Week 1 PBL 1

1. Describe type 1 and 2 collagen: structure, function, and synthesis. (type 1  resistant tension; type 2 
intermittent pressure)
Type 1 collagen is found in bones, cartilage, tendons and skin. It accounts for more than 90% of organic mass of
bone and is also the major component of skin, tendons and ligaments. Type 1 collagen is a secreted extracellular
matrix protein. Proteins in these types include glycine, proline, alanine, and hydroxyproline.

One alpha 2 chain pairs with two alpha 1 chain to form the triple helix of type 1 collagen.
Function: As a structural protein, type I collagen interacts with other matrix proteins including proteoglycans and
fibronectin. By binding to the cell surface integrins alpha-1 / beta-1 and alpha-2 / beta-1 type I collagen can anchor
cells into the matrix. In addition to its structural roles, type I collagen signaling to cells through its integrin receptors
and other cell surface collagen receptors (CD36, inhibitory leukocyte-associated Ig-like receptor (LAIR)-1 (CD305),
Endo180 (CD280), and discoidin domain receptors, DDR1 and DDR2) can regulate cell growth, motility, and
differentiation.

The process of type I collagen synthesis. (a) Two identical α1(I) and one α2(I) peptide chains self-assemble to form
procollagen (b). (c) Procollagen peptidase removes loose termini to create a type I tropocollagen molecule (d).
Tropocollagen molecules self-assemble to form a growing collagen fibril (e). Self-assembly of collagen fibrils forms a
type I collagen fiber (f).
Type 2 collagen is the main collagen of cartilage and joints (fluid). This type is produced by chondrocytes (the non-
cellular matrix of cartilage). The fibril-forming type II collagen is the characteristic and predominant component of
hyaline cartilage. It is, however, not specifically restricted to cartilage where it accounts for about 80% of the total
collagen content since it is also found in the vitreous body, the corneal epithelium, the notochord, the nucleus
pulposus of intervertebral discs, and embryonic epithelial –mesenchymal transitions. The triple helix of type II
collagen is composed of three a1(II)-chains forming a homotrimeric molecule similar in size and biomechanical
properties to that of type I collagen. Compared to type I collagen, type II collagen chains show a higher content of
 hydroxylysine as well as glucosyl and galactosyl residues which mediate the interaction with proteoglycans, another
typical component of the highly hydrated matrix of hyaline cartilage.
2. Describe the histology of normal articular cartilage. (avascular)

