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MEDSCI201 > Tissues under load > Flashcards

Tissues under load Flashcards

1
Q

Types of mechanical loads

A

Unloaded
Tension (up + down away force)
Compression (up + down in force)
Bending (tension + compression)
Shear (opposite forces on opposite sides)
Torsion (twisting)
Combined loading (torsion and compression)

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2
Q

Type 1 collagen

A

90% of all collagen - bone/ligaments/skin
Structural collagen against tension

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3
Q

Type II collagen

A

Collagen - fibre - structural
Cornea

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4
Q

Type III collagen

A

Reticular fibres
Muscle, arteries, skin
fibre - thin

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5
Q

Type IV collagen

A

Basement membrane of epithelia
mesh

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6
Q

Structural levels of collagen type I: collagen synthesis

A

Synthesis of pro-alpha chain containing Gly-X-Y repeats.

Self-assembly of three pro-alpha chains.

Procollagen triple helix formation followed by secretion into the ECM.

Cleavage of propeptide

Self-assembly into FIBRIL (see banding pattern in the EM)

Aggregation of collagen fibrils to form a collagen FIBRE

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7
Q

What is x and y in Gly-X-Y repeats?

A

gly- glycine
x- proline
y - hydroxyproline

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8
Q

Scurvy

A

Vit C deficiency
Essential for production of lysyl hydroxylase, the enzyme that catalyses the hydroxylation of proline and lysine. Absence of Vit C - collagen doesn’t formed its coiled structure. Most prominent in areas with high collagen turnover (periodontal ligament)

Symptoms include rotten teeth, bleeding from all mucous membranes and bowed legs

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9
Q

Vit C role in collagen synthesis

A

Helps with cleaving using enzymes and golgi modification

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10
Q

Osteogenesis Imperfecta

A

Genetic disease - mutation int two genes that encode collagen type I.

Symptoms include brittle bones, weak tendons (tendinosis), abnormal skin, teeth and healing

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11
Q

Stickler syndrome

A

Type I - autosomal dominant inherited mutations in the COL2A1 gene
Type II defective formation of collagen type II

Flattened facial appearance, nearsightedness, varying hearing loss, osteoarthritis, joint pain

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12
Q

Proteoglycans

A

a core protein + one or more covalently attached glycosaminoglycan (GAG) chain

Long linear polysaccharides
Negatively charged due to sulphate and uronic acid groups. Repeating disaccharide units including glucosamine

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13
Q

Multiple GAG chains

A

Aggrecan, versican, perlecan

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14
Q

Biglycan

A

Two chains

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15
Q

Decorin

A

One chain
- decorates collagen fibres - limiting fibre size

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16
Q

Hyaluronan

A

Only GAG that is not sulphated
Binds large amounts of water - important for tissue hydration, joint lubrication and diffusion of molecules

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17
Q

Aggrecan

A

Larger aggregating protein rich in chondroitin sulphate. It forms large aggregates by binding to HA via link protein. Highly negatively charged and is ‘water loving’ forming a stiff gel within cartilage and the intervertebral disc. Loss of aggrecan in the intervertebral disc with age results in less shock-absorbing capacity

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18
Q

ECM turnover

A

Replaced by enzymes/protease (collagenases). Some are broken by metalloproteases. Secreted in development

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19
Q

Types of Collagenases

A

MMP1 and MMP13

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20
Q

Types of Aggrecanases

A

ADAMTS-4 and ADAMTS -5

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21
Q

Bone composition

A

Water 25%
Mineral composition 60-70%
Collagen 5-10%

Resist compression

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22
Q

Compact bone

A

dense and solid
Same cells but organised in concentric lamellae around blood vessels = osteons

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23
Q

Spongy bone

A

Network of struts and plates - same cells, parallel lamellae

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24
Q

Micro-organization of bone

A

Lamellae are cylindrical and aligned parallel to the long axis of bone.

Collagen (type I) spiral along lamella providing resistance to tensile forces.

Crystalline structure provides resistance to compression.

