumferential lamellae)

Question 40

Describe the types of bone

Answer 40

Adult (lamellar): Compact > incorporates a blood supple in haversian canals of osteons. Increases thickness with load Cancellous > web on thin pieces of lamellar bone (trabeculae) with bone occupying the spaces between Fetal (woven): Fine cancellous Also seen in a fracture callus, cartilage bone, membranc bone

Question 41

How are the osteons and trabeculae arranged?

Answer 41

- The osteons are arranged parallel to compressive forces passing down the shaft - Trabeculae are aligned with the directions of force and transfer the compressive forces from the head and center of the bone to the compact bone of the shaft (respond to the mechanical forces)

Question 42

Describe the lamellae organisation

Answer 42

Collagen fibrils in layers alternate in adjacent layers with each layer having most fibrils in same direction. Get increased strength for small amount of material