Tangential layer
Chondrocytes are rather small and flattened parallel to the surface. The most superficial part (lamina splendens) is
devoid of cells. Collagen fibres in the matrix of the tangential layer are very fine. They run parallel to the surface of the
cartilage.
Similar to the collagen fibres of the skin, the general orientation of collagen fibres in articular cartilage is determined by
tensile and compressive forces at the articulating surfaces.
Transitional zone
The chondrocytes are slightly larger, are round and occur both singly and in isogenous groups. Collagen fibres take an
oblique course through the matrix of the transitional zone.
Radial zone
Fairly large chondrocytes form radial columns, i.e. the stacks of cells are oriented perpendicular to the articulating
surface. The course of the collagen fibres follows the orientation of the chondrocyte columns.
Calcified cartilage layer
It rests on the underlying cortex of the bone. The matrix of the calcified cartilage layer stains slightly darker (H&E) than
the matrix of the other layers.
The main source of nourishment for articular cartilage is the synovial fluid, which fills the joint cavity. Additional small
amounts of nutrients are derived from blood vessels that course through the calcified cartilage close to the bone.
Living chondrocytes have been found in small pieces of cartilage floating in the joint cavity after damage to the articular
cartilage.
3. Describe the articular cartilage changes in osteoarthritis.
Articular cartilage adalah hyaline cartilage yang nempel ke tulang dan tulang dibawahnya disebut subchondral.
Fungsinya adalah shock absorber/shock breaker, lubrication, and joint protection. Cartilage itu avascular dan dapat
nutrisi dari synovial fluid
Osteoarthritis, the slow progressive degeneration of articular cartilage, is the most common joint disease. It may be
caused by persistent and abnormally high loads on the joint surfaces, which initially result in the loss of proteoglycans
and chondrocytes from the articulating surface of the cartilage. Subsequently, the cartilage may crack (fibrillate), erode
and expose the underlying bone.
Articular cartilage, which makes possible the painless, low-friction movement of synovial joints, consists of a sparsely
distributed population of highly specialized cells called chondrocytes that are embedded within a matrix and provide
articular cartilage with remarkable mechanical properties. Chondrocytes form the tissue matrix macromolecular
framework from three classes of molecules: collagens, proteoglycans, and noncollagenous proteins. The matrix protects
the cells from injury resulting from normal joint use, determines the types and concentrations of molecules that reach
the cells, acts as a mechanical signal transducer for the cells, and helps maintain the chondrocyte phenotype.
Throughout life, articular cartilage undergoes internal remodeling as the cells replace matrix macromolecules lost
through degradation. 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.
4. Describe articular cartilage lubrication and healing.
Lubrication and Wear
The predominant method of lubrication of articular cartilage during joint motion is elastohydrodynamic lubrication. This
occurs when pressure in the fluid film deforms the articular surface, increasing the surface area and reducing escape of
fluid from between the surfaces as they glide over each other. Other methods of lubrication include boundary
lubrication (in which a lubricating glycoprotein prevents direct surface contact of the articulating surfaces), boosted
lubrication (where the solvent part of the lubricant enters the articular cartilage which leaves the hyaluronic acid
complxes acting as a lubricant) and weeping lubrication (which describes the ability of articular cartilage to exude or
imbibe fluid as the joint surfaces glide over each other providing self lubrication). The efficiency of these lubrication
processes means that wear in synovial joints is minimal.
Immobilization and Response to Healing
Articular cartilage requires physiologic stress (e.g., cyclical compression) to maintain its unique environment as a strong,
tough, fatigue-resistant, permeable, and low friction tissue.The biochemical components of proteoglycans or
glycosaminoglycans (GAGs), chondrocytes, matrix-molecules, and collagen significantly contribute to its structure,
composition, and mechanical properties.
Just as collagen is varied and distinct among the zones of articular cartilage, so are proteoglycans distributed in
different concentrations between zones. Because these proteoglycan molecules—including chondroitin sulfate, keratan
sulfate, and dermatan sulfate—bind and attract water (hydrophilic), their concentration and distribution among zones
influence the various mechanical wear characteristics of articular cartilage. The removal of normal physiologic loading,
unloading, and joint motion have profoundly negative effects on the biochemical and mechanical characteristics of
articular cartilage.
The significance of articular cartilage atrophy and degeneration is related to the magnitude and duration of
immobilization. Joint contact surfaces suffer greater degenerative changes than noncontact areas of articular cartilage.
5. Explain the role of proteoglycans and collagen and the changes in cartilage with disease and aging.
Proteoglycan 􀃆 protein yang ditempel oleh glycan; satu subunit disebut aggrecan; membantu membentuk struktur
cartilage dan memberi properti shock absorber.
Joint cartilage consists of cells embedded in a matrix of fibrous collagen within a concentrated water-proteoglycan gel.
The integrity of this matrix is crucial for the biomechanical properties of the joint cartilage. The different components of
the matrix are synthesized and degraded by the cartilage cells, a process regulated by the amount of mechanical stress
applied to the chondrocytes as well as by peptide factors and hormones present in synovial fluid. The proteoglycans are
large macromolecules consisting of a protein core to which are attached multiple chains of glycosaminoglycans and
oligosaccharides. During normal and pathological turnover, degradation products are released to the synovial fluid and
to the circulation. Newly developed assays allow the sensitive and specific detection of these fragments in joint fluid and
serum.
6. Describe the anatomy of the knee joint. (notes)

The knee joint is one of the strongest and most important joints in the human body. It allows the lower leg to
move relative to the thigh while supporting the body’s weight. Movements at the knee joint are essential to
many everyday activities, including walking, running, sitting and standing.