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25
Q

Macro-organisation of bone

A

Distribution of forces
Strength of bone is dependent on:
Quality and amount of collagen (mainly type I)
Mineral content (hydroxyapatite)
Overall density

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26
Q

Where is compact bone found

A

Regions of high loads in the cortex and in the diaphysis

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27
Q

Spongy/ trabecular location

A

Region of low loads or where stresses come from several angles. Spongy bone helps distribute loads, making bone light and protects the marrow within. Strength is gain from the organisation of trabeculae

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28
Q

Effect of gravity

A

Bone loss in lower extremities and lumbar spine

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29
Q

Aging and osteoporosis

A

Lose mineral and bones become less dense. Bone resorption outpaces bone formation resulting in decreased bone mass. Density and quality of bone is reduced.

Increased osteoclast activity and reduced osteoblast activity. Loss of calcium from the body and hormonal changes post menopause

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30
Q

Preventing osteoporosis

A

Weight-bearing activity - subject bones to stress. Bone cells lay down more collagen and mineral salts in bone matrix. Makes bones stronger

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31
Q

Articular cartilage resist load

A

Experiences compression with low amounts of tension & shear at articular surface.

Articular cartilage is a specialised form of hyaline cartilage, found at end of bones within synovial joints

Transition from a gel-like pliable tissue into the hard, ossified bone, with an intermediate of calcified cartilage acting as a protective cushion

32
Q

What happens to the cartilage ECM when a load is removed?

A

The ECM begins to reabsorb water and return to its original shape and thickness.

33
Q

How does water reabsorption occur in the cartilage ECM during unloading?

A

Proteoglycans, such as aggrecan, attract water back into the ECM due to their high negative charge density.

34
Q

What is the role of the collagen network during the unloading of cartilage?

A

The collagen fibers help to restore the ECM’s original structure by providing tensile strength and preventing excessive deformation.

35
Q

How does the viscoelastic nature of cartilage affect the unloading process?

A

Due to its viscoelastic properties, cartilage gradually returns to its original shape and thickness over time after the removal of the load.

36
Q

Describe the recovery phase of cartilage ECM during unloading.

A

During the recovery phase, the interstitial fluid flows back into the cartilage, rehydrating the ECM and restoring its biomechanical properties.

37
Q

What changes occur in the proteoglycan network during unloading?

A

The proteoglycan network re-expands as water is reabsorbed, helping to restore the cartilage’s ability to resist compressive forces.

38
Q

How does unloading affect nutrient and waste transport in cartilage?

A

Unloading allows for the diffusion of nutrients and waste products through the rehydrated ECM, supporting chondrocyte metabolism and health.

39
Q

Exercise and Aging

A

Cartilage remodels itself following mechanical stimulation however, both too little and too much mechanical stimulation can have deleterious effects on the tissue health.

Age - cartilage becomes stiffer, collagen has slow turnover and new collaged is rarely replaced. We lose water and cartilage thins

40
Q

Under use/Immobilisation

A

Muscle wasting, bone thinning and loss of cartilage matrix due to lack of loading stimuli.

Patients put on continuous passive motion (CPM) machines to maintain joint function

41
Q

Excessive use

A

Site specific reduction in proteoglycan content in articular cartilage which can lead to early onset of osteoarthritis.

42
Q

Osteoarthritis

A

Affects all tissues of the joint. Presents as degeneration of articular cartilage. Low grade inflammation which is thought to contribute to ECM breakdown and viscous cycle begins.

Stiffness, joint swelling, reduced mobility. Joint replacement surgery or exercise needed

43
Q

Articular cartilage composition

A

70-85% water
10-20% collagen - Type II
5-10% proteoglycans
5% chondrocytes

Aneural and avascular

44
Q

Zones within articular cartilage

A
45
Q

Superficial (Tangential) Zone:

A

Location: The outermost layer, closest to the joint cavity.

Characteristics: Contains flattened chondrocytes and a high concentration of collagen fibers arranged parallel to the surface.

Function: Provides a smooth, low-friction surface and resists shear forces.

46
Q

Middle (Transitional) Zone:

A

Location: Below the superficial zone.

Characteristics: Contains round chondrocytes and collagen fibers arranged obliquely.

Function: Acts as a transition between the superficial and deeper zones, absorbing compressive forces.

47
Q

Deep (Radial) Zone:

A

Location: Beneath the middle zone.

Characteristics: Contains larger, columnar chondrocytes aligned perpendicular to the surface, and collagen fibers are arranged in a radial orientation.

Function: Provides the greatest resistance to compressive forces and contributes to the overall thickness of the cartilage.

48
Q

Calcified Zone:

A

Location: The deepest layer, adjacent to the subchondral bone.

