Week 2 PBL

1. Type 1 and type 2 collagen

Type I Collagen - More than 90% of organic mass of bone

- The major component of skin, tendons and ligaments
- Synthesized by fibroblast, by section of procollagen and convert into collagen.
- A component of type I collagen called the pro-α1 and pro-α2(I) chain is produced from the COL1A1 and COL1A2 gene.
- Type I collagen is composed of 2 pro-α1(I) chains (which are produced from the COL1A1 gene) and 1 pro-α2(I) chain.
- Collagen fibrils assemble further to form large, extremely strong collagen fibers that may be further bundled by linking coll agens and proteoglycans.
Type II - Present mostly in cartilage, vitreous humor, and connective tissue
Collagen - Rich in chondroitin surface and hyaluronic acid to enhance joint mobility
- Type II collagen gives cartilage its tensile strength and elasticity, thereby enabling it to support the joints.
- Large type II collagen fibrils form a network with embedded proteoglycans, glycoproteins, water, and soluble ions.
- Type II collagen is synthesized as a procollagen molecule with non-collagenous amino and carboxy extension peptides, by articular chondrocytes which
represent
the only living elements within hyaline cartilage.
- Occurs as fibrils but does not form fibers or bundles

2. Histology of normal particular cartilage

Distribution of the cartilage

Articular Cartilage:

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 Articular Cartilage:

Zones: (depending on chondrocytes arrangement & collagenous fibres)

• Tangential layer
o Chondrocytes: rather small, flattened parallel to surface
o Collagen fibres: very fine, run parallel to the surface of cartilage
o Lamina splendens exist at the top
• Transitional zone
o Chondrocytes: slightly larger, round, isogenous
o Collagen fibres: oblique
• Radial zone
o Chondrocytes: fairly large, forms radial columns, perpendicular to articular cartilage
o Collagen fibres: follows chondrocyte columns
• Calcified Cartilage layer
o Rests on the underlying cortex of bone
o Matrix is slightly darker than the other layers

3. Articular cartilage changes in OA

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 Aging decreases the ability of chondrocytes to maintain and restore articular cartilage and thereby increases the risk of degeneration of the articular cartilage surface.
Progressive degeneration of articular cartilage leads to joint pain and dysfunction that is clinically identified as osteoarthritis. Joints that are weight-bearing (knees, hips)
or heavily used (wrist, fingers) are most prone to cartilage degeneration. Fragments released by wear-and-tear to the articular cartilage trigger secretion of matrix
metalloproteinases (which acts on fibril-forming collagen) and other factors from macrophages in adjacent tissues, which exacerbate damage and cause pain and
inflammation within the joint.

Symptoms :
• Pain, and often widespread and may be referred in distant site. It exacerbates during activities but relieved by rest.
• Stiffness, become constant and progressive.
• Deformity
• Loss of function
• Crepitus, may be felt over the joint
• Local tenderness, in superficial joints fluid, synovial thickening, or osteophytes

4. Describe articular cartilage lubrication and healing.

Forms of lubrication
• Elastohydrodynamic
 main mechanism during dynamic joint function
 elastic deformation of articular surfaces
 thin films of lubricant separate the surfaces
 a fully congruent joint will not allow a fluid film to form
• Boundary (slippery surfaces)
 bearing surface is non-deformable
 lubricant only partially separates surfaces
 The load-bearing surface is largely nondeformable, and the lubricant only partially separates articular surfaces.
 superficial zone proteins have a role in this lubrication mechanism
• boosted (fluid entrapment)
 concentration of lubricating fluid in pools
 trapped by regions of bearing surfaces that are making contact
• hydrodynamic
 fluid separates surfaces when one surface is sliding on the other
• weeping
 fluid shifts out of articular cartilage in response to load
 surfaces separated by hydrostatic pressure

Healing

Cartilage is slow at repairing, because it lacks vascularity and lack of migration of cell (solid matrix).

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 Deep lacerations (through tidemark)
• Defects that penetrate through tidemark into subchondral may heal with fibrocartilage.
• fibrocartilage produced by undifferentiated marrow mesenchymal stem cells
• a healing response is initiated with hematoma, stem cell migration, and vascular ingrowth.
• This response produces type I collagen (from fibroblast) and resultant fibrocartilage rather than desired hyaline cartilage as produced by chondrocytes.
• This repair cartilage (fibres-like) has diminished resiliency, stiffness, poor wear characteristics, does not resemble normal structure.