The knee, also known as the tibiofemoral joint, is a synovial hinge joint formed between three bones: the femur, tibia, and
patella. Two rounded, convex processes (known as condyles) on the distal end of the femur meet two rounded, concave
condyles at the proximal end of the tibia. The patella lies in front of the femur on the anterior surface of the knee
with its smooth joint-forming processes on its posterior surface facing the femur.

The joint-forming surfaces of each bone are covered in a thin layer of hyaline cartilage that gives them an
extremely smooth surface and protects the underlying bone from damage. Between the femur and tibia is a
figure-eight-shaped layer of tough, rubbery fibrocartilage known as the meniscus. The meniscus acts as a shock
absorber inside the knee to prevent the collision of the leg bones during strenuous activities such as running and
jumping.
As with all synovial joints, a joint capsule surrounds the bones of the knee to provide strength and lubrication.
The outer layer of the capsule is made of fibrous connective tissue continuous with the ligaments of the knee to
hold the joint in place. Oily synovial fluid is produced by the synovial membrane that lines the joint capsule and
fills the hollow space between the bones, lubricating the knee to reduce friction and wear.

Many strong ligaments surround the joint capsule of the knee to reinforce its structure and hold its bones in the
proper alignment. On the anterior surface of the knee, the patella is held in place by the patellar ligament, which
extends from the inferior border of the patella to the tibial tuberosity of the tibia. Posteriorly, the oblique
popliteal ligament and arcuate popliteal ligament join the femur to the tibia and fibula of the lower leg. Along
the medial side of the knee, the medial collateral ligament (MCL) connects the medial side of the femur to the
tibia and prevents forces applied to the lateral side of the knee from moving the knee medially. Likewise, the
lateral collateral ligament (LCL) binds the lateral side of the femur to the fibula and prevents forces applied to
the medial side of the knee from moving the knee laterally.

Two internal ligaments — the anterior and posterior cruciate ligaments — also help to maintain the proper
alignment of the knee. The anterior cruciate ligament (ACL) is the most anterior of these internal ligaments and
extends obliquely from the inner surface of the lateral condyle of the femur to the anterior intercondylar space
of the tibia. The ACL plays an important role in preventing hyperextension of the knee by limiting the anterior
movement of the tibia. Directly behind the ACL is the posterior cruciate ligament (PCL), which extends
obliquely from the inner surface of the medial condyle of the femur to the posterior intercondylar space of the
tibia. The PCL prevents the posterior movement of the tibia relative to the femur.

In addition to the joint capsule and ligaments that support the knee, there are also several important structures
surrounding the knee that help cushion and protect the joint from friction and outside forces. Small pockets of
synovial fluid, known as bursae, surround the knee to reduce the friction from movement of tendons across the
surface of the joint. Several of these bursae, including the suprapatellar bursa, are instrumental in the reduction
of friction between the patella and femur. Pockets of adipose tissue around the knee, known as articular fat
pads, help to cushion the knee from external stress. The largest of these pads, the infrapatellar fat pad, absorbs
shock to the anterior surface of the knee and cushions the patellar ligament as it moves with the patella during
flexion and extension of the knee.

As the knee is a synovial hinge joint, its function is to permit the flexion and extension of the lower leg relative
to the thigh. The range of motion of the knee is limited by the anatomy of the bones and ligaments, but allows
around 120 degrees of flexion. A special characteristic of the knee that differentiates it from other hinge joints is
that it allows a small degree of medial and lateral rotation when it is moderately flexed.

7. Explain the anatomy, physiology and biomechanics of the cruciate ligaments and menisci.
Cruciate ligaments of the knee are the anterior cruciate ligament (ACL) and the posterior cruciate ligaments (PCL).
These ligaments are two strong, rounded bands that extend from the head of the tibia to the intercondyloid notch
of the femur. The ACL is lateral and the PCL is medial.