Characteristics: Contains hypertrophic chondrocytes and is characterized by the presence of calcified cartilage matrix.

Function: Anchors the articular cartilage to the subchondral bone, providing stability and distributing loads to the underlying bone.

49
Q

How OA progresses

A

Fibrillations - fraying of collagen

Collagen beneath SZ start to breakdown -> Free PG bring in H2O by bringing in more cations, increasing art cart height

Fissures develop - chondrocytes divide for futile repair and increase matrix prodution

Inflammation occurs - increased collagenase 1 and aggreanase which breaks down matrix

Bone is stiff, has pain and effusion with swelling

50
Q

Do supplements work

A

No, not really

51
Q

Why do we need tissue engineering

A

For articular cartilage and non-union fracture where gap between the two ends doesn’t bone

52
Q

Type of engineered tissues

A

Mechanical replacement
Cartilage
Blood vessels
Bone
Bladder
Skin

Biochemical replacement
Liver cells
Pancreas cells
Stem cells

53
Q

Making tissue in 3D

A

TE technique = cells + biocompatible scaffold

54
Q

Sources of cells

A

Autologous - from the person who is having the replacement

Allogenic - donor from the same species

Xenogenic - From a different species

55
Q

Scaffolds

A

Cells are placed in an artificial matrix forming a 3D structure
1. Allow cells to attach
2. Allow nutrient/waste delivery
3. Can apply mechanical loads

56
Q

Types of scaffolds

A

Collagens
Alginate gels

57
Q

Scaffold must be..

A

Biodegradable or biocompatible
Provide support for the initial growth phase
Moulded into any shape

58
Q

Autologous Chondrocyte Implant

A
  1. Biopsy
  2. Culturing of chondrocytes
  3. Inject of cultured chondrocytes and periosteal graft sutured over lesion
  4. The cells are implanted under the graft

Produces fibrocartilage NOT articular cartilage

59
Q

Complex synovial joint - the knee

A

Intra-articulating disc or meniscus

60
Q

Bones of the knee joint

A

Femur , tibia and patella. The fibula is not considered part of the knee joint.

61
Q

3 articulating surfaces within the knee joint

A

Between condyles of tibia and femur (later and medial tibio-femoral joints) Third is between the paella and the femur (patellar-femoral joint) on the anterior aspect of the joint.

62
Q

Knee flexion and extension

A

Movement in the sagittal plane
Adaptation of the lower limbs bones permit 140* of flexion.

63
Q

What restricts sliding of the knee

A

Intercondylar fossa & eminence restrict sliding

64
Q

Knee abduction and adduction

A

Not permitted by collateral ligaments

65
Q

Supporting ligaments

A

Connect bones and supporting viscera. Distribute tensile loads and control limit of joint motion.

66
Q

Extracapsular ligament

A

Ligaments that occur outside the articular capsule

67
Q

Capsular ligaments

A

Form part of the outer fibrous layer of the articular capsule

68
Q

Tibial (or Medial) collateral ligament

A

Reinforces medial surface of knee joint by joining the femur to the tibia

69
Q

Fibular (or Lateral) Collateral ligament

A

Reinforces the lateral surface of the knee by joining the femur to the fibula/tibia

70
Q

Intracapsular ligaments

A

Found inside the articular capsule (intercondylar fossa). Covered with synovial membrane that is continuous from lining of the articular capsule. Are the CRUCIATE ligaments

71
Q

ACL

A

Prevents forward gliding of the tibia in relation to the femur. Role in preventing knee from hyperextending

Past 30% hyperextension = rupture ACL

72
Q

PCL

A

Ligament prevents backward gliding of the tibia in relation to the femur

73
Q

Tendons of the knee

A

Are attached to muscle, placed under tension. Active stabilisation of the knee by the muscles and their tendons can help protect the knee when the ligaments are loose.

74
Q

Extensor muscles of the knee

A

Quadriceps femoris: consists of 4 muscles sharing insertion into tibial tuberosity via patella and retinaculae.

Most superficial is rectus femoris with 3 vastus muscles below

75
Q

Flexor muscles of the knee

A

Hamstring muscles: Three muscles with the semimembranosus and semitendinosus inserting inserting into the medial side of the tibia, while bicep femoris inserts on the lateral side of the tibia and head of fibula

MEDSCI201 (21 decks)

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