Superficial laceration (not through tidemark)

• leads to chondrocytes proliferation
• no healing takes place because of avascular nature of cartilage and lack of inflammatory response necessary for healing

5. Explain the role of proteoglycans and collagen and the changes in cartilage with disease and aging

Proteoglycan provide compression strength to cartilage, and is located in the ECM, can be in 2 types : chondroitin sulfate and keratan sulfate. They hold the structure
with collagen fibril and control the movement of water in the ECM to hydrate the matrix.

However when aging, proteoglycan mass and size decreased, with decreased concentration of chondroitin sulfate and increased concentration of keratan sulfate, thus
the protein content increases, but the water content decreased, so it becomes dehydrated. Also, collagen cross-linking is also increased and resulting in loss of tensile
strength and stiffer.

6. Describe the anatomy of knee joint

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7. Explain the anatomy, physiology and biomechanics of the cruciate ligaments and menisci.

a. Cruciate Ligaments:
i. Anterior (ACL) → common injury
• Anatomy& Physiology
o Controls anterior movement of the tibia
o Inhibits extreme ranges of tibial rotation varus & valgus stresses
o With PCL: Controlling joint kinematics by guiding the instantaneous center of rotation of the knee
o Consists of 2 major bundles: Posterolateral & Anteromedial
o Origo: on the PM side of lateral femoral condyle
insertio: anterior intercondylar tibial eminence
o Muscles surrounding → knee stabilization during movement (ant: quadriceps, post: hamstring, lat: gluteus medius & tensor fascia lata,
med: hip adductors)
o Composed of type 1 collagen fibers
• Biomechanics:
o Greatest force transmitted through the AM bundle: 60 and 90 degrees of flexion.
o Greatest force for the PL bundle: at full extension.
o Hence, at greater flexion angle, AM higher in situ force than PL (Gabriel et al)
ii. Posterior (PCL)
• Anatomy&Physiology:
o Primary stabilizer of the knee
o Origo: intercondylar notch of the femur on the roof of the medial femoral condyle
o Insertio: central on the posterior aspect of the tibial plateau, on a depression between the tibial plateaus, extending 1cm below the articular
surface.
o Composed of a larger AL and smaller PM.
o Broader and stronger than ACL
o Prevent posterior translation of the tibia on the femur
o Prevent hyperextension and limit internal and valgus/varus rotation.
o Central axis controlling and imparting rotational stability to the kne
• Biomechanics:
o AL tightest at midarc of flexion
o PM tight in extension and deep flexion
b. Menisci
i. Anatomy&Physiology:
• Crescent-shaped fibrocartilaginous (semi lunar cartilages)
• Partly divides a joint cavity
• Found in knee, wrist, acromioclavicular, sternoclavicular, temporomandibular
• Knee:
o Lateral and Medial Meniscus → provide structural integrity to the knee when it undergoes tension and torsion
o Two pads of fibrocartilaginous tissue → disperse friction in the knee joint between tibia and femur
o Concave on top, flat on bottom, articulates with tibia
o Attached to fossa intercondylar tibialis
o Disperse the weight of the body
o Reduce friction during movement
ii. Biomechanics:
Contribute to load transmission, shock absorption, stability for femorotibial articulation, nutrition, joint lubrication, and proprioception.

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 • Contribute to load transmission, shock absorption, stability for femorotibial articulation, nutrition, joint lubrication, and proprioception.
• Also serves to decrease contact stresses & increase contact area and congruity of the knee

8. Describe fibrocartilage and menisci

Fibrocartilage described in number 2, menisci in number 7

9. Structure and function of ligaments and tendons

Hierarchical Ligament and Tendon Structure :

Ligaments

Structure :

 Contain fibroblast

 More proteoglycan matrix than tendon

 Less volume and organization of collagen fibrils

Function :

 Connects bone to bone

 Provide stability

 Prevent dislocation

Tendons

Structure :

 Contain collagen fibrils (Type I)

 Contain fibroblast

 Contain proteoglycan matrix

Function :

 Carry tensile forces from muscle to bone

 Carry compressive forces when wrapped around bone like a pulley

10. Understand the pathophysiology of OA

OA is classified as primary (idiopathic) or secondary due to injury, deformity, diseases

Process:
Normal joints have little friction with movement and do not wear out with typical use, overuse, or most trauma. Hyaline cartilage is avascular, aneural, and alymphatic. It
is 95% water and extracellular cartilage matrix and only 5% chondrocytes. Chondrocytes have the longest cell cycle in the body (similar to central nervous system and
muscle cells). Cartilage health and function depend on compression and release of weight bearing and use (ie, compression pumps fluid from the cartilage into the joint
space and into capillaries and venules, whereas release allows the cartilage to reexpand, hyperhydrate, and absorb necessary electrolytes and nutrients).