The ACL arises from the anteromedial aspect of the intercondylar area on the tibial
plateau and passes upwards and backwards to attach to the posteromedial aspect of the
lateral femoral condyle.

Like the posterior cruciate ligament, the ACL is intracapsular but extrasynovial.

The ACL consists of two components 4:

1. anteromedial bundle (AMB)

 o attaches to roof of intercondylar notch
2. posterolateral bundle (PLB)
o more vertically orientated, and slightly shorter
o attaches to wall of intercondylar notch

Blood supply
 arterial: middle genicular artery

Function
The ACL functions to prevent posterior translation of the femur on the tibia (or anterior
displacement of the tibia) during flexion-extension of the knee. The AMB is responsible for the
posterior translation of the femur at 30 degrees flexion, and the PLB resists hyperextension
and prevents posterior translation of the femur in extension

Gross anatomy
The PCL attaches to the posterior intercondylar area and passes anterosuperiorly to insert
into the lateral surface of the medial femoral condyle.

When the knee is in extension, it makes an almost 90º turn as it passes anterosuperiorly.
The anterior cruciate ligament passes lateral to it and curves around it.

The PCL is intracapsular but extrasynovial and is approximately 13 mm in diameter. It

contains two fibre bundles named according to their relative attachments 1:

1. anterolateral
2. posteromedial

Function
During flexion, the anterolateral band becomes tight, whereas the posterolateral bundle
tightens during extension 1 and the PCL as a whole acts to resist anterior translation of the
femur on the tibia

The medial meniscus is the central band of cartilage attached to the tibia, or shinbone.
The band goes around the knee joint in a crescent-shaped path and is located between
the medial condyles of the shin and the femur, or thighbone. The medial condyles are
areas of these bones located on the inner sides of the knees.
The medial meniscus is the central band of cartilage attached to the tibia, or shinbone.
The band goes around the knee joint in a crescent-shaped path and is located between
the medial condyles of the shin and the femur, or thighbone. The medial condyles are
areas of these bones located on the inner sides of the knees.

The medial meniscus is often injured when the knee is twisted or sprained with sudden
force. It is less mobile than the lateral meniscus because it is firmly attached to the tibial
collateral ligament. External rotation (rotating the knee outward) puts the most strain on
the meniscus, while inward (internal) rotation is the least strenuous.

The most common medial meniscus injury is tearing. Intense swelling and pain is expected
during the first 24 hours following this injury. Symptoms of a torn medial meniscus include
being unable to extend the leg, feeling best when the knee is bent, developing gradual
pain after stressing the knees, and swelling in the knee region. The medial meniscus may
need to be surgically repaired if the tear is above Grade 2 (on a 1 to 4 scale). Common
surgery types include arthroscopic repair, partial meniscectomy, and total meniscectomy.
Arthroscopic repair is a form of minimally invasive joint surgery. Partial meniscectomy
involves a partial removal of the meniscus, as opposed to the full removal that occurs
during total meniscectomy.

8. Describe fibrocartilage and menisci.

Fibrocartilage
Fibrocartilage has a dense arrangement of cartilage fibers that are arranged in an orderly manner. Numerous chondrocytes are located
within their lacunae and are spaced between the fibers. Fibrocartilage is primarily composed of type I collagen, and is located in areas
like the intervertebral discs and the pubic symphysis. Note that the chondrocytes are surrounded by a matrix which helps differentiate
fibrocartilage from dense connective tissue.
9. Describe the structure and function of ligaments and tendons.

Tendon termasuk apoeurosis karena dia merupakan perpanjangan dari otot untuk
dijadikan insertio ke tulang. Tendon juga memiliki pembuluh darah lebih sedikit dan
jaringan kontraktur lebih sedikit. Ligament  bone to bone (ibaratkan selotip) dan terdiri atas jaringan ikat
padat
10. Understand the pathophysiology of osteoarthritis. (notes)
11. Describe appropriate management options for symptomatic osteoarthritis (non surgical and surgical). (notes)