The trigger of OA is most often unknown, but OA sometimes begins with tissue damage from mechanical injury (eg, torn meniscus), transmission of inflammatory
mediators from the synovium into cartilage, or defects in cartilage metabolism. Obesity triggers some of these defects in cartilage metabolism, leading to cartilage matrix
damage and subchondral bone remodeling mediated by adipokines such as leptin and adipsin. The tissue damage stimulates chondrocytes to attempt repair, which
increases production of proteoglycans and collagen. However, efforts at repair also stimulate the enzymes that degrade cartilage, as well as inflammatory cytokines,
which are normally present in small amounts. Inflammatory mediators trigger an inflammatory cycle that further stimulates the chondrocytes and synovial lining cells,
eventually breaking down the cartilage. Chondrocytes undergo programmed cell death (apoptosis). Once cartilage is destroyed, exposed bone becomes eburnated and

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eventually breaking down the cartilage. Chondrocytes undergo programmed cell death (apoptosis). Once cartilage is destroyed, exposed bone becomes eburnated and
sclerotic.

All articular and some periarticular tissues can become involved in OA. Subchondral bone stiffens, then undergoes infarction, and develops subchondral cysts. Attempts
at bony repair cause subchondral sclerosis and osteophytes at the joint margins. The osteophytes seem to develop in an attempt to stabilize the joint. The synovium
becomes inflamed and thickened and produces synovial fluid with less viscosity and greater volume. Periarticular tendons and ligaments become stressed, resulting in
tendinitis and contractures. As the joint becomes less mobile, surrounding muscles thin and become less supportive. Menisci fissure and may fragment.

OA of the spine can, at the disk level, cause marked thickening and proliferation of the posterior longitudinal ligaments, which are posterior to the vertebral body but
anterior to the spinal cord. The result can be transverse bars that encroach on the anterior spinal cord. Hypertrophy and hyperplasia of the ligaments flava, which are
posterior to the spinal cord, often compress the posterior canal, causing lumbar spinal stenosis. In contrast, the anterior and posterior nerve roots, ganglia, and common
spinal nerve are relatively well protected in the intervertebral foramina, where they occupy only 25% of the available and well-cushioned space.

Stages:
Knee OA can be sub-divided into 5 grades:

Grade 0: This is the “normal” knee health

Grade 1: Very minor bone spur growth and is not experiencing any pain or discomfort.

Grade 2: This is the stage where people will experience symptoms for the first time. They will have pain after a long day of walking and will sense a greater stiffness in the
joint. It is a mild stage of the condition, but X-rays will already reveal greater bone spur growth. The cartilage will likely remain at a healthy size.

Grade 3: Moderate OA. Frequent pain during movement, joint stiffness will also be more present, especially after sitting for long periods and in the morning. The
cartilage between the bones shows obvious damage, and the space between the bones is getting smaller.

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 cartilage between the bones shows obvious damage, and the space between the bones is getting smaller.

Grade 4: This is the most severe stage of OA. The joint space between the bones will be dramatically reduced, the cartilage will almost be completely gone and the
synovial fluid will be decreased. This stage is normally associated with high levels pain and discomfort during walking or moving the joint.

11. Progresses OA:

i. In Articular Cartilage:
• Loss of proteoglycans from matrix → chondromalacia → loss of elastic resilience → decreases shock absorbing ability → collagen fibrils support
decreases → susceptible to friction of joint function → tangential surface layers shredding → deeper vertical layers split → consequent fissuring
and fibrillation

ii. In Central Area of Joint Surface:

• exposed to most friction → softened & fibrillated cartilage gradually abraded down to subchondral → reaches articulating surface → eburnation of
art. Surface (gradually smooth as polished ivory) → loss of art. Cartilage → narrowing of cartilage space

iii. In Peripheral Area of Joint Surface:

• cartilage hypertrophy & hyperplasia → thickened rim of cartilage around joint margin → chondrophyte formation → endochondral ossification →
osteophyte/ bony spur formation → become larger and stacked → restrict joint motion

iv. In Subchondral Bone:

• Central: max stress → eburnated → hypertrophy → sclerotic → more dense
• Peripheral: min stress → atrophy → rarefied, osteoporotic → less dense

v. In Subchondral Bone Marrow:

• Mucoid and Fibrinous degeneration → Cystic lesion formation → cyst and joint surface communicate through defects in fibrous tissue and synovial
membrane → increased vascularity → pain

vi. In Synovial Membrane:

• Abraded dead cartilage → floats in synovial membrane → hypertrophy & moderate synovial effusion → mucin content increases → Viscosity
increases

vii. In Fibrous Capsule:

• Greatly thickened and fibrotic → limiting joint motion

viii. In Surrounding muscles:

• Spasm response to pain
• Stronger muscles (flexor) contracture

11. Describe the appropriate management options for symptomatic OA

Nonpharmacologic:
i. Patient education (esp. around obesity, weight loading, etc.)
ii. Heat and cold
iii. Weight loss
iv. Exercise
v. Physical therapy
vi. Occupational therapy
vii. Unloading in certain joints

Pharmacologic:
i. Hand
• Topical capsaicin
• Topical NSAIDs (including trolamine salicylate)
• Tramadol → analgesic for patients with highly resistant pain
• Not recommended: intra-articular therapies / opioid analgesics
ii. Knee & Hip
• Acetaminophen
• Oral NSAIDs
• Topical NSAIDs (diclofenac) → suitable for 75 yrs above, don't use oral NSAIDs for 75 yrs above
• Tramadol
• Intra-articular corticosteroid
o Provide pain relief, have anti-inflammatory effect
o 4 to 6 weeks per injection
• Not recommended: Hyaluronic Acid Injections
iii. For patients with elevated risk of GI toxicity from NSAIDs:
• Proton-pump inhibitor
• Misoprostol
• Selective COX-2 inhibitor → celecoxib

Surgical:
i. Arthroscopy
ii. Osteotomy
iii. Arthroplasty
iv. Arthroscopy debridement
v. Fusion and Joint Lavage

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LO :
1. how stiffness of knee happens
Knee stiffness happened because the fibro capsule is thickening since the synovial fluid adds up, and pain caused by inflammation, thus it limits the mobility of the joint.

2. how to classify oa (sign symptoms, apa yang membedakan gangguan sendi krn aging, ato krn ada OA?)

In OA, the water content in joints are excess, thus it causes inflammation. In contrary, in the aging process the water content decreased, and it causes the joint
dehydrated and risky to brittleness and breaks.

3. radiographic examination ligament tear, OA (cari osteofit dll)

Other X-ray images are in WO pathology of OA

Body respond to grow the tissue so it responds by performing ossification of bones, however because the body is not capable of growing cartilage, it alters to growing of
hard bones, specifically bone spurs.

4. management of OA (surgical, non surgical therapy lifestyle, medikamentosa)

Done, wo no 11

5. how muscle strength control pain and deformity

High muscle strength can perform as stress absorber, by means it decreases the tension of weight-bearing or pressures that is applied to joint, by holding tight and lifting
the bones so it is not all fully sustained by articular cartilage

6. perbedaan OA, RA, GA dalam bentuk table (usia faktor risiko, dll) [yg simetris cm RA]

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7. anatomy membrii inferior (complete)

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8. jenis dan perbedaan cartilage

Done, wo no 2

9. mengapa lama kaku OA RA beda? (Baca pathophysiology OA)

In RA the stiffness are prolonged, since it takes time to remove chemicals inside the joint when moving at the first time in the morning, and it tends to be stagnant hemostasis, and not yet having a good circulatory.
While in OA, the stiffness only felt a while, and recovered faster since it is caused only by inflammation.

Chondrocytes supposed to be producing proteoglycans and type 2 collagen, but instead of type 2 collagen, chondrocytes produce type 1 collagen, which results decrease in articular cartilage elasticity, and starting to
fall off into fragments (joint mice) inside the synovial membrane and it worsens along with the time and become teared. Type A synovium cell (in synovial membrane) works together with the cytokines to remove
debris, however it also secretes proinflammatory cytokines and cause inflammation which causes pain at the synovial site, and called synovitis. The articular cartilage slowly eroding during the time until the bone
exposed and having friction into each other, and the body responses as hyperplasia to the bone, some develop osteophyte or eburnation ya.

10. penyebab nyeri pd OA

Inflammation at the joint space (explanation above), lokasi nyeri nya ada di joint line, since inflammation occurs at the lining of the synovial membrane in the joint.

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